运动对线粒体生物发生及其信号转导机制的研究
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摘要
耐力运动带来骨骼肌脂肪酸氧化和线粒体密度增加,且变化具有高度特异性,其确切的调节分子机制还有待研究。线粒体发生过程需要核DNA与线粒体DNA(mtDNA)共同协调表达,调节基因组间协调表达及mtDNA转录和复制的信号通路还不是特别清楚。运动刺激线粒体生物发生,其中一个重要的生物学过程就是活性氧自由基(ROS)的产生,导致细胞氧化还原状态的变化。长期适度运动产生适量的ROS可能在运动引起的线粒体发生中发挥关键作用。另有研究提示哺乳动物雷帕霉素靶蛋白(mTOR)信号通路与线粒体功能之间密切联系,且mTOR通路受到细胞氧化还原状态的调节,这也许是mTOR感受营养等条件刺激及与线粒体活性间联系的潜在机制。
运动对mTOR信号的诱导作用还不完全清楚。有人认为类似耐力运动的刺激选择性激活单磷酸腺苷激活蛋白激酶(AMPK)/过氧化物酶增殖激活受体γ-辅助激活因子-1α(PGC-1α)信号通路,抗阻训练则激活蛋白激酶B(Akt)/mTOR通路,且有氧运动后激活的AMPK/PGC-1α信号可能是mTOR信号通路抑制的原因之一。但还存在许多矛盾的结论,如抗阻运动后AMPK信号通路激活,而长期有氧运动激活Akt/mTOR信号通路等。总之,目前对于运动后AMPK/PGC-1α和Akt/mTOR信号通路激活情况的认识还相当欠缺,而除了AMPK/PGC-1α信号通路之外,Akt/mTOR信号通路在线粒体发生过程中的作用也相当值得研究。
长期训练后的适应性变化被认为源自每次急性运动后暂时性变化效应的累积。目前,对于急性运动后基因特异性转录激活的认识越来越多。这种激活,在某种水平上,起到恢复和维持运动后骨骼肌稳态的作用,同时也是长期训练后骨骼肌适应性变化的基础。PGC-1α被认为在骨骼肌适应性变化的过程中发挥关键性作用。PGC-1α具有结合和影响很多转录因子的作用,调节特定细胞进程;PGC-1α还辅助激活过氧化物酶增殖体激活受体(PPAR)α和γ,调节脂肪酸摄取和β-氧化,及通过对解偶联蛋白(UCPs)的转录调节而调节解偶联呼吸;此外,PCG-1α和核受体相互作用,包括核呼吸因子(NRFs),参与多种核编码基因和线粒体转录因子A(Tfam)等的表达。转录因子Tfam、线粒体转录特异因子B1(TFB1M)及线粒体转录特异因子B2(TFB2M)与NRF-1和NRF-2关系密切,共同合作负责调节核及mtDNA编码的转录因子的表达,确保线粒体的发生。运动可以激活多种信号分了,包括AMPK,促进PGC-1α及其下游信号的表达。此外,目前研究已发现,除了PGC-1α外,耐力运动导致多种与线粒体发生和代谢有关的基因表达变化,如NRFs、Tfam、PPARα、丙酮酸脱氢酶激酶(PDK4)、脂蛋白酯酶(LPL)、肉毒碱棕榈酰转移酶Ⅰ(CPTⅠ)等。
本研究的目的在于:1)探讨不同运动强度(中等强度和大强度运动)对于线粒体发生的不同影响;2)探讨mTOR信号通路在运动介导的线粒体发生中的作用;3)探讨两种急性耐力运动后骨骼肌线粒体生物发生和脂肪酸氧化相关信号基因表达的变化。
一单纯运动干预和运动联合mTOR信号抑制剂雷帕霉素(RPM)干预对大鼠线粒体生物发生的影响
方法:SD大鼠42只,所有大鼠适应性饲养一周后,进行适应性训练3天。此后进行随机分组。第一批大鼠18只实施单纯运动干预研究,分为3组:安静组(C组)、中等强度运动组(M组)和高强度运动组(H组);第二批大鼠24只实施运动联合RPM干预研究,分成4组:安静组(C组)、单纯RPM注射组(R组)、单纯中等强度运动组(M组)和中等强度运动加RPM注射组(MR组)。每组大鼠数量均为6只。
第一批大鼠M组和H组分别在1周渐增强度训练后继续2周不同强度的跑台运动,每周5次,每次1小时。C组不参加运动训练。末次运动结束48小时候处死大鼠,取骨骼肌提取线粒体检测ROS水平,同时保存部分骨骼肌样本留待检测线粒体呼吸链酶复合物(complexⅠ,ⅡandⅣ)蛋白表达及mtDNA和细胞色素氧化酶(COX)Ⅳ基因表达水平。
第二批大鼠中M组和MR组进行1周渐增强度训练后继续2周中等强度跑台运动,每周5次,每次1小时,C组和R组不参加运动训练。同时,R组和MR组注射RPM(2mg/kg体重),每周5次,每次注射均在运动前1小时完成。末次运动结束后48小时处死大鼠,取骨骼肌、脑和肝脏三种组织,分别提取线粒体检测ROS生成水平和线粒体呼吸链酶复合物(complexⅠ)活性同时冷冻部分骨骼肌样本留待检测线粒体呼吸链复合物(complexⅠ,ⅡandⅣ)蛋白表达、相关信号蛋白PGC-1α、NRF-2和磷酸化Akt(P-Ser473-Akt)表达及mtDNA和COXⅣ基因表达水平。
结果:1)第一批大鼠各组(C组、M组及H组)骨骼肌线粒体ROS及第二批大鼠各组(C组、R组、M组和MR组)骨骼肌、脑和肝脏组织线粒体ROS的生成水平相似,无统计学显著差异(P＞0.05)。
2)运动联合RPM干预研究中大鼠脑、肝脏和骨骼肌线粒体M组的ComplexⅠ活性均显著增加(P＜0.05)。肝脏线粒体MR组也出现了同样的变化。脑线粒体中R组ComplexⅠ活性显著下降,且M组与R组比较,存在显著差异(P＜0.05)。
3)单纯运动干预研究中,ComplexⅠ蛋白表达在M组和H组显著增加,ComplexⅡ在各组没有显著变化,ComplexⅣ表现出和ComplexⅠ相似的增加趋势,但是无统计学显著差异。
4)运动联合RPM干预研究中,ComplexⅠ在M组及MR组显著增加,ComplexⅡ在所有组间无显著变化,ComplexⅣ在M组和MR组也表现出增加的趋势,但是无统计学显著差异。
5)运动联合RPM干预研究中,P-Ser473-Akt蛋白水平在M组和MR组出现同样的显著增加,PGC-1α和NRF-2蛋白水平在M组显著增加。
6)mtDNA在单纯运动干预研究没有出现显著性变化,但M组出现增加的趋势(P=-0.083),在运动联合RPM干预研究中的各组同样没有出现显著性变化,但是M组和MR组均出现增加趋势(P分别为0.08和0.095)。COXⅣ在单纯运动干预研究的M组显著增加,且和H组比较有显著差异;在运动联合RPM干预研究中,M组和MR组均显著增加。
结论:1)ROS在线粒体发生过程中发挥重要的第二信使作用,但是长期运动训练后ROS生成可能与急性运动后的变化有所不同。2周运动后安静状态下线粒体ROS生成并没有显著变化,此外,RPM单独使用或者联合运动干预也不会影响安静状态下线粒体ROS生成。
2)运动训练增加ComplexⅠ蛋白含量和活性等,增强线粒体呼吸和氧化功能。RPM抑制了脑线粒体ComplexⅠ活性及运动对ComplexⅠ活性的激活,但是在肝脏和骨骼肌组织中没有出现这一现象,提示不同组织对RPM反应的敏感程度不同。对于其它线粒体呼吸链复合物如ComplexⅡ和Ⅳ蛋白的表达,可能需要更长运动周期或者不同运动方式促使其变化。
3)耐力运动激活Akt,从而有可能激活mTOR信号通路,且RPM的使用并不能阻止运动对Akt的激活。
4)中等强度运动通过促进骨骼肌PGC-1α和NRF2蛋白表达增加促进线粒体发牛,2周后COXⅣ基因表达显著增加,mtDNA呈上升趋势,而RPM在一定程度上抑制了运动介导的线粒体发生。
二两种自行车运动对人骨骼肌线粒体发生及脂肪酸代谢相关信号基因表达的影响
方法:选取了9名无规律运动训练史的健康受试者,采用两种相同强度(60%VO_(2max))和持续时间(90min)但不同形式的运动,即持续性(Con)和间歇性(In)自行车运动,分别检测运动前(Pre)、运动后即刻(Post)及运动后3小时恢复期(3 hs Post)气体代谢、血液生化学指标及以PGC-1α为核心的一系列转录因子基因表达的变化。持续性自行车运动中,整个过程运动强度保持恒定的60%VO_(2max)的水平;间歇性自行车运动,运动强度为120%VO_(2max)持续12秒和20%VO_(2max)持续18秒轮流交替。两种运动强度相等,持续时间均为90分钟。两次运动相隔至少两周时间进行。运动前、运动中每30分钟各收集呼出气体一次分析气体代谢指标。血标本和肌肉标本分别在运动前、运动结束即刻和运动后3小时获取,用于检测血糖、血乳酸和游离脂肪酸(FFA)浓度及线粒体发生和脂肪酸代谢相关的多种信号基因的表达。
结果:1)气体代谢指标RQ、VO_2(L/min)、VO_2(ml/min.kg weight)、Vent、Vent/VO_2,及HR、RPE等,在In组和Con组均极为相似和接近。
2)血乳酸在In和Con组的Post显著升高(P＜0.05),在3 hs Post时恢复到安静水平;FFA在In和Con组的Post和3 hs Post均显著升高(P＜0.05)(在In组和Con组分别升高了2.7和3.3倍),且Post和3 hs Post的FFA浓度十分相似和接近;Glucose在In和Con组的Post(P＜0.01)和3 hs Post均显著降低(P＜0.05)。
3)Con组和In组,PGC-1αmRNA和PRCmRNA在Post均有增加的趋势(P＞0.05),但直至3 hs Post才显著升高,且3 hs Post与Post间具有显著差异。PGC-1α在Con组和In组3 hs Post分别升高了4.6倍和6.9倍;PRC在Con组和In组3 hs Post分别升高了3.0倍和3.3倍。PGC-1βmRNA在Con组和In组都没有发现显著性差异。
4)NRF-1 mRNA在Con和In组均显著下降。在Con中Post和3 hs Post时间点NRF-1 mRNA分别下降了22%(P＜0.05)和34%(P＜0.05);在In组Post和3hs Post时间点分别下降了25%(P＜0.05)和9%(P＞0.05)。NRF-2只在In组中出现显著下降,Post和3 hs Post分别下降了33%(P＜0.05)利26%(P＜0.05);在Con组有下降的趋势(Post和3 hs Post分别下降了14%和13%),但是没有达到统计学差异。与NRF-1和NRF-2关系及其密切,负责mtDNA转录和复制的调节因子:Tfam、TFBlM和TFB2M,在Con和In组运动前后均没有发生显著性变化。
5)AMPKα1 mRNA在Con和In组运动前后没有发生显著性改变,但是AMPKα2 mRNA在Con和In组运动后均显著降低(Con组和In组3 hs Post分别降低了36%和43%),且3 hs Post与Post比较,均具有显著差异(P＜0.05)。
6)PPARs家族的3个成员中PPARα和PPARβmRNA在Con和In组中均没有发生显著性变化;PPARγmRNA只在Con组的3 hs Post显著降低(下降了23%),In组没有发生显著性变化。3个成员在运动后的变化之间没有发现显著的相关关系。
7)PDK4表现出与PGC-1α及PRC十分相似的变化特点。Con组和In组Post均具有升高趋势(3.0倍和2.2倍),但无显著性差异,3 hs Post显著上升(16倍和6.7倍),且与运动后即刻比较显著差异。CPTⅠβmRNA在运动后出现下降的趋势。在Con组和In组分别下降了18%和28%(Post)及41%和21%(3 hsPost)。但是,只有Con组3 hs Post(下降41%)具有统计学显著差异。LPLmRNA在两组运动后表现出非常相似的变化趋势,Post下降(Con组和In组分别下降了9%和23%),3 hs Post稍有所升高(Con组和In组分别上升了1.06和1.14倍),但是无统计学显著差异。
8)PGC-1α和PGC-1βmRNA在Con组和In组中Post和3 hs Post的变化均具有显著的正相关关系。TFB1M和TFB2M mRNA在Con组和In组中3 hs PostmRNA的变化均具有显著正相关关系(P分别＜0.01和＜0.001),但是在Con组和In组Post的变化却没有出现显著相关关系。
结论:1)两种相同强度、相同时间,但不同形式自行车运动(持续性和间歇性)运动对机体造成相似的应激,对线粒体发生和脂肪酸代谢相关信号基因表达的影响间也无显著差异。
2)运动对PGC-1家族成员的调节有所不同。90分钟中等强度(60%VO_(2max))自行车运动后,PGC-1α、PRC mRNA在运动后3小时均显著增加,而PGC-1βmRNA没有变化。PDK4 mRNA的变化和PGC-1α及PRC十分相似。这些都提示急性运动可能通过激活重要的相关转录因子等促进线粒体发生和脂肪酸氧化等。
3)90分钟中等强度(60%VO_(2max))自行车运动后,NRF-1、NRF-2、AMPKα2、PPARγ、CPT-ⅠβmRNA等出现了不同程度的下降,这说明急性运动后某些基因可能受到抑制,或者至少这些基因的变化不是简单的运动后升高变化,可能存在先抑制后激活等变化特点,另外急性运动后机体的反应和长期运动带来的变化可能有所不同,甚至完全相反。
全文总结:1)2周中等强度和高强度运动虽然没有改变安静状态下线粒体ROS生成水平,但是显著增加了线粒体呼吸链复合物活性和蛋白表达。中等强度运动促进线粒体发生,与线粒体发生相关的信号蛋白P-Ser473-Akt、PGC-1α及NRF-2蛋白表达及COXⅣ基因表达显著增加,mtDNA基因表达也呈增加趋势。
2)气体代谢指标、血乳酸、FFA和血糖等指标变化在90分钟中等强度(60%VO_(2max))持续性和间歇性自行车运动干预下变化十分接近,且多种线粒体发生及代谢相关的信号基因变化也十分相似。
3)90分钟中等强度(60%VO_(2max))持续性和间歇性自行车运动后PGC-1α、PRC和PDK4均在运动后即刻呈增加趋势,结束后3小时显著升高;PGC-1β无显著变化;NRF-1、NRF-2、AMPKα2、PPARγ、CPT-ⅠβmRNA等出现了不同程度的下降,提示急性运动后线粒体发生和代谢相关的基因激活从而促进线粒体发生和增加脂肪酸动员和氧化供能,但是某些基因可能受到抑制,或者至少这些基因的变化不是简单的运动后升高,可能存在先抑制后激活等其它变化特点,也提示急性运动后机体的反应和长期运动带来的变化可能有所不同,甚至完全相反。
Skeletal muscle exhibits remarkable adaptive capabilities in response to a number of physiological and pathophysiological conditions.Chronic contractile activities induce mitochondrial biogenesis and increase fatty acids oxidation in skeletal muscle.These adaptations are highly specific and dependent upon the type of exercise(i.e.)resistance vs endurance)as well as its frequency,intensity and duration.A coordinated alteration in the expression of a variety of nuclear DNA and mitochondrial DNA(mtDNA)gene is needed for the adaptations.The molecular mechanism still remains unclear.One of the most important biological processes is ROS production in the exercise-induced mitochondrial biogenesis which changes the redox state of cell.Acute exercise may be a stress for the body because of the increased ROS production.The ROS induced by long term moderate exercise may play critical role in mitochondrial biogenesis.Studies suggest mTOR signal is associated with mitochondrial function and is regulated by the redox state of cell.This may be the potential mechanism links mitochondrial activity to mTOR under regulation of nutrition and other physiological and pathophysiological conditions.
The effect of exercise on mTOR signal is not clear.It is thought that endurance exercise and resistance exercise can selectively activate either AMPK/PGC-1αor Akt/mTOR signaling,respectively and the activated AMPK/PGC-1αmay inhibit Akt/mTOR signaling.However,there are some contradict findings.More delicately designed study is needed to make clear about the effects of exercise on AMPK/PGC-1αand Akt/mTOR signaling and it is worth to probe the role of AMPK/PGC-1αas well as Akt/mTOR signal pathway in mitochondrial biogenesis and metabolism.
There is a growing understanding that gene-specific transcriptional activation during and after a bout of exercise is involved,to some extent,in reestablishing homeostasis in skeletal muscle after the exercise bout,as well as contributing to the skeletal muscle adaptations that occur in response to exercise training.PGC-1αis thought to play a pivotal role in these processes.The positive effects of PGC-1αon transcription are thought to be mediated by its ability to bind to specific transcription factors recruit additional coactivators,thereby enhancing the overall efficiency of the transcriptional machinery.PGC-1αcan influence fatty acids oxidation andβ-oxidation through co- activating PPARαandγand influence uncoupling respiration by regulating UCPs transcription.NRF-1,as a strong coactivator of PGC-1α,leads to increased levels of several nuclear-encoded mitochondrial proteins,including Tfam,provokes an increase in mtDNA transcription and replication.Tfam,together with TFB1M and TFB2M,which is closely associated with NRFs,is responsible for the expression of various transcription factors coded by nuclear DNA and mtDNA.Although the entire transcriptional response to endurance exercise has not been currently demonstrated,a single bout of endurance exercise has been shown to increase mRNA expression of a growing number of genes, the majority of which are involved in mitochondrial biogenesis and fatty acids metabolism,such as NRFs,Tfam,PPARα,PDK4,LPL and CPTⅠ.
The purposes of the current study were as follows.One was to test the effects of different intensities of exercise,which included moderate intensity and high intensity,on mitochondrial biogenesis and to test the role of mTOR signal in the exercise-induced mitochondrial biogenesis.The second purpose was to test the effects of two kinds of acute cycling exercise on the expression of various transcription factors which related to mitochondrial biogenesis and fatty acids oxidation.
1 The effects of exercise and exercise combined with mTOR inhibitor on rat mitochondrial biogenesis.
Method:Following one week of adaptive feeding,24 SD rats underwent adaptive training for 3 days.After this,they were divided into different groups.The first 18 rats were divided into 3 groups which included control group(C),moderate intensity exercise group(M)and high intensity exercise group(H).The second 24 rats were divided into 4 groups which include control(C),RPM group(R),moderate intensity exercise group(M) and moderate intensity exercise combined with RPM group(MR).There are 6 rats in each group.
For the first 18 rats,following 1 week of progressed increasing intensity exercise,M and H groups were trained on the treadmill under moderate and high intensity for 1 hour every time and 5 times a week which last for 2 weeks and C group didn't do any exercise. They were killed 48 hours after the last time exercise.Mitochondria were isolated from skeletal muscle and were used for testing ROS production.The other part of skeletal muscle were saved in -80℃for testing complexⅠ,ⅡandⅣproteins level as well as mtDNA and COXⅣgene expression later.
For the second 24 rats,following 1 week of progressed increasing intensity exercise, M and MR groups were trained on the treadmill with moderate and high intensity for 1 hour every time and 5 times a week which last for 2 weeks and C and R groups didn't do any exercise.R and MR groups were injected with RPM(2mg/kg mass)for 5 times a week and the injection was carried out 1 hour before the beginning of exercise every time. All the rats were killed 48 hours after the last time exercise.Mitochondria were isolated from skeletal muscle,brain and liver which were used for testing ROS production and complexⅠactivity.The other part of skeletal muscle were saved in -80℃for testing complexⅠ,Ⅱ,Ⅳproteins level and P-Ser-473 Akt,PGC-1αand NRF-2 protein level as well as mtDNA and COXⅣgene expression.
Results:1)There was no significant change of ROS production at rest among C,M and H group in the first 18 rats and among C,R,M and MR groups in the second 24 rats (P＞0.05).
