能量限制与白藜芦醇对U937泡沫细胞CD36、SIRT1、SIRT3表达影响的比较研究
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摘要
背景
动脉粥样硬化性疾病已经成为威胁人类健康的主要疾病,单核巨噬细胞源性的泡沫细胞是粥样斑块早期形成阶段的典型病变,贯穿于动脉粥样硬化疾病的发生发展。单核细胞源性泡沫细胞上的清道夫受体CD36能识别、内吞氧化型低密度脂蛋白,而氧化型低密度脂蛋白又通过诱导CD36的高表达来刺激其对本身的摄取,形成正反馈,造成胆固醇在细胞内不断积累,最终导致泡沫细胞的形成。泡沫细胞形成后,CD36高表达能诱导单核巨噬细胞向粥样斑块粘附聚集,并参与血管壁的炎症反应,引起动脉粥样硬化的进一步发展。能量限制和白藜芦醇在许多实验中已证实有一定的抗动脉粥样硬化作用,而且研究证实它们均能调节沉默信息调节因子2(Sir2)的表达,我们希望以建立单核巨噬细胞源性泡沫细胞模型为研究的切入点,初步探讨能量限制和白藜芦醇在调节泡沫细胞CD36方面的作用及有关机制。
目的
初步探讨能量限制(calorie restriction,CR)对于单核巨噬细胞源性泡沫细胞清道夫受体CD36的抑制效果及调控通路以及白藜芦醇(resveratrol,Res)是否能完全模拟出CR效果及其原因所在,进行对比实验观察CR与Res对于人U937泡沫细胞CD36和长寿基因SIRT1与SIRT3 mRNA表达的影响。
方法
1.当人U937细胞长至1.0×10~6个/ml后,用终浓度为100ng/ml的佛波酯(phorbol 12-myristate 13-acetate,PMA)和终浓度为80μg/ml的人氧化型低密度脂蛋白(ox-LDL)刺激48h,油红O染色后光镜下可见细胞胞浆内存在大量的脂滴,符合泡沫细胞的形态特征,U937泡沫细胞模型建立。
2.分别用含不同浓度白藜芦醇的培养基培养细胞密度为1.0×10~6个/ml的U937泡沫细胞24小时,并利用四氮唑蓝检测法(MTT)和流式细胞计数检测法(FCM)确定一个对于细胞损伤较小且效果最好的药物作用浓度。
3.U937泡沫细胞模型建立后,随机分为四组:分别用高糖DMEM(泡沫细胞模型组)、低糖DMEM(CR组)、高糖DMEM加白藜芦醇(Res药物组)、高糖DMEM加白藜芦醇与尼克酰胺(Res药物对照组)四种培养基继续培养泡沫细胞48小时。
4.分别提取各组细胞内mRNA,进行逆转录PCR检测,观察各组间泡沫细胞清道夫受体CD36和长寿基因SIRT1、SIRT3的mRNA表达水平情况。
结果
1.MTT和FCM的检测结果显示,20μM白藜芦醇是一个比较合适的药物作用浓度。
2.与泡沫细胞模型组对比,CR组CD36 mRNA表达显著降低(P<0.01),Res药物组CD36 mRNA表达降低(P<0.05),Res药物对照组CD36 mRNA表达没有显著变化(P﹥0.05);与Res药物组对比,CR组CD36 mRNA表达降低(P<0.05)。
3.与泡沫细胞模型组对比,CR组SIRT1 mRNA表达增加(P<0.05), Res药物组SIRT1 mRNA表达显著增加(P<0.01),Res药物对照组SIRT1 mRNA表达没有显著变化(P﹥0.05);与CR组对比,Res药物组SIRT1 mRNA表达增加(P<0.05)。
4.与泡沫细胞模型组对比,CR组SIRT3 mRNA表达增加(P<0.05),Res药物组SIRT3 mRNA表达没有显著变化(P﹥0.05),Res药物对照组SIRT3 mRNA表达没有显著变化(P﹥0.05);与CR组对比,Res药物组SIRT3 mRNA表达降低(P<0.05)。
结论
1. CR能使U937泡沫细胞长寿基因SIRT1及SIRT3的mRNA表达水平上调,清道夫受体CD36的mRNA表达水平下调,对于泡沫细胞的发展有抑制作用。
2.白藜芦醇能使长寿基因SIRT1 mRNA表达水平上调,但对SIRT3 mRNA的表达水平无显著影响,同时通过上调SIRT1的表达使U937泡沫细胞清道夫受体CD36的mRNA表达水平下调。
3. CR和白藜芦醇对泡沫细胞上Sir2家族成员的调节是不同的,而且白藜芦醇对泡沫细胞上CD36的抑制作用不如CR,CR可能还存在除SIRT1以外的途径抑制CD36。
Background
Atherosclerotic disease has become the major disease threatens human health,the foam cells generating from mononuclear macrophage are the classical modification in the early stage and propagating in the pathology of atherosclerosis. The CD36 of scavenger receptors on the foam cells generating from monocytes can recognize and swallow ox-LDL,on the other hand the ox-LDL can induce the highly expression of CD36 and than stimulate the uptake of itself, forming the positive feedback loop which lead to the accumulation of cholesterol in the cell and result in the formation of foam cell. After the generation of foma cells, the highly expression of CD36 can induce the monocytes adhere to atheromatous plaque and participate in the inflammation process of vescular wall leading to the propagation of atherosclerosis. Several studies have already proved that calorie restriction and resveratrol have the effect of anti-atherosclerosis and regulate the expression of Sir2. We hope to run a reserch based on the model of foam cell generating from mononuclear macrophage, discuss the function and related mechanisms of CR and Res in the regulation of CD36 in foam cells.
Objective