2)ComplexⅠactivity was tested only in the second 24 rats.It increased significantly in M group from mitochondria isolated from all three tissues(brain,liver and skeletal)in the second 24 rats(P＜0.05).The same change also appeared in MR group from live mitochondria.ComplexⅠactivity decreased significantly in R group from brain mitochondria and there was significant difference between M and R groups(P＜0.05).
3)ComplexⅠprotein expression increased significantly in M and H groups in the first 18 rats.ComplexⅡprotein didn't change among three groups and ComplexⅣprotein had the trend to increase in M and H group but without significance.
4)ComplexⅠprotein expression increased in M and MR groups in the second 24 rats.ComplexⅡhad no change among four groups and Complexiv had trend to increase in M and MR groups,but without significance.
5)P-Ser473-Akt protein expression increased significantly in M and MR groups and PGC-1αand NRF-2 protein expression increased significantly only in M group.
6)mtDNA expression showed trend to increase in M group(P=0.083)in the first 18 rats and in the M and MR groups(P=0.08,0.095)in the second 24 rats.COXⅣgene expression increased significantly in M group and was significantly different with H group in the first 18 rats and also increased significantly in M and MR groups in the second 24 rats.
Conclusions:1)ROS may play an important role in mitochondrial biogenesis. However,there may be difference between the effects of acute and long term exercise on ROS production.Mitochondrial ROS production at rest didn't change either after 2 weeks of exercise or exercise combined with RPM injection.
2)Exercise training increased ComplexⅠactivity in mitochondria from skeletal muscle,brain and liver as well as ComplexⅠprotein expression in skeletal muscle.RPM inhibited ComplexⅠactivity in brain tissue but not in skeletal and liver.2 weeks of exercise didn't change ComplexⅡandⅣprotein level which suggested that longer or different style of exercise might be needed to stimulate their changes.
3)Endurance training activated Akt/mTOR signaling by increasing Akt phosphorylation in a RPM independent way.
4)Moderate intensity exercise induced mitochondrial biogenesis by stimulating the protein expression of PGC-1αand NRF2.RPM could inhibit the effects and the increase in COXⅣand mtDNA gene expression induced by exercise to some extent.
2 The effects of two kinds of cycling exercise on human skeletal muscle mitochondrial biogenesis and fatty acids oxidation and the related signal gene expression.
Method:Nine healthy subjects who didn't exercise regularly for at least 6 months before the test were recruited.Two different styles of cycling exercise(continuous and intermittent)with the same intensity(60%VO_(2max))and duration time(90min)were carried out on these 9 subjects on separate day.For continuous exercise(Con),the intensity was kept at constant 60%VO_(2max)level for 90min and for the intermittent exercise(In),the intensity is consist of 120%VO_(2max)for 12sec and 20%VO_(2max)for 18sec and repeated like this for 90min.The expired gas was collected during exercise which used for analyzing the gas metabolism.Blood and muscle sample were taken before exercise(Pre),immediately after exercise(Post)and 3 hours after exercise(3hs Post) which used for testing fatty acids(FFA),lactate and glucose as well as the gene expression of various transcription factors who closely related to mitochondrial biogenesis and fatty acids can be tested.
Results:1)Metabolism indexes,such as RQ,VO_2(L/min),VO_2(ml/min.kg weight), Vent,Vent/VO_2,and HR,RPE etc.were very close to each other in In and Con groups.
2)Lactate increased significantly at Post in In and Con(P＜0.05)and returned to base level at 3 hs Post.FFA increased significantly at Post and 3 hs Post in Con and In groups(P＜0.05).Glucose decreased significantly in In and Con at Post(P＜0.01)and 3 hs Post(P＜0.05).
3)PGC-1αand PRC mRNA increased after exercise but only show significant 3 hs Post in Con and In Groups and there was significant difference between Post and 3 hs Post.PGC-1αmRNA increased 4.6 and 6.9 folds 3 hs Post in Con and In respectively and PRC increased 3.0 and 3.3 folds.There was no significant change of PGC-1βmRNA.
4)NRF-1 mRNA decreased in Con and In groups.NRF-1 mRNA decreased 22%(P＜0.05)and 34%(P＜0.05)at Post and 3 hs Post in Con group and 25%(P＜0.05)and 9%(P＞0.05)in In group respectively.NRF-2 mRNA decreased significantly only in In group which decreased 33%(P＜0.05)and 26%(P＜0.05)at Post and 3 hs Post.It showed trend to decrease but without significance(decreased 14%and 13%at Post and 3 hs Post respectively)in Con group.No significant change happened on Tfam,TFB1M and TFB2M mRNA in Con and In groups.
5)AMPKα1 didn't change but AMPKα2 decreased significantly at 3 hs Post in Con and In groups(36%and 43%in Con and In group respectively)and both were different with Post(P＜0.05)。
6)PPARαand PPARβmRNA didn't change significantly while PPARγdecreased significantly 3 hs Post in Con(23%)not In group.There is no correlation between the expression of three PPARs subunits.
7)PDK4 mRNA showed similar change with PGC-1αand PRC and increased 3.0 and 2.2 folds at Post(P＞0.05)and increased 16 and 6.7 folds 3 hs Post in Con and In groups respectively(P＜0.05).CPTⅠβmRNA decreased at Post but only show significance at 3 hs Post in Con group.LPL mRNA showed trend to decrease at Post and increase at 3 hs Post and both of them had no significance.
8)The expression of PGC-1αmRNA was positively correlated with PGC-1βin Con and In groups both at Post and 3 hs Post.The positive correlation also existed between TFB1M and TFB2M mRNA in Con and In groups at 3 hs Post(P＜0.01,＜0.001 respectively)but not at Post.
Conclusions:1)Two kinds of cycling exercise(continuous and intermittent)with same intensity(60%VO_(2max))and duration time(90min)caused similar stress and similar changes in the gene expression of transcription factors related to mitochondrial biogenesis and fatty acids oxidation.
2)The regulations of PGC-1 family members by exercise were different.90 min moderate intensity(60%VO_(2max))cycling caused significant increase in PGC-1αand PRC mRNA but no change in PGC-1βmRNA.PDK4 mRNA showed similar change with PGC-1αand PRC.These suggested that acute exercise may promote mitochondrial biogenesis and fatty acids oxidation by activating important transcription factors involved.
3)NRF-1、NRF-2、AMPKα2、PPARγand CPT-ⅠβmRNA decreased after 90 min moderate intensity(60%VO_(2max))cycling.This suggested that some genes were inhibited after acute exercise or at least were inhibited at some time points after acute exercise.It could not be excluded that they would be activated after short time inhibition. It also suggested that the change after acute exercise might be totally different with that after long term exercise.
Summary:1)2 weeks of moderate and high intensity exercise enhanced mitochondrial respiration chain complexes activity and protein expression though had no effect on ROS production at rest.Moderate exercise promoted mitochondrial biogenesis as evidenced by significantly increased Akt,PGC-1αand NRF-2 protein expression, COXⅣ,mtDNA gene expression.
2)Two kinds of cycling exercise(continuous and intermittent)with same intensity (60%VO_(2max))and duration time(90min)caused similar stress to body and similar changes in FFA,Lactate and Glucose as well as the gene expression of transcription factors related to mitochondrial biogenesis and fatty acids oxidation.
3)PGC-1α,PRC and PDK4 mRNA increased significantly after 90 min moderate intensity(60%VO_(2mxa))cycling,but PGC-1βmRNA has no change and NRF-1,NRF-2, AMPKα2,PPARγand CPT-ⅠβmRNA decreased significantly.These suggested that mitochondrial biogenesis and fatty acid mobilization and oxidation were induced by a bout of endurance exercise while some other related genes were inhibited or at least inhibited temperally.It could not be excluded that these genes would be activated after short time inhibition.The change after acute exercise might be quite different with that after long term exercise.
运动对mTOR信号的诱导作用还不完全清楚。有人认为类似耐力运动的刺激选择性激活单磷酸腺苷激活蛋白激酶(AMPK)/过氧化物酶增殖激活受体γ-辅助激活因子-1α(PGC-1α)信号通路,抗阻训练则激活蛋白激酶B(Akt)/mTOR通路,且有氧运动后激活的AMPK/PGC-1α信号可能是mTOR信号通路抑制的原因之一。但还存在许多矛盾的结论,如抗阻运动后AMPK信号通路激活,而长期有氧运动激活Akt/mTOR信号通路等。总之,目前对于运动后AMPK/PGC-1α和Akt/mTOR信号通路激活情况的认识还相当欠缺,而除了AMPK/PGC-1α信号通路之外,Akt/mTOR信号通路在线粒体发生过程中的作用也相当值得研究。
长期训练后的适应性变化被认为源自每次急性运动后暂时性变化效应的累积。目前,对于急性运动后基因特异性转录激活的认识越来越多。这种激活,在某种水平上,起到恢复和维持运动后骨骼肌稳态的作用,同时也是长期训练后骨骼肌适应性变化的基础。PGC-1α被认为在骨骼肌适应性变化的过程中发挥关键性作用。PGC-1α具有结合和影响很多转录因子的作用,调节特定细胞进程;PGC-1α还辅助激活过氧化物酶增殖体激活受体(PPAR)α和γ,调节脂肪酸摄取和β-氧化,及通过对解偶联蛋白(UCPs)的转录调节而调节解偶联呼吸;此外,PCG-1α和核受体相互作用,包括核呼吸因子(NRFs),参与多种核编码基因和线粒体转录因子A(Tfam)等的表达。转录因子Tfam、线粒体转录特异因子B1(TFB1M)及线粒体转录特异因子B2(TFB2M)与NRF-1和NRF-2关系密切,共同合作负责调节核及mtDNA编码的转录因子的表达,确保线粒体的发生。运动可以激活多种信号分了,包括AMPK,促进PGC-1α及其下游信号的表达。此外,目前研究已发现,除了PGC-1α外,耐力运动导致多种与线粒体发生和代谢有关的基因表达变化,如NRFs、Tfam、PPARα、丙酮酸脱氢酶激酶(PDK4)、脂蛋白酯酶(LPL)、肉毒碱棕榈酰转移酶Ⅰ(CPTⅠ)等。
本研究的目的在于:1)探讨不同运动强度(中等强度和大强度运动)对于线粒体发生的不同影响;2)探讨mTOR信号通路在运动介导的线粒体发生中的作用;3)探讨两种急性耐力运动后骨骼肌线粒体生物发生和脂肪酸氧化相关信号基因表达的变化。
一单纯运动干预和运动联合mTOR信号抑制剂雷帕霉素(RPM)干预对大鼠线粒体生物发生的影响
方法:SD大鼠42只,所有大鼠适应性饲养一周后,进行适应性训练3天。此后进行随机分组。第一批大鼠18只实施单纯运动干预研究,分为3组:安静组(C组)、中等强度运动组(M组)和高强度运动组(H组);第二批大鼠24只实施运动联合RPM干预研究,分成4组:安静组(C组)、单纯RPM注射组(R组)、单纯中等强度运动组(M组)和中等强度运动加RPM注射组(MR组)。每组大鼠数量均为6只。
第一批大鼠M组和H组分别在1周渐增强度训练后继续2周不同强度的跑台运动,每周5次,每次1小时。C组不参加运动训练。末次运动结束48小时候处死大鼠,取骨骼肌提取线粒体检测ROS水平,同时保存部分骨骼肌样本留待检测线粒体呼吸链酶复合物(complexⅠ,ⅡandⅣ)蛋白表达及mtDNA和细胞色素氧化酶(COX)Ⅳ基因表达水平。
第二批大鼠中M组和MR组进行1周渐增强度训练后继续2周中等强度跑台运动,每周5次,每次1小时,C组和R组不参加运动训练。同时,R组和MR组注射RPM(2mg/kg体重),每周5次,每次注射均在运动前1小时完成。末次运动结束后48小时处死大鼠,取骨骼肌、脑和肝脏三种组织,分别提取线粒体检测ROS生成水平和线粒体呼吸链酶复合物(complexⅠ)活性同时冷冻部分骨骼肌样本留待检测线粒体呼吸链复合物(complexⅠ,ⅡandⅣ)蛋白表达、相关信号蛋白PGC-1α、NRF-2和磷酸化Akt(P-Ser473-Akt)表达及mtDNA和COXⅣ基因表达水平。
结果:1)第一批大鼠各组(C组、M组及H组)骨骼肌线粒体ROS及第二批大鼠各组(C组、R组、M组和MR组)骨骼肌、脑和肝脏组织线粒体ROS的生成水平相似,无统计学显著差异(P＞0.05)。
2)运动联合RPM干预研究中大鼠脑、肝脏和骨骼肌线粒体M组的ComplexⅠ活性均显著增加(P＜0.05)。肝脏线粒体MR组也出现了同样的变化。脑线粒体中R组ComplexⅠ活性显著下降,且M组与R组比较,存在显著差异(P＜0.05)。
3)单纯运动干预研究中,ComplexⅠ蛋白表达在M组和H组显著增加,ComplexⅡ在各组没有显著变化,ComplexⅣ表现出和ComplexⅠ相似的增加趋势,但是无统计学显著差异。
4)运动联合RPM干预研究中,ComplexⅠ在M组及MR组显著增加,ComplexⅡ在所有组间无显著变化,ComplexⅣ在M组和MR组也表现出增加的趋势,但是无统计学显著差异。
5)运动联合RPM干预研究中,P-Ser473-Akt蛋白水平在M组和MR组出现同样的显著增加,PGC-1α和NRF-2蛋白水平在M组显著增加。
6)mtDNA在单纯运动干预研究没有出现显著性变化,但M组出现增加的趋势(P=-0.083),在运动联合RPM干预研究中的各组同样没有出现显著性变化,但是M组和MR组均出现增加趋势(P分别为0.08和0.095)。COXⅣ在单纯运动干预研究的M组显著增加,且和H组比较有显著差异;在运动联合RPM干预研究中,M组和MR组均显著增加。
结论:1)ROS在线粒体发生过程中发挥重要的第二信使作用,但是长期运动训练后ROS生成可能与急性运动后的变化有所不同。2周运动后安静状态下线粒体ROS生成并没有显著变化,此外,RPM单独使用或者联合运动干预也不会影响安静状态下线粒体ROS生成。
2)运动训练增加ComplexⅠ蛋白含量和活性等,增强线粒体呼吸和氧化功能。RPM抑制了脑线粒体ComplexⅠ活性及运动对ComplexⅠ活性的激活,但是在肝脏和骨骼肌组织中没有出现这一现象,提示不同组织对RPM反应的敏感程度不同。对于其它线粒体呼吸链复合物如ComplexⅡ和Ⅳ蛋白的表达,可能需要更长运动周期或者不同运动方式促使其变化。
3)耐力运动激活Akt,从而有可能激活mTOR信号通路,且RPM的使用并不能阻止运动对Akt的激活。
4)中等强度运动通过促进骨骼肌PGC-1α和NRF2蛋白表达增加促进线粒体发牛,2周后COXⅣ基因表达显著增加,mtDNA呈上升趋势,而RPM在一定程度上抑制了运动介导的线粒体发生。
二两种自行车运动对人骨骼肌线粒体发生及脂肪酸代谢相关信号基因表达的影响
方法:选取了9名无规律运动训练史的健康受试者,采用两种相同强度(60%VO_(2max))和持续时间(90min)但不同形式的运动,即持续性(Con)和间歇性(In)自行车运动,分别检测运动前(Pre)、运动后即刻(Post)及运动后3小时恢复期(3 hs Post)气体代谢、血液生化学指标及以PGC-1α为核心的一系列转录因子基因表达的变化。持续性自行车运动中,整个过程运动强度保持恒定的60%VO_(2max)的水平;间歇性自行车运动,运动强度为120%VO_(2max)持续12秒和20%VO_(2max)持续18秒轮流交替。两种运动强度相等,持续时间均为90分钟。两次运动相隔至少两周时间进行。运动前、运动中每30分钟各收集呼出气体一次分析气体代谢指标。血标本和肌肉标本分别在运动前、运动结束即刻和运动后3小时获取,用于检测血糖、血乳酸和游离脂肪酸(FFA)浓度及线粒体发生和脂肪酸代谢相关的多种信号基因的表达。
结果:1)气体代谢指标RQ、VO_2(L/min)、VO_2(ml/min.kg weight)、Vent、Vent/VO_2,及HR、RPE等,在In组和Con组均极为相似和接近。
2)血乳酸在In和Con组的Post显著升高(P＜0.05),在3 hs Post时恢复到安静水平;FFA在In和Con组的Post和3 hs Post均显著升高(P＜0.05)(在In组和Con组分别升高了2.7和3.3倍),且Post和3 hs Post的FFA浓度十分相似和接近;Glucose在In和Con组的Post(P＜0.01)和3 hs Post均显著降低(P＜0.05)。
3)Con组和In组,PGC-1αmRNA和PRCmRNA在Post均有增加的趋势(P＞0.05),但直至3 hs Post才显著升高,且3 hs Post与Post间具有显著差异。PGC-1α在Con组和In组3 hs Post分别升高了4.6倍和6.9倍;PRC在Con组和In组3 hs Post分别升高了3.0倍和3.3倍。PGC-1βmRNA在Con组和In组都没有发现显著性差异。
4)NRF-1 mRNA在Con和In组均显著下降。在Con中Post和3 hs Post时间点NRF-1 mRNA分别下降了22%(P＜0.05)和34%(P＜0.05);在In组Post和3hs Post时间点分别下降了25%(P＜0.05)和9%(P＞0.05)。NRF-2只在In组中出现显著下降,Post和3 hs Post分别下降了33%(P＜0.05)利26%(P＜0.05);在Con组有下降的趋势(Post和3 hs Post分别下降了14%和13%),但是没有达到统计学差异。与NRF-1和NRF-2关系及其密切,负责mtDNA转录和复制的调节因子:Tfam、TFBlM和TFB2M,在Con和In组运动前后均没有发生显著性变化。
5)AMPKα1 mRNA在Con和In组运动前后没有发生显著性改变,但是AMPKα2 mRNA在Con和In组运动后均显著降低(Con组和In组3 hs Post分别降低了36%和43%),且3 hs Post与Post比较,均具有显著差异(P＜0.05)。
6)PPARs家族的3个成员中PPARα和PPARβmRNA在Con和In组中均没有发生显著性变化;PPARγmRNA只在Con组的3 hs Post显著降低(下降了23%),In组没有发生显著性变化。3个成员在运动后的变化之间没有发现显著的相关关系。
7)PDK4表现出与PGC-1α及PRC十分相似的变化特点。Con组和In组Post均具有升高趋势(3.0倍和2.2倍),但无显著性差异,3 hs Post显著上升(16倍和6.7倍),且与运动后即刻比较显著差异。CPTⅠβmRNA在运动后出现下降的趋势。在Con组和In组分别下降了18%和28%(Post)及41%和21%(3 hsPost)。但是,只有Con组3 hs Post(下降41%)具有统计学显著差异。LPLmRNA在两组运动后表现出非常相似的变化趋势,Post下降(Con组和In组分别下降了9%和23%),3 hs Post稍有所升高(Con组和In组分别上升了1.06和1.14倍),但是无统计学显著差异。
8)PGC-1α和PGC-1βmRNA在Con组和In组中Post和3 hs Post的变化均具有显著的正相关关系。TFB1M和TFB2M mRNA在Con组和In组中3 hs PostmRNA的变化均具有显著正相关关系(P分别＜0.01和＜0.001),但是在Con组和In组Post的变化却没有出现显著相关关系。
结论:1)两种相同强度、相同时间,但不同形式自行车运动(持续性和间歇性)运动对机体造成相似的应激,对线粒体发生和脂肪酸代谢相关信号基因表达的影响间也无显著差异。
2)运动对PGC-1家族成员的调节有所不同。90分钟中等强度(60%VO_(2max))自行车运动后,PGC-1α、PRC mRNA在运动后3小时均显著增加,而PGC-1βmRNA没有变化。PDK4 mRNA的变化和PGC-1α及PRC十分相似。这些都提示急性运动可能通过激活重要的相关转录因子等促进线粒体发生和脂肪酸氧化等。
3)90分钟中等强度(60%VO_(2max))自行车运动后,NRF-1、NRF-2、AMPKα2、PPARγ、CPT-ⅠβmRNA等出现了不同程度的下降,这说明急性运动后某些基因可能受到抑制,或者至少这些基因的变化不是简单的运动后升高变化,可能存在先抑制后激活等变化特点,另外急性运动后机体的反应和长期运动带来的变化可能有所不同,甚至完全相反。
全文总结:1)2周中等强度和高强度运动虽然没有改变安静状态下线粒体ROS生成水平,但是显著增加了线粒体呼吸链复合物活性和蛋白表达。中等强度运动促进线粒体发生,与线粒体发生相关的信号蛋白P-Ser473-Akt、PGC-1α及NRF-2蛋白表达及COXⅣ基因表达显著增加,mtDNA基因表达也呈增加趋势。
2)气体代谢指标、血乳酸、FFA和血糖等指标变化在90分钟中等强度(60%VO_(2max))持续性和间歇性自行车运动干预下变化十分接近,且多种线粒体发生及代谢相关的信号基因变化也十分相似。
3)90分钟中等强度(60%VO_(2max))持续性和间歇性自行车运动后PGC-1α、PRC和PDK4均在运动后即刻呈增加趋势,结束后3小时显著升高;PGC-1β无显著变化;NRF-1、NRF-2、AMPKα2、PPARγ、CPT-ⅠβmRNA等出现了不同程度的下降,提示急性运动后线粒体发生和代谢相关的基因激活从而促进线粒体发生和增加脂肪酸动员和氧化供能,但是某些基因可能受到抑制,或者至少这些基因的变化不是简单的运动后升高,可能存在先抑制后激活等其它变化特点,也提示急性运动后机体的反应和长期运动带来的变化可能有所不同,甚至完全相反。
Skeletal muscle exhibits remarkable adaptive capabilities in response to a number of physiological and pathophysiological conditions.Chronic contractile activities induce mitochondrial biogenesis and increase fatty acids oxidation in skeletal muscle.These adaptations are highly specific and dependent upon the type of exercise(i.e.)resistance vs endurance)as well as its frequency,intensity and duration.A coordinated alteration in the expression of a variety of nuclear DNA and mitochondrial DNA(mtDNA)gene is needed for the adaptations.The molecular mechanism still remains unclear.One of the most important biological processes is ROS production in the exercise-induced mitochondrial biogenesis which changes the redox state of cell.Acute exercise may be a stress for the body because of the increased ROS production.The ROS induced by long term moderate exercise may play critical role in mitochondrial biogenesis.Studies suggest mTOR signal is associated with mitochondrial function and is regulated by the redox state of cell.This may be the potential mechanism links mitochondrial activity to mTOR under regulation of nutrition and other physiological and pathophysiological conditions.
The effect of exercise on mTOR signal is not clear.It is thought that endurance exercise and resistance exercise can selectively activate either AMPK/PGC-1αor Akt/mTOR signaling,respectively and the activated AMPK/PGC-1αmay inhibit Akt/mTOR signaling.However,there are some contradict findings.More delicately designed study is needed to make clear about the effects of exercise on AMPK/PGC-1αand Akt/mTOR signaling and it is worth to probe the role of AMPK/PGC-1αas well as Akt/mTOR signal pathway in mitochondrial biogenesis and metabolism.
There is a growing understanding that gene-specific transcriptional activation during and after a bout of exercise is involved,to some extent,in reestablishing homeostasis in skeletal muscle after the exercise bout,as well as contributing to the skeletal muscle adaptations that occur in response to exercise training.PGC-1αis thought to play a pivotal role in these processes.The positive effects of PGC-1αon transcription are thought to be mediated by its ability to bind to specific transcription factors recruit additional coactivators,thereby enhancing the overall efficiency of the transcriptional machinery.PGC-1αcan influence fatty acids oxidation andβ-oxidation through co- activating PPARαandγand influence uncoupling respiration by regulating UCPs transcription.NRF-1,as a strong coactivator of PGC-1α,leads to increased levels of several nuclear-encoded mitochondrial proteins,including Tfam,provokes an increase in mtDNA transcription and replication.Tfam,together with TFB1M and TFB2M,which is closely associated with NRFs,is responsible for the expression of various transcription factors coded by nuclear DNA and mtDNA.Although the entire transcriptional response to endurance exercise has not been currently demonstrated,a single bout of endurance exercise has been shown to increase mRNA expression of a growing number of genes, the majority of which are involved in mitochondrial biogenesis and fatty acids metabolism,such as NRFs,Tfam,PPARα,PDK4,LPL and CPTⅠ.
The purposes of the current study were as follows.One was to test the effects of different intensities of exercise,which included moderate intensity and high intensity,on mitochondrial biogenesis and to test the role of mTOR signal in the exercise-induced mitochondrial biogenesis.The second purpose was to test the effects of two kinds of acute cycling exercise on the expression of various transcription factors which related to mitochondrial biogenesis and fatty acids oxidation.
1 The effects of exercise and exercise combined with mTOR inhibitor on rat mitochondrial biogenesis.
Method:Following one week of adaptive feeding,24 SD rats underwent adaptive training for 3 days.After this,they were divided into different groups.The first 18 rats were divided into 3 groups which included control group(C),moderate intensity exercise group(M)and high intensity exercise group(H).The second 24 rats were divided into 4 groups which include control(C),RPM group(R),moderate intensity exercise group(M) and moderate intensity exercise combined with RPM group(MR).There are 6 rats in each group.
For the first 18 rats,following 1 week of progressed increasing intensity exercise,M and H groups were trained on the treadmill under moderate and high intensity for 1 hour every time and 5 times a week which last for 2 weeks and C group didn't do any exercise. They were killed 48 hours after the last time exercise.Mitochondria were isolated from skeletal muscle and were used for testing ROS production.The other part of skeletal muscle were saved in -80℃for testing complexⅠ,ⅡandⅣproteins level as well as mtDNA and COXⅣgene expression later.
For the second 24 rats,following 1 week of progressed increasing intensity exercise, M and MR groups were trained on the treadmill with moderate and high intensity for 1 hour every time and 5 times a week which last for 2 weeks and C and R groups didn't do any exercise.R and MR groups were injected with RPM(2mg/kg mass)for 5 times a week and the injection was carried out 1 hour before the beginning of exercise every time. All the rats were killed 48 hours after the last time exercise.Mitochondria were isolated from skeletal muscle,brain and liver which were used for testing ROS production and complexⅠactivity.The other part of skeletal muscle were saved in -80℃for testing complexⅠ,Ⅱ,Ⅳproteins level and P-Ser-473 Akt,PGC-1αand NRF-2 protein level as well as mtDNA and COXⅣgene expression.
Results:1)There was no significant change of ROS production at rest among C,M and H group in the first 18 rats and among C,R,M and MR groups in the second 24 rats (P＞0.05).
2)ComplexⅠactivity was tested only in the second 24 rats.It increased significantly in M group from mitochondria isolated from all three tissues(brain,liver and skeletal)in the second 24 rats(P＜0.05).The same change also appeared in MR group from live mitochondria.ComplexⅠactivity decreased significantly in R group from brain mitochondria and there was significant difference between M and R groups(P＜0.05).
3)ComplexⅠprotein expression increased significantly in M and H groups in the first 18 rats.ComplexⅡprotein didn't change among three groups and ComplexⅣprotein had the trend to increase in M and H group but without significance.
4)ComplexⅠprotein expression increased in M and MR groups in the second 24 rats.ComplexⅡhad no change among four groups and Complexiv had trend to increase in M and MR groups,but without significance.
5)P-Ser473-Akt protein expression increased significantly in M and MR groups and PGC-1αand NRF-2 protein expression increased significantly only in M group.
6)mtDNA expression showed trend to increase in M group(P=0.083)in the first 18 rats and in the M and MR groups(P=0.08,0.095)in the second 24 rats.COXⅣgene expression increased significantly in M group and was significantly different with H group in the first 18 rats and also increased significantly in M and MR groups in the second 24 rats.
Conclusions:1)ROS may play an important role in mitochondrial biogenesis. However,there may be difference between the effects of acute and long term exercise on ROS production.Mitochondrial ROS production at rest didn't change either after 2 weeks of exercise or exercise combined with RPM injection.
2)Exercise training increased ComplexⅠactivity in mitochondria from skeletal muscle,brain and liver as well as ComplexⅠprotein expression in skeletal muscle.RPM inhibited ComplexⅠactivity in brain tissue but not in skeletal and liver.2 weeks of exercise didn't change ComplexⅡandⅣprotein level which suggested that longer or different style of exercise might be needed to stimulate their changes.
3)Endurance training activated Akt/mTOR signaling by increasing Akt phosphorylation in a RPM independent way.
4)Moderate intensity exercise induced mitochondrial biogenesis by stimulating the protein expression of PGC-1αand NRF2.RPM could inhibit the effects and the increase in COXⅣand mtDNA gene expression induced by exercise to some extent.
2 The effects of two kinds of cycling exercise on human skeletal muscle mitochondrial biogenesis and fatty acids oxidation and the related signal gene expression.
Method:Nine healthy subjects who didn't exercise regularly for at least 6 months before the test were recruited.Two different styles of cycling exercise(continuous and intermittent)with the same intensity(60%VO_(2max))and duration time(90min)were carried out on these 9 subjects on separate day.For continuous exercise(Con),the intensity was kept at constant 60%VO_(2max)level for 90min and for the intermittent exercise(In),the intensity is consist of 120%VO_(2max)for 12sec and 20%VO_(2max)for 18sec and repeated like this for 90min.The expired gas was collected during exercise which used for analyzing the gas metabolism.Blood and muscle sample were taken before exercise(Pre),immediately after exercise(Post)and 3 hours after exercise(3hs Post) which used for testing fatty acids(FFA),lactate and glucose as well as the gene expression of various transcription factors who closely related to mitochondrial biogenesis and fatty acids can be tested.
Results:1)Metabolism indexes,such as RQ,VO_2(L/min),VO_2(ml/min.kg weight), Vent,Vent/VO_2,and HR,RPE etc.were very close to each other in In and Con groups.
2)Lactate increased significantly at Post in In and Con(P＜0.05)and returned to base level at 3 hs Post.FFA increased significantly at Post and 3 hs Post in Con and In groups(P＜0.05).Glucose decreased significantly in In and Con at Post(P＜0.01)and 3 hs Post(P＜0.05).
3)PGC-1αand PRC mRNA increased after exercise but only show significant 3 hs Post in Con and In Groups and there was significant difference between Post and 3 hs Post.PGC-1αmRNA increased 4.6 and 6.9 folds 3 hs Post in Con and In respectively and PRC increased 3.0 and 3.3 folds.There was no significant change of PGC-1βmRNA.
4)NRF-1 mRNA decreased in Con and In groups.NRF-1 mRNA decreased 22%(P＜0.05)and 34%(P＜0.05)at Post and 3 hs Post in Con group and 25%(P＜0.05)and 9%(P＞0.05)in In group respectively.NRF-2 mRNA decreased significantly only in In group which decreased 33%(P＜0.05)and 26%(P＜0.05)at Post and 3 hs Post.It showed trend to decrease but without significance(decreased 14%and 13%at Post and 3 hs Post respectively)in Con group.No significant change happened on Tfam,TFB1M and TFB2M mRNA in Con and In groups.
5)AMPKα1 didn't change but AMPKα2 decreased significantly at 3 hs Post in Con and In groups(36%and 43%in Con and In group respectively)and both were different with Post(P＜0.05)。
6)PPARαand PPARβmRNA didn't change significantly while PPARγdecreased significantly 3 hs Post in Con(23%)not In group.There is no correlation between the expression of three PPARs subunits.
7)PDK4 mRNA showed similar change with PGC-1αand PRC and increased 3.0 and 2.2 folds at Post(P＞0.05)and increased 16 and 6.7 folds 3 hs Post in Con and In groups respectively(P＜0.05).CPTⅠβmRNA decreased at Post but only show significance at 3 hs Post in Con group.LPL mRNA showed trend to decrease at Post and increase at 3 hs Post and both of them had no significance.
8)The expression of PGC-1αmRNA was positively correlated with PGC-1βin Con and In groups both at Post and 3 hs Post.The positive correlation also existed between TFB1M and TFB2M mRNA in Con and In groups at 3 hs Post(P＜0.01,＜0.001 respectively)but not at Post.
Conclusions:1)Two kinds of cycling exercise(continuous and intermittent)with same intensity(60%VO_(2max))and duration time(90min)caused similar stress and similar changes in the gene expression of transcription factors related to mitochondrial biogenesis and fatty acids oxidation.
2)The regulations of PGC-1 family members by exercise were different.90 min moderate intensity(60%VO_(2max))cycling caused significant increase in PGC-1αand PRC mRNA but no change in PGC-1βmRNA.PDK4 mRNA showed similar change with PGC-1αand PRC.These suggested that acute exercise may promote mitochondrial biogenesis and fatty acids oxidation by activating important transcription factors involved.
3)NRF-1、NRF-2、AMPKα2、PPARγand CPT-ⅠβmRNA decreased after 90 min moderate intensity(60%VO_(2max))cycling.This suggested that some genes were inhibited after acute exercise or at least were inhibited at some time points after acute exercise.It could not be excluded that they would be activated after short time inhibition. It also suggested that the change after acute exercise might be totally different with that after long term exercise.
Summary:1)2 weeks of moderate and high intensity exercise enhanced mitochondrial respiration chain complexes activity and protein expression though had no effect on ROS production at rest.Moderate exercise promoted mitochondrial biogenesis as evidenced by significantly increased Akt,PGC-1αand NRF-2 protein expression, COXⅣ,mtDNA gene expression.
2)Two kinds of cycling exercise(continuous and intermittent)with same intensity (60%VO_(2max))and duration time(90min)caused similar stress to body and similar changes in FFA,Lactate and Glucose as well as the gene expression of transcription factors related to mitochondrial biogenesis and fatty acids oxidation.
3)PGC-1α,PRC and PDK4 mRNA increased significantly after 90 min moderate intensity(60%VO_(2mxa))cycling,but PGC-1βmRNA has no change and NRF-1,NRF-2, AMPKα2,PPARγand CPT-ⅠβmRNA decreased significantly.These suggested that mitochondrial biogenesis and fatty acid mobilization and oxidation were induced by a bout of endurance exercise while some other related genes were inhibited or at least inhibited temperally.It could not be excluded that these genes would be activated after short time inhibition.The change after acute exercise might be quite different with that after long term exercise.
引文
Adhihetty,P.J.,I.Irrcher,et al.(2003)."Plasticity of skeletal muscle mitochondria in response to contractile activity." Exp Physiol 88(1):99-107.
Akimoto,T.,S.C.Pohnert,et al.(2005)."Exercise stimulates Pgc-1 alpha transcription in skeletal muscle through activation of the p38 MAPK pathway." J Biol Chem 280(20):19587-93.
Andersson,U.and R.C.Scarpulla(2001)."Pgc-l-related coactivator,a novel,seruminducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells." Mol Cell Biol 21(11):3738-49.
Ascensao,A.A.,J.F.Magalhaes,et al.(2005)."Cardiac mitochondrial respiratory function and oxidative stress:the role of exercise." Int J Sports Med 26(4):258-67.
Atherton,P.J.,J.Babraj,et al.(2005)."Selective activation of AMPK-PGC-1 alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation." FASEB J 19(7):786-8.
Attardi,G.and G.Schatz(1988)."Biogenesis of mitochondria." Annu Rev Cell Biol 4:289-333.
Baar,K.(2004)."Involvement of PPAR gamma co-activator-1,nuclear respiratory factors 1 and 2,and PPAR alpha in the adaptive response to endurance exercise."Proc Nutr Soc 63(2):269-73.
Baar,K.and K.Esser(1999)."Phosphorylation of p70(S6k)correlates with increased skeletal muscle mass following resistance exercise." Am J Physiol 276(1 Pt 1):C120-7.
Baar,K.,A.R.Wende,et al.(2002)."Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1." FASEB J 16(14):1879-86.
Barak,Y.,D.Liao,et al.(2002)."Effects ofperoxisome proliferator-activated receptor delta on placentation,adiposity,and colorectal cancer." Proc Natl Acad Sci U S A 99(1):303-8.
Barak,Y.,M.C.Nelson,et al.(1999)."PPAR gamma is required for placental,cardiac,and adipose tissue development." Mol Cell 4(4):585-95.
Barbier,O.,I.P.Torra,et al.(2002)."Pleiotropic actions ofperoxisome proliferatoractivated receptors in lipid metabolism and atherosclerosis." Arterioscler Thromb Vasc Biol 22(5):717-26.
Bejma,J.and L.L.Ji(1999)."Aging and acute exercise enhance free radical generation in rat skeletal muscle." J Appl Physiol 87(1):465-70.
Bengtsson,J.,T.Gustafsson,et al.(2001)."Mitochondrial transcription factor A and respiratory complex Ⅳ increase in response to exercise training in humans."Pflugers Arch 443(1):61-6.
Bodine,S.C.,T.N.Stitt,et al.(2001)."Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo." Nat Cell Biol 3(11):1014-9.
Bonawitz,N.D.,M.Chatenay-Lapointe,et al.(2007)."Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression." Cell Metab 5(4):265-77.
Bonen,A.,D.J.Dyck,et al.(1999)."Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36." Am J Physiol 276(4 Pt 1):E642-9.
Braissant,O.,F.Foufelle,et al.(1996)."Differential expression ofperoxisome proliferator-activated receptors(PPARs):tissue distribution of PPAR-alpha,-beta,and -gamma in the adult rat." Endocrinology 137(1):354-66.
Bustin,S.A.and T.Nolan(2004)."Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction." J Biomol Tech 15(3):155-66.
Carter,S.L.,C.Rennie,et al.(2001)."Substrate utilization during endurance exercise in men and women after endurance training." Am J Physiol Endocrinol Metab 280(6):E898-907.
Cheung,P.C.,I.P.Salt,et al.(2000)."Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding." Biochem J 346 Pt 3:659-69.
Cho,S.H.,C.H.Lee,et al.(2004)."Redox regulation of PTEN and protein tyrosine phosphatases in H(2)O(2)mediated cell signaling." FEB S Lett 560(1-3):7-13.
Cunningham,J.T.,J.T.Rodgers,et al.(2007)."mTOR controls mitochondrial oxidative function through a YY1-PGC-lalpha transcriptional complex." Nature 450(7170):736-40.
Das,S.,J.E.Dixon,et al.(2003)."Membrane-binding and activation mechanism of PTEN." Proc Natl Aead Sci U S A 100(13):7491-6.
Daussin,F.N.,J.Zoll,et al.(2008)."Training at high exercise intensity promotes qualitative adaptations of mitochondrial function in human skeletal muscle." J Appl Physiol.
Davies,K.J.,A.T.Quintanilha,et al.(1982)."Free radicals and tissue damage produced by exercise." Biochem Biophys Res Commun 107(43:1198-205.
Denyer,G.S.,G.J.Cooney,et al.(1991)."Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex." Pflugers Arch 419(2):115-20.
Desai,B.N.,B.R.Myers,et al.(2002)."FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction." Proc Natl Acad Sci U S A 99(7):4319-24.
Dressel,U.,T.L.Allen,et al.(2003)."The peroxisome proliferator-activated receptor beta/delta agonist,GW501516,regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells." Mol Endocrinol 17(12):2477-93.
Dreyer,H.C.,S.Fujita,et al.(2006)."Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle."J Physiol 576(Pt 2):613-24.
Falkenberg,M.,M.Gaspari,et al.(2002)."Mitochondrial transcription factors B1 and B2activ ate transcription of human mtDNA." Nat G enet 31(3):289-94.
Finck,B.N.and D.P.Kelly(2006)."PGC-1 coactivators:inducible regulators of energy metabolism in health and disease." J Clin Invest 116(3):615-22.
Finkel,T.and N.J.Holbrook(2000)."Oxidants,oxidative stress and the biology of ageing." Nature 408(6809):239-47.
Gagnon,J.,T.T.Kurowski,et al.(1991)."Correlations between a nuclear and a mitochondrial mRNA of cytochrome c oxidase subunits,enzymatic activity and total mRNA content,in rat tissues." Mol Cell Biochem 107(1):21-9.
Garesse,R.and C.G.Vallejo(2001)."Animal mitochondrial biogenesis and function:a regulatory cross-talk between two genomes." Gene 263(1-2):1-16.