To discuss the inhibitory effect and regulation passways of CR on the CD36 of scavenger receptors in the foam cell generating from monocytes. To find out the possibility and potential mechanism of resveratrol mimic the function of CR. To investigate the influence on the expression of CD36 on human U937 foam cell and mRNA of long life gene SIRT1 and SIRT3.
Methods
1. When the amonut of human U937 cells come to 1.0×106 /ml, using the final concentration of 100ng/ml of the phorbol 12-myristate 13-acetate and the final concentration of 80ug/ml of human ox-LDL stimulate cells for 48 hours,after oil red O staining,a large mount of lipid droplet can be viewed in the cytoplasm,which correspond to the morphological feature of foma cell,so that establishe the model of human U937 foam cell.
2. The U937 foam cells in the density of 1.0×106 /ml are cultured in the different concentration of resveratrol culture medium for 24 hours. To find out the best drug concentration which has less injuryed cell,us the MTT and FCM.
3. After establishing the model of U937 foma cell,using four kinds of culture mediums which are high glucose DMEM、low glucose DMEM、high glucose DMEM combine with resveratrol and high glucose combine with resveratrol and nicotimamide continue to culture cell for another 48 hours. And then randomly divide into four groups:①foam cell model②CR group③Res durg group④Res durg control group.
4. To extract the mRNA from the above groups respectively,detect the reverse transportation PCR and examine the expression level of CD36 on scavenger receptors and mRNA of long life gene SIRT1 and SIRT3.
Results
1. The results from the MMT and FCM tests show the 20um resveratrol could be a proper durg concentration.
2. In comparison with foam cell model,it shows a significant decrease in the expression of CD36 mRNA in the CR group(P<0.01),also a decrease in the Res durg group(P<0.05),while there is no significant change in the expression of CD36 mRNA in the Res drug control group(P>0.05);When compared with Res durg group,the expression of CD36 mRNA decrease in the CR group(P<0.05).
3. In comparison with foam cell model,the expression of SIRT1mRNA increases in CR group(P<0.05),and the expression of SIRT1 mRNA shows a significant increase in the Res drug group(P<0.01),while there is no significant change in the Res drug control group(P>0.05);When compared with CR group,the expression of SIRT1 mRNA increase in the Res drug group(P<0.05).
4. In comparison with foam cell model,the expression of SIRT3 mRNA increases in the CR group(P<0.05),however there is no much change in the expression of SIRT3 mRNA in Res drug group(P>0.05),also there is no significant change in the Res drug control group(P>0.05);When compared with CR group, the expression of SIRT3 mRNA decreses in the Res drug group(P<0.05).
Conclusion
1. The expression of mRNA of long life genes of SIRT1 and SIRT3 in U937 foam cell can be up-regulated and the level of mRNA of CD36 of scavenger receptors can be down-regulated by calorie restriction, which has an inhibitary effect on the propagation of foam cell.