Glass,D.J.(2003)."Molecular mechanisms modulating muscle mass." Trends Mol Med 9(8):344-50.
Gleyzer,N.,K.Vercauteren,et al.(2005)."Control of mitochondrial transcription specificity factors(TFB1M and TFB2M)by nuclear respiratory factors(NRF-1and NRF-2)and PGC-1 family coactivators." Mol Cell Biol 25(4):1354-66.
Goto,M.,S.Terada,et al.(2000)."cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats." Biochem Biophys Res Commun 274(2):350-4.
Goto,S.,H.Naito,et al.(2007)."Hormetic effects of regular exercise in aging:correlation with oxidative stress." Appl Physiol Nutr Metab 32(5):948-53.
Gredilla,R.,A.Sanz,et al.(2001)."Caloric restriction decreases mitochondrial free radical generation at complex Ⅰ and lowers oxidative damage to mitochondrial DNA in the rat heart." FASEB J 15(9):1589-91.
Hardie,D.G.(2004)."AMP-activated protein kinase:a key system mediating metabolic responses to exercise." Med Sci Sports Exerc 36(1):28-34.
Hardie,D.G.and K.Sakamoto(2006)."AMPK:a key sensor of fuel and energy status in skeletal muscle." Physiology(Bethesda)21:48-60.
Harman,D.(1956)."Aging:a theory based on free radical and radiation chemistry." J Gerontol 11(3):298-300.
Harrington,L.S.,G.M.Findlay,et al.(2005)."Restraining PI3K:mTOR signalling goes back to the membrane." Trends Biochem Sci 30(1):35-42.
Hayashi,R.,T.Ueda,et al.(2007)."Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene." Mitochondrion 7(3):195-203.
Herrero,A.and G.Barja(1997)."Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon." Mech Ageing Dev 98(2):95-111.
Higuchi,M.,L.J.Cartier,et al.(1985)."Superoxide dismutase and catalase in skeletal muscle:adaptive response to exercise." J Gerontol 40(3):281-6.
Hildebrandt,A.L.,H.Pilegaard,et al.(2003)."Differential transcriptional activation of select metabolic genes in response to variations in exercise intensity and duration." Am J Physiol Endocfinol Metab 285(5):E1021-7.
Holloszy,J.O.(1967)."Biochemical adaptations in muscle.Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle."J Biol Chem 242(9):2278-82.
Hoist,D.,S.Luquet,et al.(2003)."Nutritional regulation and role ofperoxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle."Biochim Biophys Acta 1633(1):43-50.
Hood,D.A.,R.Zak,et al.(1989)."Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome-c-oxidase subunits." Eur J Biochem 179(2):275-80.
Hoppeler,H.,P.Luthi,et al.(1973)."The ultrastructure of the normal human skeletal muscle.A morphometric analysis on untrained men,women and well-trained orienteers." Pflugers Arch 344(3):217-32.
Horowitz,J.F.,T.C.Leone,et al.(2000)."Effect of endurance training on lipid metabolism in women:a potential role for PPARalpha in the.metabolic response to training." Am J Physiol Endocrinol Metab 279(2):E348-55.
Irrcher,I.,P.J.Adhihetty,et al.(2003)."Regulation of mitochondrial biogenesis in muscle by endurance exercise." Sports Med 33(11):783-93.
Jackson,M.J.(2008)."Free radicals generated by contracting muscle:by-products of metabolism or key regulators of muscle function?" Free Radic Biol Med 44(2):132-41.
Jackson,M.J.,R.H.Edwards,et al.(1985)."Electron spin resonance studies of intact mammalian skeletal muscle." Biochim Biophys Acta 847(2):185-90.
Jackson,M.J.,S.Papa,et al.(2002)."Antioxidants,reactive oxygen and nitrogen species,gene induction and mitochondrial function." Mol Aspects Med 23(1-3):209-85.
Jeukendmp,A.E.(2003)."Modulation of carbohydrate and fat utilization by diet,exercise and environment." Biochem Soc Trans 3 l(Pt 6):1270-3.
Ji,L.L.(2002)."Exercise-induced modulation of antioxidant defense." Ann N Y Acad Sci 959:82-92.
Ji,L.L.,F.W.Stratman,et al.(1988)."Antioxidant enzyme systems in rat liver and skeletal muscle.Influences of selenium deficiency,chronic training,and acute exercise." Arch Biochem Biophys 263(1):150-60.
Jorgensen,S.B.,T.E.Jensen,et al.(2007)."Role of AMPK in skeletal muscle gene adaptation in relation to exercise." Appl Physiol Nutr Metab 32(5):904-11.
Jorgensen,S.B.,J.T.Treebak,et al.(2007)."Role of AMPKalpha2 in basal,training-,and AICAR-induced GLUT4,hexokinase Ⅱ,and mitochondrial protein expression in mouse muscle." Am J Physiol Endocrinol Metab 292(1):E331-9.
Jorgensen,S.B.,B.Viollet,et al.(2004)."Knockout of the alpha2 but not alphal 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle." J Biol Chem 279(2):1070-9.
Judge,S.,Y.M.Jang,et al.(2005)."Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart." Am J Physiol Regul Integr Comp Physiol 289(6):R1564-72.
Kahn,B.B.,T.Alquier,et al.(2005)."AMP-activated protein kinase:ancient energy gauge provides clues to modem understanding of metabolism." Cell Metab 1(1):15-25.
Kannisto,K.,A.Chibalin,et al.(2006)."Differential expression ofperoxisomal proliferator activated receptors alpha and delta in skeletal muscle in response to changes in diet and exercise." Int J Mol Med 17(1):45-52.
Kiens,B.and E.A.Richter(1998)."Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans." Am J Physiol 275(2 Pt 1):E332-7.
Kim,D.H.,D.D.Sarbassov,et al.(2002)."mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery." Cell 110(2):163-75.
Koves,T.R.,P.Li,et al.(2005)."Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency." J Biol Chem 280(39):33588-98.
Kumar,C.T.,V.K.Reddy,et al.(1992)."Dietary supplementation of vitamin E protects heart tissue from exercise-induced oxidant stress." Mol Cell Biochem 111(1-2):109-15.
Lee,S.R.,K.S.Yang,et al.(2002)."Reversible inactivation of the tumor suppressor PTEN by H2O2." J Biol Chem 277(23):20336-42.
Lee,W.J.,M.Kim,et al.(2006)."AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1." Biochem Biophys Res Commun 340(1):291-5.
Leeuwenburgh,C.,J.Hollander,et al.(1997)."Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific." Am J Physiol 272(1 Pt 2):R363-9.
Leslie,N.R.,D.Bennett,et al.(2003)."Redox regulation of PI 3-kinase signalling via inactivation of PTEN." EMBO J 22(20):5501-10.
Li,Y.,J.S.Park,et al.(2006)."Cytochrome c oxidase subunit Ⅳ is essential for assembly and respiratory function of the enzyme complex." J Bioenerg Biomembr 38(5-6):283-91.
Lin,J.,C.Handschin,et al.(2005)."Metabolic control through the PGC-1 family of transcription coactivators." Cell Metab 1(6):361-70.
Lin,J.,H.Wu,et al.(2002)."Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres." Nature 418(6899):797-801.
Lunde,I.G.,M.Ekmark,et al.(2007)."PPARdelta expression is influenced by muscle activity and induces slow muscle properties in adult rat muscles after somatic gene transfer." J Physiol 582(Pt 3):1277-87.
Mahoney,D.J.,G.Parise,et al.(2005)."Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise." FASEB J 19(11):1498-500.
Marcil,M.,K.Bourduas,et al.(2006)."Exercise training induces respiratory substratespecific decrease in Ca2+-induced permeability transition pore opening in heart mitochondria." Am J Physiol Heart Circ Physiol 290(4):H1549-57.
Marone,J.R.,M.T.Falduto,et al.(1994)."Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle." J Appl Physiol 77(4):1685-90.
McArdle,A.and M.J.Jackson(2000)."Exercise,oxidative stress and ageing." J Anat 197 Pt 4:539-41.
McCubrey,J.A.,L.S.Steelman,et al.(2006)."Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance."Adv Enzyme Regul 46:249-79.
Meirhaeghe,A.,V.Crowley,et al.(2003)."Characterization of the human,mouse and rat PGC 1 beta(peroxisome-proliferator-activated receptor-gamma co-activator 1 beta)gene in vitro and in vivo." Biochem J 373(Pt 1):155-65.
Milan,D.,J.T.Jeon,et al.(2000)."A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle." Science 288(5469):1248-51.
Mortensen,O.H.,P.Plomgaard,et al.(2007)."PGC-lbeta is downregulated by training in human skeletal muscle:no effect of training twice every second day vs.once daily on expression of the PGC-1 family." J Appl Physiol 103(5):1536-42.
Muoio,D.M.,P.S.MacLean,et al.(2002)."Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor(PPAR)alpha knock-out mice.Evidence for compensatory regulation by PPAR delta." J Biol Chem 277(29):26089-97.
Murakami,T.,Y.Shimomura,et al.(1998)."Induction of nuclear respiratory factor-1expression by an acute bout of exercise in rat muscle." Biochim Biophys Acta 1381(1):113-22.
Navarro,A.and A.Boveris(2007)."The mitochondrial energy transduction system and the aging process." Am J Physiol Cell Physiol 292(2):C670-86.
Navarro,A.,C.Gomez,et al.(2004)."Beneficial effects of moderate exercise on mice aging:survival,behavior,oxidative stress,and mitochondrial electron transfer."Am J Physiol Regul Integr Comp Physiol 286(3):R505-11.
Nemoto,S.,K.Takeda,et al.(2000)."Role for mitochondrial oxidants as regulators of cellular metabolism." Mol Cell Biol 20(19):7311-8.
Neupert,W.(1997)."Protein import into mitochondria." Annu Rev Biochem 66:863-917.
Nielsen,J.N.,K.J.Mustard,et al.(2003)."5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle." J Appl Physiol 94(2):631-41.
Norrbom,J.,C.J.Sundberg,et al.(2004)."PGC-1 alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle." J Appl Physiol 96(1):189-94.
Ojuka,E.O.(2004)."Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle." Proc Nutr Soc 63(2):275-8.
Oliver,W.R.,Jr.,J.L.Shenk,et al.(2001)."A selective peroxisome proliferatoractivated receptor delta agonist promotes reverse cholesterol transport." Proc Natl Acad Sci U S A 98(9):5306-11.
Parker,W.D.,Jr.,J.K.Parks,et al.(2008)."Complex Ⅰ deficiency in Parkinson's disease frontal cortex." Brain Res 1189:215-8.
Parkington,J.D.,A.P.Siebert,et al.(2003)."Differential activation of mTOR signaling by contractile activity in skeletal muscle." Am J Physiol Regul Integr Comp Physiol 285(5):R1086-90.
Pawlikowska,P.,B.Gajkowska,et al.(2006)."Not only insulin stimulates mitochondriogenesis in muscle cells,but mitochondria are also essential for insulin-mediated myogenesis." Cell Prolif 39(2):127-45.
Peng,T.,T.R.Golub,et al.(2002)."The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation." Mol Cell Biol 22(15):5575-84.
Piantadosi,C.A.and H.B.Suliman(2006)."Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1." J Biol Chem 281(1):324-33.
Pilegaard,H.and P.D.Neufer(2004)."Transcriptional regulation ofpymvate dehydrogenase kinase 4 in skeletal muscle during and after exercise." Proc Nutr Soc 63(2):221-6.
Pilegaard,H.,G.A.Ordway,et al.(2000)."Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise." Am J Physiol Endocrinol Metab 279(4):E806-14.
Pilegaard,H.,B.Saltin,et al.(2003)."Exercise induces transient transcriptional activation of the PGC-1 alpha gene in human skeletal muscle." J Physiol 546(Pt 3):851-8.
Puigserver,P.,Z.Wu,et al.(1998)."A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis." Cell 92(6):829-39.
Rantanen,A.,M.Gaspari,et al.(2003)."Characterization of the mouse genes for mitochondrial transcription factors B1 and B2." Mamm Genome 14(1):1-6.
Reid,M.B.,D.S.Stokic,et al.(1994)."N-acetylcysteine inhibits muscle fatigue in humans." J Clin Invest 94(6):2468-74.
Reynolds,T.H.t.,S.C.Bodine,et al.(2002)."Control of Ser2448 phosphorylation in the mammalian target ofrapamycin by insulin and skeletal muscle load." J Biol Chem 277(20):17657-62.
Reynolds,T.H.t.,P.Reid,et al.(2004)."Effects of aerobic exercise training on the protein kinase B(PKB)/mammalian target of rapamycin(mTOR)signaling pathway in aged skeletal muscle." Exp Gerontol 39(3):379-85.
Reznick,R.M.and G.I.Shulman(2006)."The role of AMP-activated protein kinase in mitochondrial biogenesis." J Physiol 574(Pt 1):33-9.
Rossignol,R.,B.Faustin,et al.(2003)."Mitochondrial threshold effects." Biochem J 370(Pt 3):751-62.
Rossignol,R.,T.Letellier,et al.(2000)."Tissue variation in the control of oxidative phosphorylation:implication for mitochondrial diseases." Biochem J 347 Pt 1:45-53.
Russell,A.P.,J.Feilchenfeldt,et al.(2003)."Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptorgamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle." Diabetes 52(12):2874-81.
Russell,A.P.,M.K.Hesselink,et al.(2005)."Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise." FASEB J 19(8):986-8.
Sadana,P.,Y.Zhang,et al.(2007)."Regulation of carnitine palmitoyltransferase I(CPT-Ialpha)gene expression by the peroxisome proliferator activated receptor gamma coactivator(PGC-1)isoforms." Mol Cell Endocrinol 267(1-2):6-16.
Samelman,T.R.,L.J.Shiry,et al.(2000)."Endurance training increases the expression of mitochondrial and nuclear encoded cytochrome c oxidase subunits and heat shock proteins in rat skeletal muscle." Eur J Appl Physiol 83(1):22-7.
Sarbassov,D.D.,S.M.Ali,et al.(2005)."Growing roles for the mTOR pathway." Curr Opin Cell Biol 17(6):596-603.
Scarpulla,R.C.(2002)."Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian ceils." Gene 286(1):81-9.
Schieke,S.M.and T.Finkel(2006)."Mitochondrial signaling,TOR,and life span." Biol Chem 387(10-11):1357-61.
Schieke,S.M.,D.Phillips,et al.(2006)."The mammalian target of rapamycin(mTOR)pathway regulates mitochondrial oxygen consumption and oxidative capacity." J Biol Chem 281(37):27643-52.
Seip,R.L.,T.J.Angelopoulos,et al.(1995)."Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue." Am J Physiol 268(2 Pt 1):E229-36.
Shi,Y.,M.Hon,et al.(2002)."The peroxisome proliferator-activated receptor delta,an integrator of transcriptional repression and nuclear receptor signaling." Proc Natl Acad Sci USA 99(5):2613-8.
Silveira,L.R.,H.Pilegaard,et al.(2006)."The contraction induced increase in gene expression of peroxisome proliferator-activated receptor(PPAR)-gamma coactivator 1 alpha(PGC-lalpha),mitochondrial uncoupling protein 3(UCP3)and hexokinase Ⅱ(HKⅡ)in primary rat skeletal muscle cells is dependent on reactive oxygen species." Biochim Biophys Acta 1763(9):969-76.
Siu,P.M.,D.A.Donley,et al.(2004)."Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training." J Appl Physiol 97(1):277-85.
Sriwijitkamol,A.,D.K.Coletta,et al.(2007)."Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes:a time-course and dose-response study." Diabetes 56(3):836-48.
Starnes,J.W.,B.D.Barnes,et al.(2007)."Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction." J Appl Physiol 102(5):1793-8.
Steelman,L.S.,F.E.Bertrand,et al.(2004)."The complexity of PTEN:mutation,marker and potential target for therapeutic intervention." Expert Opin Ther Targets 8(6):537-50.
Suliman,H.B.,K.E.Welty-Wolf,et al.(2004)."Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis." Cardiovasc Res 64(2):279-88.
Supinski,G.(1998)."Free radical induced respiratory muscle dysfunction." Mol Cell.Biochem 179(1-2):99-110.
Terada,S.,M.Goto,et al.(2002)."Effects of low-intensity prolonged exercise on PGC-1mRNA expression in rat epitrochlearis muscle." Biochem Biophys Res Commun 296(2):350-4.
Timmons,J.A.,J.Norrbom,et al.(2006)."Expression profiling following local muscle inactivity in humans provides new perspective on diabetes-related genes."Genomics 87(1):165-72.
Tunstall,R.J.,K.A.Mehan,et al.(2002)."Exercise training increases lipid metabolism gene expression in human skeletal muscle." Am J Physiol Endocrinol Metab 283(1):E66-72.
Turrens,J.F.(2003)."Mitochondrial formation of reactive oxygen species." J Physiol 552(Pt 2):335-44.
Vasilaki,A.,A.Mansouri,et al.(2006)."Free radical generation by skeletal muscle of adult and old mice:effect of contractile activity." Aging Cell 5(2):109-17.
Vavvas,D.,A.Apazidis,et al.(1997)."Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle." J Biol Chem 272(20):13255-61.
Vazquez,F.,S.Ramaswamy,et al.(2000)."Phosphorylation of the PTEN tail regulates protein stability and function." Mol Cell Biol 20(14):5010-8.
Venditti,P.,A.Bari,et al.(2007)."Role of mitochondria in exercise-induced oxidative stress in skeletal muscle from hyperthyroid rats." Arch Biochem Biophys 463(1):12-8.
Venditti,P.,P.Masullo,et al.(1999)."Effect of training on H(2)O(2)release by mitochondria from rat skeletal muscle." Arch Biochem Biophys 372(2):315-20.
Venditti,P.,P.Masullo,et al.(2001)."Hemoproteins affect H(2)O(2)removal from rat tissues." Int J Biochem Cell Biol 33(3):293-301.
Virbasius,J.V.and R.C.Scarpulla(1994)."Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors:a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis."Proc Natl Acad Sci U S A 91(4):1309-13.
Watt,M.J.,R.J.Southgate,et al.(2004)."Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor(PPAR)alpha and delta and PPAR coactivator lalpha in human skeletal muscle,but not lipid regulatory genes." J Mol Endocrinol 33(2):533-44.
White,R.J.(2004)."A "radical" idea comes of age:mitochondrial oxidant signaling in health and disease." J Mol Cell Cardiol 37(6):1115-7.
Williams,R.S.,M.Garcia-Moll,et al.(1987)."Adaptation of skeletal muscle to increased contractile activity.Expression nuclear genes encoding mitochondrial proteins." J Biol Chem 262(6):2764-7.
Williamson,D.L.,N.Kubica;et al.(2006)."Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target ofrapamycin(mTOR)signalling to regulatory mechanisms of mRNA translation in mouse muscle." J Physiol 573(Pt 2):497-510.
Winder,W.W.,E.B.Taylor,et al.(2006)."Role of AMP-activated protein kinase in the molecular adaptation to endurance exercise." Med Sci Sports Exerc 38(11):1945-9.
Wu,P.,K.Inskeep,et al.(1999)."Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes." Diabetes 48(8):1593-9.
Wu,P.,J.Sato,et al.(1998)."Starvation and diabetes increase the amount ofpyruvate dehydrogenase kinase isoenzyme 4 in rat heart." Biochem J 329(Pt 1):197-201.
Wullschleger,S.,R.Loewith,et al.(2006)."TOR signaling in growth and metabolism."Cell 124(3):471-84.
丁树哲(2001).“有氧运动训练后大鼠横纹肌线粒体DNA含量观察.”中国运动医堂杂志20(4):3.
丁树哲(2002)。”有氧运动对线粒体质子跨膜转运及核糖核苷二磷酸还原酶的影响.”中国运动医学杂志21(3):244-247.
Adhihetty,P.J.,I.Irrcher,et al.(2003)."Plasticity of skeletal muscle mitochondria in response to contractile activity." Exp Physiol 88(1):99-107.
Akimoto,T.,S.C.Pohnert,et al.(2005)."Exercise stimulates Pgc-lalpha transcription in skeletal muscle through activation of the p38 MAPK pathway." J Biol Chem 280(20):19587-93.
Ascensao,A.A.,J.F.Magalhaes,et al.(2005)."Cardiac mitochondrial respiratory function and oxidative stress:the role of exercise." Int J Sports Med 26(4):258-67.
Atherton,P.J.,J.Babraj,et al.(2005)."Selective activation of AMPK-PGC-lalpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation." FASEB J 19(7):786-8.
Baar,K.and K.Esser(1999)."Phosphorylation ofp70(S6k)correlates with increased skeletal muscle mass following resistance exercise." Am J Physio1276(1 Pt 1):C120-7.
Baar,K.,A.R.Wende,et al.(2002)."Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1." FASEB J 16(14):1879-86.
Bejma,J.and L.L.Ji(1999)."Aging and acute exercise enhance free radical generation in rat skeletal muscle." J Appl Physiol 87(1):465-70.
Bengtsson,J.,T.Gustafsson,et al.(2001)."Mitochondrial transcription factor A and respiratory complex Ⅳ increase in response to exercise training in humans."Pflugers Arch 443(1):61-6.
Bodine,S.C.,T.N.Stitt,et al.(2001)."Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo." Nat Cell Biol 3(11):1014-9.
Bonawitz,N.D.,M.Chatenay-Lapointe,et al.(2007)."Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression." Cell Metab 5(4):265-77.
Cho,S.H.,C.H.Lee,et al.(2004)."Redox regulation of PTEN and protein tyrosine phosphatases in H(2)O(2)mediated cell signaling." FEBS Lett 560(1-3):7-13.
Cunningham,J.T.,J.T.Rodgers,et al.(2007).,mTOR controls mitochondrial oxidative function through a YY1-PGC-lalpha transcriptional complex." Nature 450(7170):736-40.
Das,S.,J.E.Dixon,et al.(2003)."Membrane-binding and activation mechanism of PTEN." Proc Natl Acad Sci U S A 100(13):7491-6.
Daussin,F.N.,J.Zoll,et al.(2008)."Training at high exercise intensity promotes qualitative adaptations of mitochondrial function in human skeletal muscle." J Appl Physiol.
Davies,K.J.,A.T.Quintanilha,et al.(1982)."Free radicals and tissue damage produced by exercise." Biochem Biophys Res Commun 107(4):1198-205.
Desai,B.N.,B.R.Myers,et al.(2002)."FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction." Proc Natl Acad Sci U S A 99(7):4319-24.
Dreyer,H.C.,S.Fujita,et al.(2006)."Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle."J Physiol 576(Pt 2):613-24.
Gagnon,J.,T.T.Kurowski,et al.(1991)."Correlations between a nuclear and a mitochondrial mRNA of cytochrome c oxidase subunits,enzymatic activity and total mRNA content,in rat tissues." Mol Cell Biochem 107(1):21-9.
Garesse,R.and C.G.Vallejo(2001)."Animal mitochondrial biogenesis and function:a regulatory cross-talk between two genomes." Gene 263(1-2):1-16.
Goto,M.,S.Terada,et al.(2000)."cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats." Biochem Biophys Res Commun 274(2):350-4.
Goto,S.,H.Naito,et al.(2007)."Hormetic effects of regular exercise in aging:correlation with oxidative stress." Appl Physiol Nutr Metab 32(5):948-53.
Gredilla,R.,A.Sanz,et al.(2001)."Caloric restriction decreases mitochondrial free radical generation at complex Ⅰ and lowers oxidative damage to mitochondrial DNA in the rat heart." FASEB J 15(9):1589-91.
Harrington,L.S.,G.M.Findlay,et al.(2005)."Restraining PI3K:mTOR signalling goes.back to the membrane." Trends Biochem Sci 30(1):35-42.
Herrero,A.and G.Barja(1997)."Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon." Mech Ageing Dev 98(2):95-111.
Higuchi,M.,L.J.Cartier,et al.(1985)."Superoxide dismutase and catalase in skeletal muscle:adaptive response to exercise." J Gerontol 40(3):281-6.
Holloszy,J.O.(1967)."Biochemical adaptations in muscle.Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle."J Biol Chem 242(9):2278-82.
Hood,D.A.and A.Saleem(2007)."Exercise-induced mitochondrial biogenesis in skeletal muscle." Nutr Metab Cardiovasc Dis 17(5):332-7.
Hood,D.A.,R.Zak,et al.(1989)."Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome-coxidase subunits." Eur J Biochem 179(2):275-80.
Hoppeler,H.,P.Luthi,et al.(1973)."The ultrastructure of the normal human skeletal muscle.A morphometric analysis on untrained men,women and well-trained orienteers." Pflugers Arch 344(3):217-32.
Irrcher,I.,P.J.Adhihetty,et al.(2003)."Regulation ofmitochondrial biogenesis in muscle by endurance exercise." Sports Med 33(11):783-93.
Jackson,M.J.(2008)."Free radicals generated by contracting muscle:by-products of metabolism or key regulators of muscle function?" Free Radic Biol Med 44(2):132-41.
Jackson,M.J.,R.H.Edwards,et al.(1985)."Electron spin resonance studies of intact mammalian skeletal muscle." Biochim Biophys Acta 847(2):185-90.
Ji,L.L.,F.W.Stratman,et al.(1988)."Antioxidant enzyme systems in rat liver and skeletal muscle.Influences of selenium deficiency,chronic training,and acute exercise." Arch Biochem Biophys 263(1):150-60.
Judge,S.,Y.M.Jang,et al.(2005)."Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart." Am J Physiol Regul Integr Comp Physiol 289(6):R1564-72.
Kumar,C.T.,V.K.Reddy,et al.(1992)."Dietary supplementation of vitamin E protects heart tissue from exercise-induced oxidant stress." Mol Cell Biochem 111(1-2):109-15.
Lee,S.R.,K.S.Yang,et al.(2002)."Reversible inactivation of the tumor suppressor PTEN by H2O2." J Biol Chem 277(23):20336-42.
Leeuwenburgh,C.,J.Hollander,et al.(1997)."Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific." Am J Physiol 272(1 Pt 2):R363-9.
Leslie,N.R.,D.Bennett,et al.(2003)."Redox regulation of PI 3-kinase signalling via inactivation ofPTEN." EMBO J 22(20):5501-10.
Marcil,M.,K.Bourduas,et al.(2006)."Exercise training induces respiratory substratespecific decrease in Ca2+-induced permeability transition pore opening in heart mitochondfia." Am J Physiol Heart Circ Physiol 290(4):H1549-57.
Marone,J.R.,M.T.Falduto,et al.(1994)."Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle." J Appl Physiol 77(4):1685-90.
McArdle,A.and M.J.Jackson(2000)."Exercise,oxidative stress and ageing." J Anat 197 Pt 4:539-41.
McCubrey,J.A.,L.S.Steelman,et al.(2006)."Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance."Adv Enzyme Regul 46:249-79.
Navarro,A.,C.Gomez,et al.(2004)."Beneficial effects of moderate exercise on mice aging:survival,behavior,oxidative stress,and mitochondrial electron transfer."Am J Physiol Regul Integr Comp Physiol 286(3):R505-11.
Parker,W.D.,Jr.,J.K.Parks,et al.(2008)."Complex Ⅰ deficiency in Parkinson's disease frontal cortex." Brain Res 1189:215-8.
Parkington,J.D.,A.P.Siebert,et al.(2003)."Differential activation ofmTOR signaling by contractile activity in skeletal muscle." Am J Physiol Regul Integr Comp Physiol 285(5):R1086-90.
Pawlikowska,P.,B.Gajkowska,et al.(2006)."Not only insulin stimulates mitochondriogenesis in muscle cells,but mitochondria are also essential for insulin-mediated myogenesis." Cell Prolif 39(2):127-45.
Peng,T.,T.R.Golub,et al.(2002)."The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation." Mol Cell Biol 22(15):5575-84.
Piantadosi,C.A.and H.B.Suliman(2006)."Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1." J Biol Chem 281(1):324-33.
Reid,M.B.,D.S.Stokic,et al.(1994)."N-acetylcysteine inhibits muscle fatigue in humans." J Clin Invest 94(6):2468-74.
Reynolds,T.H.t.,S.C.Bodine,et al.(2002)."Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load." J Biol Chem 277(20):17657-62.
Reynolds,T.H.t.,P.Reid,et al.(2004)."Effects of aerobic exercise training on the protein kinase B(PKB)/mammalian target ofrapamycin(mTOR)signaling pathway in aged skeletal muscle." Exp Gerontol 39(3):379-85.
Rossignol,R.,B.Faustin,et al.(2003)."Mitochondrial threshold effects." Biochem J 370(Pt 3):751-62.
Rossignol,R.,T.Letellier,et al.(2000)."Tissue variation in the control of oxidative phosphorylation:implication for mitochondrial diseases." Biochem J 347 Pt 1:45-53.
Samelman,T.R.,L.J.Shiry,et al.(2000)."Endurance training increases the expression of mitochondrial and nuclear encoded cytochrome c oxidase subunits and heat shock proteins in rat skeletal muscle." Eur J Appl Physiol 83(1):22-7.
Sarbassov,D.D.,S.M.Ali,et al.(2005)."Growing roles for the mTOR pathway." Curr Opin Cell Biol 17(6):596-603.
Scarpulla,R.C.(2002)."Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells." Gene 286(1):81-9.
Schieke,S.M.and T.Finkel(2006)."Mitochondrial signaling,TOR,and life span." Biol Chem 387(10-11):1357-61.
Schieke,S.M.,D.Phillips,et al.(2006)."The mammalian target ofrapamycin(mTOR)pathway regulates mitochondrial oxygen consumption and oxidative capacity." J Biol Chem 281(37):27643-52.
Silveira,L.R.,H.Pilegaard,et al.(2006)."The contraction induced increase in gene expression ofperoxisome proliferator-activated receptor(PPAR)-gamma coactivator lalpha(PGC-lalpha),mitochondrial uncoupling protein 3(UCP3)and hexokinase Ⅱ(HKⅡ)in primary rat skeletal muscle cells is dependent on reactive oxygen species." Biochim Biophys Acta 1763(9):969-76.
Starnes,J.W.,B.D.Barnes,et al.(2007)."Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction." J Appl Physiol 102(5):1793-8.
Steelman,L.S.,F.E.Bertrand,et al.(2004)."The complexity of PTEN:mutation,marker and potential target for therapeutic intervention." Expert Opin Ther Targets 8(6):537-50.
Suliman,H.B.,K.E.Welty-Wolf,et al.(2004)."Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis." Cardiovasc Res 64(2):279-88.
Terada,S.,M.Goto,et al.(2002)."Effects of low-intensity prolonged exercise on PGC-1mRNA expression in rat epitrochlearis muscle." Biochem Biophys Res Commun 296(2):350-4.
Turrens,J.F.(2003)."Mitochondrial formation of reactive oxygen species." J Physiol 552(Pt 2):335-44.
Vasilaki,A.,A.Mansouri,et al.(2006)."Free radical generation by skeletal muscle of adult and old mice:effect of contractile activity." Aging Cell 5(2):109-17.
Vazquez,F.,S.Ramaswamy,et al.(2000)."Phosphorylation of the PTEN tail regulates protein stability and function." Mol Cell Biol 20(14):5010-8.
Venditti,P.,A.Bari,et al.(2007)."Role ofmitochondria in exercise-induced oxidative stress in skeletal muscle from hyperthyroid rats." Arch Biochem Biophys 463(1):12-8.
Venditti,P.,P.Masullo,et al.(1999)."Effect of training on H(2)O(2)release by mitochondria from rat skeletal muscle." Arch Biochem Biophys 372(2):315-20.
Venditti,P.,P.Masullo,et al.(2001)."Hemoproteins affect H(2)O(2)removal from rat tissues." Int J Biochem Cell Biol 33(3):293-301.
White,R.J.(2004)."A "radical" idea comes of age:mitochondrial oxidant signaling in health and disease." J Mol Cell Cardiol 37(6):1115-7.
Williams,R.S.,M.Garcia-Moll,et al.(1987)."Adaptation of skeletal muscle to increased contractile activity.Expression nuclear genes encoding mitochondrial proteins." J Biol Chem 262(6):2764-7.
Williamson,D.L.,N.Kubica,et al.(2006)."Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin(mTOR)signalling to regulatory mechanisms of mRNA translation in mouse muscle." J Physiol 573(Pt 2):497-510.
Wullschleger,S.,R.Loewith,et al.(2006)."TOR signaling in growth and metabolism."Cell 124(3):471-84.
丁树哲(2001).“有氧运动训练后大鼠横纹肌线粒体DNA含量观察.”中国运动医学杂志20(4):3.
丁树哲(2002),“有氧运动对线粒体质子跨膜转运及核糖核苷二磷酸还原酶的影响.”中国运动医学杂志21(3):244—247.
Adhihetty,P.J.,I.Irrcher,et al.(2003)."Plasticity of skeletal muscle mitochondria in response to contractile activity." Exp Physiol 88(1):99-107.
Akimoto,T.,S.C.Pohnert,et al.(2005)."Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway." J Biol Chem 280(20):19587-93.
Andersson,U.and R.C.Scarpulla(2001)."Pgc-1-related coactivator,a novel,seruminducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells." Mol Cell Biol 21(11):3738-49.
Atherton,P.J.,J.Babraj,et al.(2005)."Selective activation of AMPK-PGC-1 alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation." FASEB J 19(7):786-8.
Baar,K.(2004)."Involvement of PPAR gamma co-activator-1,nuclear respiratory factors 1 and 2,and PPAR alpha in the adaptive response to endurance exercise."Proc Nutr Soc 63(2):269-73.
Baar,K.,A.R.Wende,et al.(2002)."Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1." FASEB J 16(14):1879-86.
Bahr,R.,A.T.Hostmark,et al.(1991)."Effect of exercise on recovery changes in plasma levels of FFA,glycerol,glucose and catecholamines." Acta Physiol Scand 143(1):105-15.
Barak,Y.,D.Liao,et al.(2002)."Effects of peroxisome proliferator-activated receptor delta on placentation,adiposity,and colorectal cancer." Proc Natl Acad Sci U S A 99(1):303-8.
Barak,Y.,M.C.Nelson,et al.(1999)."PPAR gamma is required for placental,cardiac,and adipose tissue development." Mol Cell 4(4):585-95.
Barbier,O.,I.P.Torra,et al.(2002)."Pleiotropic actions of peroxisome proliferatoractivated receptors in lipid metabolism and atherosclerosis." Arterioscler Thromb Vasc Biol 22(5):717-26.
Bengtsson,J.,T.Gustafsson,et al.(2001)."Mitochondrial transcription factor A and respiratory complex Ⅳ increase in response to exercise training in humans."Pflugers Arch 443(1):61-6.
Bickel,C.S.,J.Slade,et al.(2005)."Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise." J Appl Physiol 98(2):482-8.
Bonen,A.,D.J.Dyck,et al.(1999)."Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36." Am J Physiol 276(4 Pt 1):E642-9.
Braissant,O.,F.Foufelle,et al.(1996)."Differential expression of peroxisome proliferator-activated receptors(PPARs):tissue distribution of PPAR-alpha,-beta,and -gamma in the adult rat." Endocrinology 137(1):354-66.
Bustin,S.A.and T.Nolan(2004)."Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction." J Biomol Tech 15(3):155-66.
Carter,S.L.,C.Rennie,et al.(2001)."Substrate utilization during endurance exercise in men and women after endurance training." Am J Physiol Endocrinol Metab 280(6):E898-907.
Cheung,P.C.,I.P.Salt,et al.(2000)."Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding." Biochem J 346 Pt 3:659-69.
Denyer,G.S.,G.J.Cooney,et al.(1991)."Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex." Pflugers Arch 419(2):115-20.
Dressel,U.,T.L.Allen,et al.(2003)."The peroxisome proliferator-activated receptor beta/delta agonist,GW501516,regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells." Mol Endocrinol 17(12):2477-93.
Falkenberg,M.,M.Gaspari,et al.(2002)."Mitochondrial transcription factors B1 and B2activate transcription of human mtDNA." Nat Genet 31(3):289-94.
Finck,B.N.and D.P.Kelly(2006)."PGC-1 coactivators:inducible regulators of energy metabolism in health and disease." J Clin Invest 116(3):615-22.
Frosig,C.,S.B.Jorgensen,et al.(2004)."5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle."Am J Physiol Endocrinol Metab 286(3):E411-7.
Gaudet-Savard,T.,A.Ferland,et al.(2007)."Safety and magnitude of changes in blood glucose levels following exercise performed in the fasted and the postprandial state in men with type 2 diabetes." Eur J Cardiovasc Prey Rehabil 14(6):831-6.
Glass,D.J.(2003)."Molecular mechanisms modulating muscle mass." Trends Mol Med 9(8):344-50.
Gleyzer,N.,K.Vercauteren,et al.(2005)."Control of mitochondrial transcription specificity factors(TFB1M and TFB2M)by nuclear respiratory factors(NRF-1and NRF-2)and PGC-1 family coactivators." Mol Cell Biol 25(4):1354-66.
Gordon,J.W.,A.A.Rungi,et al.(2001)."Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle." J Appl Physiol 90(1):389-96.
Goto,M.,S.Terada,et al.(2000)."cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats." Biochem Biophys Res Commun 274(2):350-4.
Green,H.J.,D.J.Barr,et al.(2004)."Malleability of human skeletal muscle Na(+)-K(+)-ATPase pump with short-term training." J.Appl Physiol 97(1):143-8.
Hardie,D.G.(2004)."AMP-activated protein kinase:a key system mediating metabolic responses to exercise." Med Sci Sports Exerc 36(1):28-34.
Hardie,D.G.and K.Sakamoto(2006)."AMPK:a key sensor of fuel and energy status in skeletal muscle." Physiology(Bethesda)21:48-60.
Hayashi,R.,T.Ueda,et al.(2007)."Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene." Mitochondrion 7(3):195-203.
Hildebrandt,A.L.,H.Pilegaard,et al.(2003)."Differential transcriptional activation of select metabolic genes in response to variations in exercise intensity and duration." Am J Physiol Endocrinol Metab 285(5):E1021-7.
Holst,D.,S.Luquet,et al.(2003)."Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle."Biochim Biophys Acta 1633(1):43-50.
Hood,D.A.,M.Takahashi,et al.(2000)."Assembly of the cellular powerhouse:current issues in muscle mitochondrial biogenesis." Exerc Sport Sci Rev 28(2):68-73.
Horowitz,J.F.,T.C.Leone,et al.(2000)."Effect of endurance training on lipid metabolism in women:a potential role for PPARalpha in the metabolic response to training." Am J Physiol Endocrinol Metab 279(2):E348-55.
Jeukendrup,A.E.(2003)."Modulation of carbohydrate and fat utilization by diet,exercise and environment." Biochem Soc Trans 31(Pt 6):1270-3.
Ji,L.L.(2002)."Exercise-induced modulation of antioxidant defense." Ann N Y Acad Sci 959:82-92.
Jorgensen,S.B.,T.E.Jensen,et al.(2007)."Role of AMPK in skeletal muscle gene adaptation in relation to exercise." Appl Physiol Nutr Metab 32(5):904-11.
Jorgensen,S.B.,J.T.Treebak,et al.(2007)."Role of AMPKalpha2 in basal,training-,and AICAR-induced GLUT4,hexokinase Ⅱ,and mitochondrial protein expression in mouse muscle." Am J Physiol Endocrinol Metab 292(1):E331-9.
Jorgensen,S.B.,B.Viollet,et al.(2004)."Knockout of the alpha2 but not alphal 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle." J Biol Chem 279(2):1070-9.
Kahn,B.B.,T.Alquier,et al.(2005)."AMP-activated protein kinase:ancient energy gauge provides clues to modern understanding of metabolism." Cell Metab 1(1):15-25.
Kannisto,K.,A.Chibalin,et al.(2006)."Differential expression of peroxisomal proliferator activated receptors alpha and delta in skeletal muscle in response to changes in diet and exercise." Int J Mol Med 17(1):45-52.
Kiens,B.and E.A.Richter(1998)."Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans." Am J Physiol 275(2 Pt 1):E332-7.
Koves,T.R.,P.Li,et al.(2005)."Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency." J Biol Chem 280(39):33588-98.
Lee,W.J.,M.Kim,et al.(2006)."AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1." Biochem Biophys Res Commun 340(1):291-5.
Lin,J.,C.Handschin,et al.(2005)."Metabolic control through the PGC-1 family of transcription coactivators." Cell Metab 1(6):361-70.
Lin,J.,H.Wu,et al.(2002)."Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres." Nature 418(6899):797-801.
Lunde,I.G.,M.Ekmark,et al.(2007)."PPARdelta expression is influenced by muscle activity and induces slow muscle properties in adult rat muscles after somatic gene transfer." J Physiol 582(Pt 3):1277-87.
Mahoney,D.J.,G.Parise,et al.(2005)."Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise." FASEB J 19(11):1498-500.
Marion-Latard,F.,F.Crampes,et al.(2003)."Post-exercise increase of lipid oxidation after a moderate exercise bout in untrained healthy obese men." Horm Metab Res 35(2):97-103.
MAUD,P.C.F.,Ed.(1995).Physiological Assessment of Human Fitness.Champaign,IL:Human Kinetics,.
Meirhaeghe,A.,V.Crowley,et al.(2003)."Characterization of the human,mouse and rat PGC1 beta(peroxisome-proliferator-activated receptor-gamma co-activator 1 beta)gene in vitro and in vivo." Biochem J 373(Pt 1):155-65.
Milan,D.,J.T.Jeon,et al.(2000)."A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle." Science 288(5469):1248-51.
Mortensen,O.H.,P.Plomgaard,et al.(2007)."PGC-lbeta is downregulated by training in human skeletal muscle:no effect of training twice every second day vs.once daily on expression of the PGC-1 family." J Appl Physiol 103(5):1536-42.
Muoio,D.M.,P.S.MacLean,et al.(2002)."Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor(PPAR)alpha knock-out mice.Evidence for compensatory regulation by PPAR delta." J Biol Chem 277(29):26089-97.
Murakami,T.,Y.Shimomura,et al.(1998)."Induction of nuclear respiratory factor-1expression by an acute bout of exercise in rat muscle." Biochim Biophys Acta 1381(1):113-22.
Nielsen,J.N.,K.J.Mustard,et al.(2003)."5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle." J Appl Physiol 94(2):631-41.
Norrbom,J.,C.J.Sundberg,et al.(2004)."PGC-1 alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle." J Appl Physiol 96(1):189-94.
Ojuka,E.O.(2004)."Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle." Proc Nutr Soc 63(2):275-8.
Oliver,W.R.,Jr.,J.L.Shenk,et al.(2001)."A selective peroxisome proliferatoractivated receptor delta agonist promotes reverse cholesterol transport." Proc Natl Acad Sci U S A 98(9):5306-11.
Pilegaard,H.and P.D.Neufer(2004)."Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise." Proc Nutr Soc 63(2):221-6.
Pilegaard,H.,G.A.Ordway,et al.(2000)."Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise." Am J Physiol Endocrinol Metab 279(4):E806-14.
Pilegaard,H.,B.Saltin,et al.(2003)."Exercise induces transient transcriptional activation of the PGC-1 alpha gene in human skeletal muscle." J Physiol 546(Pt 3):851-8.
Puigserver,P.,Z.Wu,et al.(1998)."A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis." Cell 92(6):829-39.
Rantanen,A.,M.Gaspari,et al.(2003)."Characterization of the mouse genes for mitochondrial transcription factors B1 and B2." Mamm Genome 14(1):1-6.
Rantzau,C.,M.Christopher,et al.(2008)."Contrasting effects of exercise,AICAR,and increased fatty acid supply on in vivo and skeletal muscle glucose metabolism." J Appl Physiol 104(2):363-70.
Reznick,R.M.and G.I.Shulman(2006)."The role of AMP-activated protein kinase in mitochondrial biogenesis." J Physiol 574(Pt 1):33-9.
Russell,A.P.,J.Feilchenfeldt,et al.(2003)."Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor- gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle." Diabetes 52(12):2874-81.
Russell,A.P.,M.K.Hesselink,et al.(2005)."Regulation of metabolic transcriptional coactivators and transcription factors with acute exercise." FASEB J 19(8):986-8.
Sadana,P.,Y.Zhang,et al.(2007)."Regulation of carnitine palmitoyltransferase Ⅰ(CPTIalpha)gene expression by the peroxisome proliferator activated receptor gamma coactivator(PGC-1)isoforms." Mol Cell Endocrinol 267(1-2):6-16.
Sari,R.,M.K.Balci,et al.(2007)."Acute effect of exercise on plasma leptin level and insulin resistance in obese women with stable caloric intake." Endocr Res 32(1-2):9-17.
Scarpulla,R.C.(2002)."Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells." Gene 286(1):81-9.
Seip,R.L.,T.J.Angelopoulos,et al.(1995)."Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue." Am J Physiol 268(2 Pt 1):E229-36.
Shi,Y.,M.Hon,et al.(2002)."The peroxisome proliferator-activated receptor delta,an integrator of transcriptional repression and nuclear receptor signaling." Proc Natl Acad Sci U S A 99(5):2613-8.
Siu,P.M.,D.A.Donley,et al.(2004)."Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training." J Appl Physiol 97(1):277-85.
Sriwijitkamol,A.,D.K.Coletta,et al.(2007)."Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes:a time-course and dose-response study." Diabetes 56(3):836-48.
Terada,S.,M.Goto,et al.(2002)."Effects of low-intensity prolonged exercise on PGC-1mRNA expression in rat epitrochlearis muscle." Biochem Biophgs Res Commun 296(2):350-4.
Timmons,J.A.,J.Norrbom,et al.(2006)."Expression profiling following local muscle inactivity in humans provides new perspective on diabetes-related genes."Genomics 87(1):165-72.
Tunstall,R.J.,A.J.McAinch,et al.(2007)."Reduced plasma free fatty acid availability during exercise:effect on gene expression." Eur J Appl Physiol 99(5):485-93.
Tunstall,R.J.,K.A.Mehan,et al.(2002)."Exercise training increases lipid metabolism gene expression in human skeletal muscle." Am J Physiol Endocrinol Metab 283(1):E66-72.
Vavvas,D.,A.Apazidis,et al.(1997)."Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle." J Biol Chem 272(20):13255-61.
Virbasius,J.V.and R.C.Scarpulla(1994)."Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors:a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis."Proc Natl Acad Sci U S A 91(4):1309-13.
Watt,M.J.,R.J.Southgate,et al.(2004)."Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor(PPAR)alpha and delta and PPAR coactivator 1 alpha in human skeletal muscle,but not lipid regulatory genes." J Mol Endocrinol 33(2):533-44.
Winder,W.W.,E.B.Taylor,et al.(2006)."Role of AMP-activated protein kinase in the molecular adaptation to endurance exercise." Med Sci Sports Exerc 38(11):1945-9.
Wu,P.,K.Inskeep,et al.(1999)."Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes." Diabetes 48(8):1593-9.
Wu,P.,J.Sato,et al.(1998)."Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart." Biochem J 329(Pt 1):197-201.
Yang,Y.,A.Creer,et al.(2005)."Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle." J Appl Physiol 98(5):1745-52.
Akimoto,T.,S.C.Pohnert,et al.(2005)."Exercise stimulates Pgc-1 alpha transcription in skeletal muscle through activation of the p38 MAPK pathway." J Biol Chem 280(20):19587-93.
Andersson,U.and R.C.Scarpulla(2001)."Pgc-l-related coactivator,a novel,seruminducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells." Mol Cell Biol 21(11):3738-49.
Ascensao,A.A.,J.F.Magalhaes,et al.(2005)."Cardiac mitochondrial respiratory function and oxidative stress:the role of exercise." Int J Sports Med 26(4):258-67.
Atherton,P.J.,J.Babraj,et al.(2005)."Selective activation of AMPK-PGC-1 alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation." FASEB J 19(7):786-8.
Attardi,G.and G.Schatz(1988)."Biogenesis of mitochondria." Annu Rev Cell Biol 4:289-333.
Baar,K.(2004)."Involvement of PPAR gamma co-activator-1,nuclear respiratory factors 1 and 2,and PPAR alpha in the adaptive response to endurance exercise."Proc Nutr Soc 63(2):269-73.
Baar,K.and K.Esser(1999)."Phosphorylation of p70(S6k)correlates with increased skeletal muscle mass following resistance exercise." Am J Physiol 276(1 Pt 1):C120-7.
Baar,K.,A.R.Wende,et al.(2002)."Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1." FASEB J 16(14):1879-86.
Barak,Y.,D.Liao,et al.(2002)."Effects ofperoxisome proliferator-activated receptor delta on placentation,adiposity,and colorectal cancer." Proc Natl Acad Sci U S A 99(1):303-8.
Barak,Y.,M.C.Nelson,et al.(1999)."PPAR gamma is required for placental,cardiac,and adipose tissue development." Mol Cell 4(4):585-95.
Barbier,O.,I.P.Torra,et al.(2002)."Pleiotropic actions ofperoxisome proliferatoractivated receptors in lipid metabolism and atherosclerosis." Arterioscler Thromb Vasc Biol 22(5):717-26.
Bejma,J.and L.L.Ji(1999)."Aging and acute exercise enhance free radical generation in rat skeletal muscle." J Appl Physiol 87(1):465-70.
Bengtsson,J.,T.Gustafsson,et al.(2001)."Mitochondrial transcription factor A and respiratory complex Ⅳ increase in response to exercise training in humans."Pflugers Arch 443(1):61-6.
Bodine,S.C.,T.N.Stitt,et al.(2001)."Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo." Nat Cell Biol 3(11):1014-9.
Bonawitz,N.D.,M.Chatenay-Lapointe,et al.(2007)."Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression." Cell Metab 5(4):265-77.
Bonen,A.,D.J.Dyck,et al.(1999)."Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36." Am J Physiol 276(4 Pt 1):E642-9.
Braissant,O.,F.Foufelle,et al.(1996)."Differential expression ofperoxisome proliferator-activated receptors(PPARs):tissue distribution of PPAR-alpha,-beta,and -gamma in the adult rat." Endocrinology 137(1):354-66.
Bustin,S.A.and T.Nolan(2004)."Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction." J Biomol Tech 15(3):155-66.
Carter,S.L.,C.Rennie,et al.(2001)."Substrate utilization during endurance exercise in men and women after endurance training." Am J Physiol Endocrinol Metab 280(6):E898-907.
Cheung,P.C.,I.P.Salt,et al.(2000)."Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding." Biochem J 346 Pt 3:659-69.
Cho,S.H.,C.H.Lee,et al.(2004)."Redox regulation of PTEN and protein tyrosine phosphatases in H(2)O(2)mediated cell signaling." FEB S Lett 560(1-3):7-13.
Cunningham,J.T.,J.T.Rodgers,et al.(2007)."mTOR controls mitochondrial oxidative function through a YY1-PGC-lalpha transcriptional complex." Nature 450(7170):736-40.
Das,S.,J.E.Dixon,et al.(2003)."Membrane-binding and activation mechanism of PTEN." Proc Natl Aead Sci U S A 100(13):7491-6.
Daussin,F.N.,J.Zoll,et al.(2008)."Training at high exercise intensity promotes qualitative adaptations of mitochondrial function in human skeletal muscle." J Appl Physiol.
Davies,K.J.,A.T.Quintanilha,et al.(1982)."Free radicals and tissue damage produced by exercise." Biochem Biophys Res Commun 107(43:1198-205.
Denyer,G.S.,G.J.Cooney,et al.(1991)."Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex." Pflugers Arch 419(2):115-20.
Desai,B.N.,B.R.Myers,et al.(2002)."FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction." Proc Natl Acad Sci U S A 99(7):4319-24.
Dressel,U.,T.L.Allen,et al.(2003)."The peroxisome proliferator-activated receptor beta/delta agonist,GW501516,regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells." Mol Endocrinol 17(12):2477-93.
Dreyer,H.C.,S.Fujita,et al.(2006)."Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle."J Physiol 576(Pt 2):613-24.
Falkenberg,M.,M.Gaspari,et al.(2002)."Mitochondrial transcription factors B1 and B2activ ate transcription of human mtDNA." Nat G enet 31(3):289-94.
Finck,B.N.and D.P.Kelly(2006)."PGC-1 coactivators:inducible regulators of energy metabolism in health and disease." J Clin Invest 116(3):615-22.
Finkel,T.and N.J.Holbrook(2000)."Oxidants,oxidative stress and the biology of ageing." Nature 408(6809):239-47.
Gagnon,J.,T.T.Kurowski,et al.(1991)."Correlations between a nuclear and a mitochondrial mRNA of cytochrome c oxidase subunits,enzymatic activity and total mRNA content,in rat tissues." Mol Cell Biochem 107(1):21-9.
Garesse,R.and C.G.Vallejo(2001)."Animal mitochondrial biogenesis and function:a regulatory cross-talk between two genomes." Gene 263(1-2):1-16.
Glass,D.J.(2003)."Molecular mechanisms modulating muscle mass." Trends Mol Med 9(8):344-50.
Gleyzer,N.,K.Vercauteren,et al.(2005)."Control of mitochondrial transcription specificity factors(TFB1M and TFB2M)by nuclear respiratory factors(NRF-1and NRF-2)and PGC-1 family coactivators." Mol Cell Biol 25(4):1354-66.
Goto,M.,S.Terada,et al.(2000)."cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats." Biochem Biophys Res Commun 274(2):350-4.
Goto,S.,H.Naito,et al.(2007)."Hormetic effects of regular exercise in aging:correlation with oxidative stress." Appl Physiol Nutr Metab 32(5):948-53.
Gredilla,R.,A.Sanz,et al.(2001)."Caloric restriction decreases mitochondrial free radical generation at complex Ⅰ and lowers oxidative damage to mitochondrial DNA in the rat heart." FASEB J 15(9):1589-91.
Hardie,D.G.(2004)."AMP-activated protein kinase:a key system mediating metabolic responses to exercise." Med Sci Sports Exerc 36(1):28-34.
Hardie,D.G.and K.Sakamoto(2006)."AMPK:a key sensor of fuel and energy status in skeletal muscle." Physiology(Bethesda)21:48-60.
Harman,D.(1956)."Aging:a theory based on free radical and radiation chemistry." J Gerontol 11(3):298-300.
Harrington,L.S.,G.M.Findlay,et al.(2005)."Restraining PI3K:mTOR signalling goes back to the membrane." Trends Biochem Sci 30(1):35-42.
Hayashi,R.,T.Ueda,et al.(2007)."Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene." Mitochondrion 7(3):195-203.
Herrero,A.and G.Barja(1997)."Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon." Mech Ageing Dev 98(2):95-111.
Higuchi,M.,L.J.Cartier,et al.(1985)."Superoxide dismutase and catalase in skeletal muscle:adaptive response to exercise." J Gerontol 40(3):281-6.
Hildebrandt,A.L.,H.Pilegaard,et al.(2003)."Differential transcriptional activation of select metabolic genes in response to variations in exercise intensity and duration." Am J Physiol Endocfinol Metab 285(5):E1021-7.
Holloszy,J.O.(1967)."Biochemical adaptations in muscle.Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle."J Biol Chem 242(9):2278-82.
Hoist,D.,S.Luquet,et al.(2003)."Nutritional regulation and role ofperoxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle."Biochim Biophys Acta 1633(1):43-50.
Hood,D.A.,R.Zak,et al.(1989)."Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome-c-oxidase subunits." Eur J Biochem 179(2):275-80.
Hoppeler,H.,P.Luthi,et al.(1973)."The ultrastructure of the normal human skeletal muscle.A morphometric analysis on untrained men,women and well-trained orienteers." Pflugers Arch 344(3):217-32.
Horowitz,J.F.,T.C.Leone,et al.(2000)."Effect of endurance training on lipid metabolism in women:a potential role for PPARalpha in the.metabolic response to training." Am J Physiol Endocrinol Metab 279(2):E348-55.
Irrcher,I.,P.J.Adhihetty,et al.(2003)."Regulation of mitochondrial biogenesis in muscle by endurance exercise." Sports Med 33(11):783-93.
Jackson,M.J.(2008)."Free radicals generated by contracting muscle:by-products of metabolism or key regulators of muscle function?" Free Radic Biol Med 44(2):132-41.
Jackson,M.J.,R.H.Edwards,et al.(1985)."Electron spin resonance studies of intact mammalian skeletal muscle." Biochim Biophys Acta 847(2):185-90.
Jackson,M.J.,S.Papa,et al.(2002)."Antioxidants,reactive oxygen and nitrogen species,gene induction and mitochondrial function." Mol Aspects Med 23(1-3):209-85.
Jeukendmp,A.E.(2003)."Modulation of carbohydrate and fat utilization by diet,exercise and environment." Biochem Soc Trans 3 l(Pt 6):1270-3.
Ji,L.L.(2002)."Exercise-induced modulation of antioxidant defense." Ann N Y Acad Sci 959:82-92.
Ji,L.L.,F.W.Stratman,et al.(1988)."Antioxidant enzyme systems in rat liver and skeletal muscle.Influences of selenium deficiency,chronic training,and acute exercise." Arch Biochem Biophys 263(1):150-60.
Jorgensen,S.B.,T.E.Jensen,et al.(2007)."Role of AMPK in skeletal muscle gene adaptation in relation to exercise." Appl Physiol Nutr Metab 32(5):904-11.
Jorgensen,S.B.,J.T.Treebak,et al.(2007)."Role of AMPKalpha2 in basal,training-,and AICAR-induced GLUT4,hexokinase Ⅱ,and mitochondrial protein expression in mouse muscle." Am J Physiol Endocrinol Metab 292(1):E331-9.
Jorgensen,S.B.,B.Viollet,et al.(2004)."Knockout of the alpha2 but not alphal 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle." J Biol Chem 279(2):1070-9.
Judge,S.,Y.M.Jang,et al.(2005)."Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart." Am J Physiol Regul Integr Comp Physiol 289(6):R1564-72.
Kahn,B.B.,T.Alquier,et al.(2005)."AMP-activated protein kinase:ancient energy gauge provides clues to modem understanding of metabolism." Cell Metab 1(1):15-25.
Kannisto,K.,A.Chibalin,et al.(2006)."Differential expression ofperoxisomal proliferator activated receptors alpha and delta in skeletal muscle in response to changes in diet and exercise." Int J Mol Med 17(1):45-52.
Kiens,B.and E.A.Richter(1998)."Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans." Am J Physiol 275(2 Pt 1):E332-7.
Kim,D.H.,D.D.Sarbassov,et al.(2002)."mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery." Cell 110(2):163-75.
Koves,T.R.,P.Li,et al.(2005)."Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency." J Biol Chem 280(39):33588-98.
Kumar,C.T.,V.K.Reddy,et al.(1992)."Dietary supplementation of vitamin E protects heart tissue from exercise-induced oxidant stress." Mol Cell Biochem 111(1-2):109-15.
Lee,S.R.,K.S.Yang,et al.(2002)."Reversible inactivation of the tumor suppressor PTEN by H2O2." J Biol Chem 277(23):20336-42.
Lee,W.J.,M.Kim,et al.(2006)."AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1." Biochem Biophys Res Commun 340(1):291-5.
Leeuwenburgh,C.,J.Hollander,et al.(1997)."Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific." Am J Physiol 272(1 Pt 2):R363-9.
Leslie,N.R.,D.Bennett,et al.(2003)."Redox regulation of PI 3-kinase signalling via inactivation of PTEN." EMBO J 22(20):5501-10.
Li,Y.,J.S.Park,et al.(2006)."Cytochrome c oxidase subunit Ⅳ is essential for assembly and respiratory function of the enzyme complex." J Bioenerg Biomembr 38(5-6):283-91.
Lin,J.,C.Handschin,et al.(2005)."Metabolic control through the PGC-1 family of transcription coactivators." Cell Metab 1(6):361-70.
Lin,J.,H.Wu,et al.(2002)."Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres." Nature 418(6899):797-801.
Lunde,I.G.,M.Ekmark,et al.(2007)."PPARdelta expression is influenced by muscle activity and induces slow muscle properties in adult rat muscles after somatic gene transfer." J Physiol 582(Pt 3):1277-87.
Mahoney,D.J.,G.Parise,et al.(2005)."Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise." FASEB J 19(11):1498-500.
Marcil,M.,K.Bourduas,et al.(2006)."Exercise training induces respiratory substratespecific decrease in Ca2+-induced permeability transition pore opening in heart mitochondria." Am J Physiol Heart Circ Physiol 290(4):H1549-57.
Marone,J.R.,M.T.Falduto,et al.(1994)."Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle." J Appl Physiol 77(4):1685-90.
McArdle,A.and M.J.Jackson(2000)."Exercise,oxidative stress and ageing." J Anat 197 Pt 4:539-41.
McCubrey,J.A.,L.S.Steelman,et al.(2006)."Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance."Adv Enzyme Regul 46:249-79.
Meirhaeghe,A.,V.Crowley,et al.(2003)."Characterization of the human,mouse and rat PGC 1 beta(peroxisome-proliferator-activated receptor-gamma co-activator 1 beta)gene in vitro and in vivo." Biochem J 373(Pt 1):155-65.
Milan,D.,J.T.Jeon,et al.(2000)."A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle." Science 288(5469):1248-51.
Mortensen,O.H.,P.Plomgaard,et al.(2007)."PGC-lbeta is downregulated by training in human skeletal muscle:no effect of training twice every second day vs.once daily on expression of the PGC-1 family." J Appl Physiol 103(5):1536-42.
Muoio,D.M.,P.S.MacLean,et al.(2002)."Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor(PPAR)alpha knock-out mice.Evidence for compensatory regulation by PPAR delta." J Biol Chem 277(29):26089-97.
Murakami,T.,Y.Shimomura,et al.(1998)."Induction of nuclear respiratory factor-1expression by an acute bout of exercise in rat muscle." Biochim Biophys Acta 1381(1):113-22.
Navarro,A.and A.Boveris(2007)."The mitochondrial energy transduction system and the aging process." Am J Physiol Cell Physiol 292(2):C670-86.
Navarro,A.,C.Gomez,et al.(2004)."Beneficial effects of moderate exercise on mice aging:survival,behavior,oxidative stress,and mitochondrial electron transfer."Am J Physiol Regul Integr Comp Physiol 286(3):R505-11.
Nemoto,S.,K.Takeda,et al.(2000)."Role for mitochondrial oxidants as regulators of cellular metabolism." Mol Cell Biol 20(19):7311-8.
Neupert,W.(1997)."Protein import into mitochondria." Annu Rev Biochem 66:863-917.
Nielsen,J.N.,K.J.Mustard,et al.(2003)."5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle." J Appl Physiol 94(2):631-41.
Norrbom,J.,C.J.Sundberg,et al.(2004)."PGC-1 alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle." J Appl Physiol 96(1):189-94.
Ojuka,E.O.(2004)."Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle." Proc Nutr Soc 63(2):275-8.
Oliver,W.R.,Jr.,J.L.Shenk,et al.(2001)."A selective peroxisome proliferatoractivated receptor delta agonist promotes reverse cholesterol transport." Proc Natl Acad Sci U S A 98(9):5306-11.
Parker,W.D.,Jr.,J.K.Parks,et al.(2008)."Complex Ⅰ deficiency in Parkinson's disease frontal cortex." Brain Res 1189:215-8.
Parkington,J.D.,A.P.Siebert,et al.(2003)."Differential activation of mTOR signaling by contractile activity in skeletal muscle." Am J Physiol Regul Integr Comp Physiol 285(5):R1086-90.
Pawlikowska,P.,B.Gajkowska,et al.(2006)."Not only insulin stimulates mitochondriogenesis in muscle cells,but mitochondria are also essential for insulin-mediated myogenesis." Cell Prolif 39(2):127-45.
Peng,T.,T.R.Golub,et al.(2002)."The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation." Mol Cell Biol 22(15):5575-84.
Piantadosi,C.A.and H.B.Suliman(2006)."Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1." J Biol Chem 281(1):324-33.
Pilegaard,H.and P.D.Neufer(2004)."Transcriptional regulation ofpymvate dehydrogenase kinase 4 in skeletal muscle during and after exercise." Proc Nutr Soc 63(2):221-6.
Pilegaard,H.,G.A.Ordway,et al.(2000)."Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise." Am J Physiol Endocrinol Metab 279(4):E806-14.
Pilegaard,H.,B.Saltin,et al.(2003)."Exercise induces transient transcriptional activation of the PGC-1 alpha gene in human skeletal muscle." J Physiol 546(Pt 3):851-8.
Puigserver,P.,Z.Wu,et al.(1998)."A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis." Cell 92(6):829-39.
Rantanen,A.,M.Gaspari,et al.(2003)."Characterization of the mouse genes for mitochondrial transcription factors B1 and B2." Mamm Genome 14(1):1-6.
Reid,M.B.,D.S.Stokic,et al.(1994)."N-acetylcysteine inhibits muscle fatigue in humans." J Clin Invest 94(6):2468-74.
Reynolds,T.H.t.,S.C.Bodine,et al.(2002)."Control of Ser2448 phosphorylation in the mammalian target ofrapamycin by insulin and skeletal muscle load." J Biol Chem 277(20):17657-62.
Reynolds,T.H.t.,P.Reid,et al.(2004)."Effects of aerobic exercise training on the protein kinase B(PKB)/mammalian target of rapamycin(mTOR)signaling pathway in aged skeletal muscle." Exp Gerontol 39(3):379-85.
Reznick,R.M.and G.I.Shulman(2006)."The role of AMP-activated protein kinase in mitochondrial biogenesis." J Physiol 574(Pt 1):33-9.
Rossignol,R.,B.Faustin,et al.(2003)."Mitochondrial threshold effects." Biochem J 370(Pt 3):751-62.
Rossignol,R.,T.Letellier,et al.(2000)."Tissue variation in the control of oxidative phosphorylation:implication for mitochondrial diseases." Biochem J 347 Pt 1:45-53.
Russell,A.P.,J.Feilchenfeldt,et al.(2003)."Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptorgamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle." Diabetes 52(12):2874-81.
Russell,A.P.,M.K.Hesselink,et al.(2005)."Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise." FASEB J 19(8):986-8.
Sadana,P.,Y.Zhang,et al.(2007)."Regulation of carnitine palmitoyltransferase I(CPT-Ialpha)gene expression by the peroxisome proliferator activated receptor gamma coactivator(PGC-1)isoforms." Mol Cell Endocrinol 267(1-2):6-16.
Samelman,T.R.,L.J.Shiry,et al.(2000)."Endurance training increases the expression of mitochondrial and nuclear encoded cytochrome c oxidase subunits and heat shock proteins in rat skeletal muscle." Eur J Appl Physiol 83(1):22-7.
Sarbassov,D.D.,S.M.Ali,et al.(2005)."Growing roles for the mTOR pathway." Curr Opin Cell Biol 17(6):596-603.
Scarpulla,R.C.(2002)."Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian ceils." Gene 286(1):81-9.
Schieke,S.M.and T.Finkel(2006)."Mitochondrial signaling,TOR,and life span." Biol Chem 387(10-11):1357-61.
Schieke,S.M.,D.Phillips,et al.(2006)."The mammalian target of rapamycin(mTOR)pathway regulates mitochondrial oxygen consumption and oxidative capacity." J Biol Chem 281(37):27643-52.
Seip,R.L.,T.J.Angelopoulos,et al.(1995)."Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue." Am J Physiol 268(2 Pt 1):E229-36.
Shi,Y.,M.Hon,et al.(2002)."The peroxisome proliferator-activated receptor delta,an integrator of transcriptional repression and nuclear receptor signaling." Proc Natl Acad Sci USA 99(5):2613-8.
Silveira,L.R.,H.Pilegaard,et al.(2006)."The contraction induced increase in gene expression of peroxisome proliferator-activated receptor(PPAR)-gamma coactivator 1 alpha(PGC-lalpha),mitochondrial uncoupling protein 3(UCP3)and hexokinase Ⅱ(HKⅡ)in primary rat skeletal muscle cells is dependent on reactive oxygen species." Biochim Biophys Acta 1763(9):969-76.
Siu,P.M.,D.A.Donley,et al.(2004)."Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training." J Appl Physiol 97(1):277-85.
Sriwijitkamol,A.,D.K.Coletta,et al.(2007)."Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes:a time-course and dose-response study." Diabetes 56(3):836-48.
Starnes,J.W.,B.D.Barnes,et al.(2007)."Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction." J Appl Physiol 102(5):1793-8.
Steelman,L.S.,F.E.Bertrand,et al.(2004)."The complexity of PTEN:mutation,marker and potential target for therapeutic intervention." Expert Opin Ther Targets 8(6):537-50.
Suliman,H.B.,K.E.Welty-Wolf,et al.(2004)."Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis." Cardiovasc Res 64(2):279-88.
Supinski,G.(1998)."Free radical induced respiratory muscle dysfunction." Mol Cell.Biochem 179(1-2):99-110.
Terada,S.,M.Goto,et al.(2002)."Effects of low-intensity prolonged exercise on PGC-1mRNA expression in rat epitrochlearis muscle." Biochem Biophys Res Commun 296(2):350-4.
Timmons,J.A.,J.Norrbom,et al.(2006)."Expression profiling following local muscle inactivity in humans provides new perspective on diabetes-related genes."Genomics 87(1):165-72.
Tunstall,R.J.,K.A.Mehan,et al.(2002)."Exercise training increases lipid metabolism gene expression in human skeletal muscle." Am J Physiol Endocrinol Metab 283(1):E66-72.
Turrens,J.F.(2003)."Mitochondrial formation of reactive oxygen species." J Physiol 552(Pt 2):335-44.
Vasilaki,A.,A.Mansouri,et al.(2006)."Free radical generation by skeletal muscle of adult and old mice:effect of contractile activity." Aging Cell 5(2):109-17.
Vavvas,D.,A.Apazidis,et al.(1997)."Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle." J Biol Chem 272(20):13255-61.
Vazquez,F.,S.Ramaswamy,et al.(2000)."Phosphorylation of the PTEN tail regulates protein stability and function." Mol Cell Biol 20(14):5010-8.
Venditti,P.,A.Bari,et al.(2007)."Role of mitochondria in exercise-induced oxidative stress in skeletal muscle from hyperthyroid rats." Arch Biochem Biophys 463(1):12-8.
Venditti,P.,P.Masullo,et al.(1999)."Effect of training on H(2)O(2)release by mitochondria from rat skeletal muscle." Arch Biochem Biophys 372(2):315-20.
Venditti,P.,P.Masullo,et al.(2001)."Hemoproteins affect H(2)O(2)removal from rat tissues." Int J Biochem Cell Biol 33(3):293-301.
Virbasius,J.V.and R.C.Scarpulla(1994)."Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors:a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis."Proc Natl Acad Sci U S A 91(4):1309-13.
Watt,M.J.,R.J.Southgate,et al.(2004)."Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor(PPAR)alpha and delta and PPAR coactivator lalpha in human skeletal muscle,but not lipid regulatory genes." J Mol Endocrinol 33(2):533-44.
White,R.J.(2004)."A "radical" idea comes of age:mitochondrial oxidant signaling in health and disease." J Mol Cell Cardiol 37(6):1115-7.
Williams,R.S.,M.Garcia-Moll,et al.(1987)."Adaptation of skeletal muscle to increased contractile activity.Expression nuclear genes encoding mitochondrial proteins." J Biol Chem 262(6):2764-7.
Williamson,D.L.,N.Kubica;et al.(2006)."Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target ofrapamycin(mTOR)signalling to regulatory mechanisms of mRNA translation in mouse muscle." J Physiol 573(Pt 2):497-510.
Winder,W.W.,E.B.Taylor,et al.(2006)."Role of AMP-activated protein kinase in the molecular adaptation to endurance exercise." Med Sci Sports Exerc 38(11):1945-9.
Wu,P.,K.Inskeep,et al.(1999)."Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes." Diabetes 48(8):1593-9.
Wu,P.,J.Sato,et al.(1998)."Starvation and diabetes increase the amount ofpyruvate dehydrogenase kinase isoenzyme 4 in rat heart." Biochem J 329(Pt 1):197-201.
Wullschleger,S.,R.Loewith,et al.(2006)."TOR signaling in growth and metabolism."Cell 124(3):471-84.
丁树哲(2001).“有氧运动训练后大鼠横纹肌线粒体DNA含量观察.”中国运动医堂杂志20(4):3.
丁树哲(2002)。”有氧运动对线粒体质子跨膜转运及核糖核苷二磷酸还原酶的影响.”中国运动医学杂志21(3):244-247.
Adhihetty,P.J.,I.Irrcher,et al.(2003)."Plasticity of skeletal muscle mitochondria in response to contractile activity." Exp Physiol 88(1):99-107.
Akimoto,T.,S.C.Pohnert,et al.(2005)."Exercise stimulates Pgc-lalpha transcription in skeletal muscle through activation of the p38 MAPK pathway." J Biol Chem 280(20):19587-93.
Ascensao,A.A.,J.F.Magalhaes,et al.(2005)."Cardiac mitochondrial respiratory function and oxidative stress:the role of exercise." Int J Sports Med 26(4):258-67.
Atherton,P.J.,J.Babraj,et al.(2005)."Selective activation of AMPK-PGC-lalpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation." FASEB J 19(7):786-8.
Baar,K.and K.Esser(1999)."Phosphorylation ofp70(S6k)correlates with increased skeletal muscle mass following resistance exercise." Am J Physio1276(1 Pt 1):C120-7.
Baar,K.,A.R.Wende,et al.(2002)."Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1." FASEB J 16(14):1879-86.
Bejma,J.and L.L.Ji(1999)."Aging and acute exercise enhance free radical generation in rat skeletal muscle." J Appl Physiol 87(1):465-70.
Bengtsson,J.,T.Gustafsson,et al.(2001)."Mitochondrial transcription factor A and respiratory complex Ⅳ increase in response to exercise training in humans."Pflugers Arch 443(1):61-6.
Bodine,S.C.,T.N.Stitt,et al.(2001)."Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo." Nat Cell Biol 3(11):1014-9.
Bonawitz,N.D.,M.Chatenay-Lapointe,et al.(2007)."Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression." Cell Metab 5(4):265-77.
Cho,S.H.,C.H.Lee,et al.(2004)."Redox regulation of PTEN and protein tyrosine phosphatases in H(2)O(2)mediated cell signaling." FEBS Lett 560(1-3):7-13.
Cunningham,J.T.,J.T.Rodgers,et al.(2007).,mTOR controls mitochondrial oxidative function through a YY1-PGC-lalpha transcriptional complex." Nature 450(7170):736-40.
Das,S.,J.E.Dixon,et al.(2003)."Membrane-binding and activation mechanism of PTEN." Proc Natl Acad Sci U S A 100(13):7491-6.
Daussin,F.N.,J.Zoll,et al.(2008)."Training at high exercise intensity promotes qualitative adaptations of mitochondrial function in human skeletal muscle." J Appl Physiol.
Davies,K.J.,A.T.Quintanilha,et al.(1982)."Free radicals and tissue damage produced by exercise." Biochem Biophys Res Commun 107(4):1198-205.
Desai,B.N.,B.R.Myers,et al.(2002)."FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction." Proc Natl Acad Sci U S A 99(7):4319-24.
Dreyer,H.C.,S.Fujita,et al.(2006)."Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle."J Physiol 576(Pt 2):613-24.
Gagnon,J.,T.T.Kurowski,et al.(1991)."Correlations between a nuclear and a mitochondrial mRNA of cytochrome c oxidase subunits,enzymatic activity and total mRNA content,in rat tissues." Mol Cell Biochem 107(1):21-9.
Garesse,R.and C.G.Vallejo(2001)."Animal mitochondrial biogenesis and function:a regulatory cross-talk between two genomes." Gene 263(1-2):1-16.
Goto,M.,S.Terada,et al.(2000)."cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats." Biochem Biophys Res Commun 274(2):350-4.
Goto,S.,H.Naito,et al.(2007)."Hormetic effects of regular exercise in aging:correlation with oxidative stress." Appl Physiol Nutr Metab 32(5):948-53.
Gredilla,R.,A.Sanz,et al.(2001)."Caloric restriction decreases mitochondrial free radical generation at complex Ⅰ and lowers oxidative damage to mitochondrial DNA in the rat heart." FASEB J 15(9):1589-91.
Harrington,L.S.,G.M.Findlay,et al.(2005)."Restraining PI3K:mTOR signalling goes.back to the membrane." Trends Biochem Sci 30(1):35-42.
Herrero,A.and G.Barja(1997)."Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon." Mech Ageing Dev 98(2):95-111.
Higuchi,M.,L.J.Cartier,et al.(1985)."Superoxide dismutase and catalase in skeletal muscle:adaptive response to exercise." J Gerontol 40(3):281-6.
Holloszy,J.O.(1967)."Biochemical adaptations in muscle.Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle."J Biol Chem 242(9):2278-82.
Hood,D.A.and A.Saleem(2007)."Exercise-induced mitochondrial biogenesis in skeletal muscle." Nutr Metab Cardiovasc Dis 17(5):332-7.
Hood,D.A.,R.Zak,et al.(1989)."Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome-coxidase subunits." Eur J Biochem 179(2):275-80.
Hoppeler,H.,P.Luthi,et al.(1973)."The ultrastructure of the normal human skeletal muscle.A morphometric analysis on untrained men,women and well-trained orienteers." Pflugers Arch 344(3):217-32.
Irrcher,I.,P.J.Adhihetty,et al.(2003)."Regulation ofmitochondrial biogenesis in muscle by endurance exercise." Sports Med 33(11):783-93.
Jackson,M.J.(2008)."Free radicals generated by contracting muscle:by-products of metabolism or key regulators of muscle function?" Free Radic Biol Med 44(2):132-41.
Jackson,M.J.,R.H.Edwards,et al.(1985)."Electron spin resonance studies of intact mammalian skeletal muscle." Biochim Biophys Acta 847(2):185-90.
Ji,L.L.,F.W.Stratman,et al.(1988)."Antioxidant enzyme systems in rat liver and skeletal muscle.Influences of selenium deficiency,chronic training,and acute exercise." Arch Biochem Biophys 263(1):150-60.
Judge,S.,Y.M.Jang,et al.(2005)."Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart." Am J Physiol Regul Integr Comp Physiol 289(6):R1564-72.
Kumar,C.T.,V.K.Reddy,et al.(1992)."Dietary supplementation of vitamin E protects heart tissue from exercise-induced oxidant stress." Mol Cell Biochem 111(1-2):109-15.
Lee,S.R.,K.S.Yang,et al.(2002)."Reversible inactivation of the tumor suppressor PTEN by H2O2." J Biol Chem 277(23):20336-42.
Leeuwenburgh,C.,J.Hollander,et al.(1997)."Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific." Am J Physiol 272(1 Pt 2):R363-9.
Leslie,N.R.,D.Bennett,et al.(2003)."Redox regulation of PI 3-kinase signalling via inactivation ofPTEN." EMBO J 22(20):5501-10.
Marcil,M.,K.Bourduas,et al.(2006)."Exercise training induces respiratory substratespecific decrease in Ca2+-induced permeability transition pore opening in heart mitochondfia." Am J Physiol Heart Circ Physiol 290(4):H1549-57.
Marone,J.R.,M.T.Falduto,et al.(1994)."Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle." J Appl Physiol 77(4):1685-90.
McArdle,A.and M.J.Jackson(2000)."Exercise,oxidative stress and ageing." J Anat 197 Pt 4:539-41.
McCubrey,J.A.,L.S.Steelman,et al.(2006)."Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance."Adv Enzyme Regul 46:249-79.
Navarro,A.,C.Gomez,et al.(2004)."Beneficial effects of moderate exercise on mice aging:survival,behavior,oxidative stress,and mitochondrial electron transfer."Am J Physiol Regul Integr Comp Physiol 286(3):R505-11.
Parker,W.D.,Jr.,J.K.Parks,et al.(2008)."Complex Ⅰ deficiency in Parkinson's disease frontal cortex." Brain Res 1189:215-8.
Parkington,J.D.,A.P.Siebert,et al.(2003)."Differential activation ofmTOR signaling by contractile activity in skeletal muscle." Am J Physiol Regul Integr Comp Physiol 285(5):R1086-90.
Pawlikowska,P.,B.Gajkowska,et al.(2006)."Not only insulin stimulates mitochondriogenesis in muscle cells,but mitochondria are also essential for insulin-mediated myogenesis." Cell Prolif 39(2):127-45.
Peng,T.,T.R.Golub,et al.(2002)."The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation." Mol Cell Biol 22(15):5575-84.
Piantadosi,C.A.and H.B.Suliman(2006)."Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1." J Biol Chem 281(1):324-33.
Reid,M.B.,D.S.Stokic,et al.(1994)."N-acetylcysteine inhibits muscle fatigue in humans." J Clin Invest 94(6):2468-74.
Reynolds,T.H.t.,S.C.Bodine,et al.(2002)."Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load." J Biol Chem 277(20):17657-62.
Reynolds,T.H.t.,P.Reid,et al.(2004)."Effects of aerobic exercise training on the protein kinase B(PKB)/mammalian target ofrapamycin(mTOR)signaling pathway in aged skeletal muscle." Exp Gerontol 39(3):379-85.
Rossignol,R.,B.Faustin,et al.(2003)."Mitochondrial threshold effects." Biochem J 370(Pt 3):751-62.
Rossignol,R.,T.Letellier,et al.(2000)."Tissue variation in the control of oxidative phosphorylation:implication for mitochondrial diseases." Biochem J 347 Pt 1:45-53.
Samelman,T.R.,L.J.Shiry,et al.(2000)."Endurance training increases the expression of mitochondrial and nuclear encoded cytochrome c oxidase subunits and heat shock proteins in rat skeletal muscle." Eur J Appl Physiol 83(1):22-7.
Sarbassov,D.D.,S.M.Ali,et al.(2005)."Growing roles for the mTOR pathway." Curr Opin Cell Biol 17(6):596-603.
Scarpulla,R.C.(2002)."Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells." Gene 286(1):81-9.
Schieke,S.M.and T.Finkel(2006)."Mitochondrial signaling,TOR,and life span." Biol Chem 387(10-11):1357-61.
Schieke,S.M.,D.Phillips,et al.(2006)."The mammalian target ofrapamycin(mTOR)pathway regulates mitochondrial oxygen consumption and oxidative capacity." J Biol Chem 281(37):27643-52.
Silveira,L.R.,H.Pilegaard,et al.(2006)."The contraction induced increase in gene expression ofperoxisome proliferator-activated receptor(PPAR)-gamma coactivator lalpha(PGC-lalpha),mitochondrial uncoupling protein 3(UCP3)and hexokinase Ⅱ(HKⅡ)in primary rat skeletal muscle cells is dependent on reactive oxygen species." Biochim Biophys Acta 1763(9):969-76.
Starnes,J.W.,B.D.Barnes,et al.(2007)."Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction." J Appl Physiol 102(5):1793-8.
Steelman,L.S.,F.E.Bertrand,et al.(2004)."The complexity of PTEN:mutation,marker and potential target for therapeutic intervention." Expert Opin Ther Targets 8(6):537-50.
Suliman,H.B.,K.E.Welty-Wolf,et al.(2004)."Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis." Cardiovasc Res 64(2):279-88.
Terada,S.,M.Goto,et al.(2002)."Effects of low-intensity prolonged exercise on PGC-1mRNA expression in rat epitrochlearis muscle." Biochem Biophys Res Commun 296(2):350-4.
Turrens,J.F.(2003)."Mitochondrial formation of reactive oxygen species." J Physiol 552(Pt 2):335-44.
Vasilaki,A.,A.Mansouri,et al.(2006)."Free radical generation by skeletal muscle of adult and old mice:effect of contractile activity." Aging Cell 5(2):109-17.
Vazquez,F.,S.Ramaswamy,et al.(2000)."Phosphorylation of the PTEN tail regulates protein stability and function." Mol Cell Biol 20(14):5010-8.
Venditti,P.,A.Bari,et al.(2007)."Role ofmitochondria in exercise-induced oxidative stress in skeletal muscle from hyperthyroid rats." Arch Biochem Biophys 463(1):12-8.
Venditti,P.,P.Masullo,et al.(1999)."Effect of training on H(2)O(2)release by mitochondria from rat skeletal muscle." Arch Biochem Biophys 372(2):315-20.
Venditti,P.,P.Masullo,et al.(2001)."Hemoproteins affect H(2)O(2)removal from rat tissues." Int J Biochem Cell Biol 33(3):293-301.
White,R.J.(2004)."A "radical" idea comes of age:mitochondrial oxidant signaling in health and disease." J Mol Cell Cardiol 37(6):1115-7.
Williams,R.S.,M.Garcia-Moll,et al.(1987)."Adaptation of skeletal muscle to increased contractile activity.Expression nuclear genes encoding mitochondrial proteins." J Biol Chem 262(6):2764-7.
Williamson,D.L.,N.Kubica,et al.(2006)."Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin(mTOR)signalling to regulatory mechanisms of mRNA translation in mouse muscle." J Physiol 573(Pt 2):497-510.
Wullschleger,S.,R.Loewith,et al.(2006)."TOR signaling in growth and metabolism."Cell 124(3):471-84.
丁树哲(2001).“有氧运动训练后大鼠横纹肌线粒体DNA含量观察.”中国运动医学杂志20(4):3.
丁树哲(2002),“有氧运动对线粒体质子跨膜转运及核糖核苷二磷酸还原酶的影响.”中国运动医学杂志21(3):244—247.
Adhihetty,P.J.,I.Irrcher,et al.(2003)."Plasticity of skeletal muscle mitochondria in response to contractile activity." Exp Physiol 88(1):99-107.
Akimoto,T.,S.C.Pohnert,et al.(2005)."Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway." J Biol Chem 280(20):19587-93.
Andersson,U.and R.C.Scarpulla(2001)."Pgc-1-related coactivator,a novel,seruminducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells." Mol Cell Biol 21(11):3738-49.
Atherton,P.J.,J.Babraj,et al.(2005)."Selective activation of AMPK-PGC-1 alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation." FASEB J 19(7):786-8.
Baar,K.(2004)."Involvement of PPAR gamma co-activator-1,nuclear respiratory factors 1 and 2,and PPAR alpha in the adaptive response to endurance exercise."Proc Nutr Soc 63(2):269-73.
Baar,K.,A.R.Wende,et al.(2002)."Adaptations of skeletal muscle to exercise:rapid increase in the transcriptional coactivator PGC-1." FASEB J 16(14):1879-86.
Bahr,R.,A.T.Hostmark,et al.(1991)."Effect of exercise on recovery changes in plasma levels of FFA,glycerol,glucose and catecholamines." Acta Physiol Scand 143(1):105-15.
Barak,Y.,D.Liao,et al.(2002)."Effects of peroxisome proliferator-activated receptor delta on placentation,adiposity,and colorectal cancer." Proc Natl Acad Sci U S A 99(1):303-8.
Barak,Y.,M.C.Nelson,et al.(1999)."PPAR gamma is required for placental,cardiac,and adipose tissue development." Mol Cell 4(4):585-95.
Barbier,O.,I.P.Torra,et al.(2002)."Pleiotropic actions of peroxisome proliferatoractivated receptors in lipid metabolism and atherosclerosis." Arterioscler Thromb Vasc Biol 22(5):717-26.
Bengtsson,J.,T.Gustafsson,et al.(2001)."Mitochondrial transcription factor A and respiratory complex Ⅳ increase in response to exercise training in humans."Pflugers Arch 443(1):61-6.
Bickel,C.S.,J.Slade,et al.(2005)."Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise." J Appl Physiol 98(2):482-8.
Bonen,A.,D.J.Dyck,et al.(1999)."Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36." Am J Physiol 276(4 Pt 1):E642-9.
Braissant,O.,F.Foufelle,et al.(1996)."Differential expression of peroxisome proliferator-activated receptors(PPARs):tissue distribution of PPAR-alpha,-beta,and -gamma in the adult rat." Endocrinology 137(1):354-66.
Bustin,S.A.and T.Nolan(2004)."Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction." J Biomol Tech 15(3):155-66.
Carter,S.L.,C.Rennie,et al.(2001)."Substrate utilization during endurance exercise in men and women after endurance training." Am J Physiol Endocrinol Metab 280(6):E898-907.
Cheung,P.C.,I.P.Salt,et al.(2000)."Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding." Biochem J 346 Pt 3:659-69.
Denyer,G.S.,G.J.Cooney,et al.(1991)."Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex." Pflugers Arch 419(2):115-20.
Dressel,U.,T.L.Allen,et al.(2003)."The peroxisome proliferator-activated receptor beta/delta agonist,GW501516,regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells." Mol Endocrinol 17(12):2477-93.
Falkenberg,M.,M.Gaspari,et al.(2002)."Mitochondrial transcription factors B1 and B2activate transcription of human mtDNA." Nat Genet 31(3):289-94.
Finck,B.N.and D.P.Kelly(2006)."PGC-1 coactivators:inducible regulators of energy metabolism in health and disease." J Clin Invest 116(3):615-22.
Frosig,C.,S.B.Jorgensen,et al.(2004)."5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle."Am J Physiol Endocrinol Metab 286(3):E411-7.
Gaudet-Savard,T.,A.Ferland,et al.(2007)."Safety and magnitude of changes in blood glucose levels following exercise performed in the fasted and the postprandial state in men with type 2 diabetes." Eur J Cardiovasc Prey Rehabil 14(6):831-6.
Glass,D.J.(2003)."Molecular mechanisms modulating muscle mass." Trends Mol Med 9(8):344-50.
Gleyzer,N.,K.Vercauteren,et al.(2005)."Control of mitochondrial transcription specificity factors(TFB1M and TFB2M)by nuclear respiratory factors(NRF-1and NRF-2)and PGC-1 family coactivators." Mol Cell Biol 25(4):1354-66.
Gordon,J.W.,A.A.Rungi,et al.(2001)."Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle." J Appl Physiol 90(1):389-96.
Goto,M.,S.Terada,et al.(2000)."cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming-exercised rats." Biochem Biophys Res Commun 274(2):350-4.
Green,H.J.,D.J.Barr,et al.(2004)."Malleability of human skeletal muscle Na(+)-K(+)-ATPase pump with short-term training." J.Appl Physiol 97(1):143-8.
Hardie,D.G.(2004)."AMP-activated protein kinase:a key system mediating metabolic responses to exercise." Med Sci Sports Exerc 36(1):28-34.
Hardie,D.G.and K.Sakamoto(2006)."AMPK:a key sensor of fuel and energy status in skeletal muscle." Physiology(Bethesda)21:48-60.
Hayashi,R.,T.Ueda,et al.(2007)."Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene." Mitochondrion 7(3):195-203.
Hildebrandt,A.L.,H.Pilegaard,et al.(2003)."Differential transcriptional activation of select metabolic genes in response to variations in exercise intensity and duration." Am J Physiol Endocrinol Metab 285(5):E1021-7.
Holst,D.,S.Luquet,et al.(2003)."Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle."Biochim Biophys Acta 1633(1):43-50.
Hood,D.A.,M.Takahashi,et al.(2000)."Assembly of the cellular powerhouse:current issues in muscle mitochondrial biogenesis." Exerc Sport Sci Rev 28(2):68-73.
Horowitz,J.F.,T.C.Leone,et al.(2000)."Effect of endurance training on lipid metabolism in women:a potential role for PPARalpha in the metabolic response to training." Am J Physiol Endocrinol Metab 279(2):E348-55.
Jeukendrup,A.E.(2003)."Modulation of carbohydrate and fat utilization by diet,exercise and environment." Biochem Soc Trans 31(Pt 6):1270-3.
Ji,L.L.(2002)."Exercise-induced modulation of antioxidant defense." Ann N Y Acad Sci 959:82-92.
Jorgensen,S.B.,T.E.Jensen,et al.(2007)."Role of AMPK in skeletal muscle gene adaptation in relation to exercise." Appl Physiol Nutr Metab 32(5):904-11.
Jorgensen,S.B.,J.T.Treebak,et al.(2007)."Role of AMPKalpha2 in basal,training-,and AICAR-induced GLUT4,hexokinase Ⅱ,and mitochondrial protein expression in mouse muscle." Am J Physiol Endocrinol Metab 292(1):E331-9.
Jorgensen,S.B.,B.Viollet,et al.(2004)."Knockout of the alpha2 but not alphal 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle." J Biol Chem 279(2):1070-9.
Kahn,B.B.,T.Alquier,et al.(2005)."AMP-activated protein kinase:ancient energy gauge provides clues to modern understanding of metabolism." Cell Metab 1(1):15-25.
Kannisto,K.,A.Chibalin,et al.(2006)."Differential expression of peroxisomal proliferator activated receptors alpha and delta in skeletal muscle in response to changes in diet and exercise." Int J Mol Med 17(1):45-52.
Kiens,B.and E.A.Richter(1998)."Utilization of skeletal muscle triacylglycerol during postexercise recovery in humans." Am J Physiol 275(2 Pt 1):E332-7.
Koves,T.R.,P.Li,et al.(2005)."Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency." J Biol Chem 280(39):33588-98.
Lee,W.J.,M.Kim,et al.(2006)."AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1." Biochem Biophys Res Commun 340(1):291-5.
Lin,J.,C.Handschin,et al.(2005)."Metabolic control through the PGC-1 family of transcription coactivators." Cell Metab 1(6):361-70.
Lin,J.,H.Wu,et al.(2002)."Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres." Nature 418(6899):797-801.
Lunde,I.G.,M.Ekmark,et al.(2007)."PPARdelta expression is influenced by muscle activity and induces slow muscle properties in adult rat muscles after somatic gene transfer." J Physiol 582(Pt 3):1277-87.
Mahoney,D.J.,G.Parise,et al.(2005)."Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise." FASEB J 19(11):1498-500.
Marion-Latard,F.,F.Crampes,et al.(2003)."Post-exercise increase of lipid oxidation after a moderate exercise bout in untrained healthy obese men." Horm Metab Res 35(2):97-103.
MAUD,P.C.F.,Ed.(1995).Physiological Assessment of Human Fitness.Champaign,IL:Human Kinetics,.
Meirhaeghe,A.,V.Crowley,et al.(2003)."Characterization of the human,mouse and rat PGC1 beta(peroxisome-proliferator-activated receptor-gamma co-activator 1 beta)gene in vitro and in vivo." Biochem J 373(Pt 1):155-65.
Milan,D.,J.T.Jeon,et al.(2000)."A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle." Science 288(5469):1248-51.
Mortensen,O.H.,P.Plomgaard,et al.(2007)."PGC-lbeta is downregulated by training in human skeletal muscle:no effect of training twice every second day vs.once daily on expression of the PGC-1 family." J Appl Physiol 103(5):1536-42.
Muoio,D.M.,P.S.MacLean,et al.(2002)."Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor(PPAR)alpha knock-out mice.Evidence for compensatory regulation by PPAR delta." J Biol Chem 277(29):26089-97.
Murakami,T.,Y.Shimomura,et al.(1998)."Induction of nuclear respiratory factor-1expression by an acute bout of exercise in rat muscle." Biochim Biophys Acta 1381(1):113-22.
Nielsen,J.N.,K.J.Mustard,et al.(2003)."5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle." J Appl Physiol 94(2):631-41.
Norrbom,J.,C.J.Sundberg,et al.(2004)."PGC-1 alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle." J Appl Physiol 96(1):189-94.
Ojuka,E.O.(2004)."Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle." Proc Nutr Soc 63(2):275-8.
Oliver,W.R.,Jr.,J.L.Shenk,et al.(2001)."A selective peroxisome proliferatoractivated receptor delta agonist promotes reverse cholesterol transport." Proc Natl Acad Sci U S A 98(9):5306-11.
Pilegaard,H.and P.D.Neufer(2004)."Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise." Proc Nutr Soc 63(2):221-6.
Pilegaard,H.,G.A.Ordway,et al.(2000)."Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise." Am J Physiol Endocrinol Metab 279(4):E806-14.
Pilegaard,H.,B.Saltin,et al.(2003)."Exercise induces transient transcriptional activation of the PGC-1 alpha gene in human skeletal muscle." J Physiol 546(Pt 3):851-8.
Puigserver,P.,Z.Wu,et al.(1998)."A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis." Cell 92(6):829-39.
Rantanen,A.,M.Gaspari,et al.(2003)."Characterization of the mouse genes for mitochondrial transcription factors B1 and B2." Mamm Genome 14(1):1-6.
Rantzau,C.,M.Christopher,et al.(2008)."Contrasting effects of exercise,AICAR,and increased fatty acid supply on in vivo and skeletal muscle glucose metabolism." J Appl Physiol 104(2):363-70.
Reznick,R.M.and G.I.Shulman(2006)."The role of AMP-activated protein kinase in mitochondrial biogenesis." J Physiol 574(Pt 1):33-9.
Russell,A.P.,J.Feilchenfeldt,et al.(2003)."Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor- gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle." Diabetes 52(12):2874-81.
Russell,A.P.,M.K.Hesselink,et al.(2005)."Regulation of metabolic transcriptional coactivators and transcription factors with acute exercise." FASEB J 19(8):986-8.
Sadana,P.,Y.Zhang,et al.(2007)."Regulation of carnitine palmitoyltransferase Ⅰ(CPTIalpha)gene expression by the peroxisome proliferator activated receptor gamma coactivator(PGC-1)isoforms." Mol Cell Endocrinol 267(1-2):6-16.
Sari,R.,M.K.Balci,et al.(2007)."Acute effect of exercise on plasma leptin level and insulin resistance in obese women with stable caloric intake." Endocr Res 32(1-2):9-17.
Scarpulla,R.C.(2002)."Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells." Gene 286(1):81-9.
Seip,R.L.,T.J.Angelopoulos,et al.(1995)."Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue." Am J Physiol 268(2 Pt 1):E229-36.
Shi,Y.,M.Hon,et al.(2002)."The peroxisome proliferator-activated receptor delta,an integrator of transcriptional repression and nuclear receptor signaling." Proc Natl Acad Sci U S A 99(5):2613-8.
Siu,P.M.,D.A.Donley,et al.(2004)."Myogenin and oxidative enzyme gene expression levels are elevated in rat soleus muscles after endurance training." J Appl Physiol 97(1):277-85.
Sriwijitkamol,A.,D.K.Coletta,et al.(2007)."Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes:a time-course and dose-response study." Diabetes 56(3):836-48.
Terada,S.,M.Goto,et al.(2002)."Effects of low-intensity prolonged exercise on PGC-1mRNA expression in rat epitrochlearis muscle." Biochem Biophgs Res Commun 296(2):350-4.
Timmons,J.A.,J.Norrbom,et al.(2006)."Expression profiling following local muscle inactivity in humans provides new perspective on diabetes-related genes."Genomics 87(1):165-72.
Tunstall,R.J.,A.J.McAinch,et al.(2007)."Reduced plasma free fatty acid availability during exercise:effect on gene expression." Eur J Appl Physiol 99(5):485-93.
Tunstall,R.J.,K.A.Mehan,et al.(2002)."Exercise training increases lipid metabolism gene expression in human skeletal muscle." Am J Physiol Endocrinol Metab 283(1):E66-72.
Vavvas,D.,A.Apazidis,et al.(1997)."Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle." J Biol Chem 272(20):13255-61.
Virbasius,J.V.and R.C.Scarpulla(1994)."Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors:a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis."Proc Natl Acad Sci U S A 91(4):1309-13.
Watt,M.J.,R.J.Southgate,et al.(2004)."Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor(PPAR)alpha and delta and PPAR coactivator 1 alpha in human skeletal muscle,but not lipid regulatory genes." J Mol Endocrinol 33(2):533-44.
Winder,W.W.,E.B.Taylor,et al.(2006)."Role of AMP-activated protein kinase in the molecular adaptation to endurance exercise." Med Sci Sports Exerc 38(11):1945-9.
Wu,P.,K.Inskeep,et al.(1999)."Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes." Diabetes 48(8):1593-9.
Wu,P.,J.Sato,et al.(1998)."Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart." Biochem J 329(Pt 1):197-201.
Yang,Y.,A.Creer,et al.(2005)."Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle." J Appl Physiol 98(5):1745-52.