2. Resveratrol can up regulate the expression of SIRT1 mRNA in of long life gene,but has no effect on the expression of SIRT3 mRNA,meanwhile through the up-regulation of expression of SIRT1 to reduce the expression of CD36 mRNA of scavenger receptors in U937 foam cell.
3. CR and resveratrol have different regulation on the family of Sir2, what’s more the resveratrol has less inhibitary effect on CD36 in foma cell compared with CR,there might be some other passways except the SIRT1 inhibit the CD36 by CR.
动脉粥样硬化性疾病已经成为威胁人类健康的主要疾病,单核巨噬细胞源性的泡沫细胞是粥样斑块早期形成阶段的典型病变,贯穿于动脉粥样硬化疾病的发生发展。单核细胞源性泡沫细胞上的清道夫受体CD36能识别、内吞氧化型低密度脂蛋白,而氧化型低密度脂蛋白又通过诱导CD36的高表达来刺激其对本身的摄取,形成正反馈,造成胆固醇在细胞内不断积累,最终导致泡沫细胞的形成。泡沫细胞形成后,CD36高表达能诱导单核巨噬细胞向粥样斑块粘附聚集,并参与血管壁的炎症反应,引起动脉粥样硬化的进一步发展。能量限制和白藜芦醇在许多实验中已证实有一定的抗动脉粥样硬化作用,而且研究证实它们均能调节沉默信息调节因子2(Sir2)的表达,我们希望以建立单核巨噬细胞源性泡沫细胞模型为研究的切入点,初步探讨能量限制和白藜芦醇在调节泡沫细胞CD36方面的作用及有关机制。
目的
初步探讨能量限制(calorie restriction,CR)对于单核巨噬细胞源性泡沫细胞清道夫受体CD36的抑制效果及调控通路以及白藜芦醇(resveratrol,Res)是否能完全模拟出CR效果及其原因所在,进行对比实验观察CR与Res对于人U937泡沫细胞CD36和长寿基因SIRT1与SIRT3 mRNA表达的影响。
方法
1.当人U937细胞长至1.0×10~6个/ml后,用终浓度为100ng/ml的佛波酯(phorbol 12-myristate 13-acetate,PMA)和终浓度为80μg/ml的人氧化型低密度脂蛋白(ox-LDL)刺激48h,油红O染色后光镜下可见细胞胞浆内存在大量的脂滴,符合泡沫细胞的形态特征,U937泡沫细胞模型建立。
2.分别用含不同浓度白藜芦醇的培养基培养细胞密度为1.0×10~6个/ml的U937泡沫细胞24小时,并利用四氮唑蓝检测法(MTT)和流式细胞计数检测法(FCM)确定一个对于细胞损伤较小且效果最好的药物作用浓度。
3.U937泡沫细胞模型建立后,随机分为四组:分别用高糖DMEM(泡沫细胞模型组)、低糖DMEM(CR组)、高糖DMEM加白藜芦醇(Res药物组)、高糖DMEM加白藜芦醇与尼克酰胺(Res药物对照组)四种培养基继续培养泡沫细胞48小时。
4.分别提取各组细胞内mRNA,进行逆转录PCR检测,观察各组间泡沫细胞清道夫受体CD36和长寿基因SIRT1、SIRT3的mRNA表达水平情况。
结果
1.MTT和FCM的检测结果显示,20μM白藜芦醇是一个比较合适的药物作用浓度。
2.与泡沫细胞模型组对比,CR组CD36 mRNA表达显著降低(P<0.01),Res药物组CD36 mRNA表达降低(P<0.05),Res药物对照组CD36 mRNA表达没有显著变化(P﹥0.05);与Res药物组对比,CR组CD36 mRNA表达降低(P<0.05)。
3.与泡沫细胞模型组对比,CR组SIRT1 mRNA表达增加(P<0.05), Res药物组SIRT1 mRNA表达显著增加(P<0.01),Res药物对照组SIRT1 mRNA表达没有显著变化(P﹥0.05);与CR组对比,Res药物组SIRT1 mRNA表达增加(P<0.05)。
4.与泡沫细胞模型组对比,CR组SIRT3 mRNA表达增加(P<0.05),Res药物组SIRT3 mRNA表达没有显著变化(P﹥0.05),Res药物对照组SIRT3 mRNA表达没有显著变化(P﹥0.05);与CR组对比,Res药物组SIRT3 mRNA表达降低(P<0.05)。
结论
1. CR能使U937泡沫细胞长寿基因SIRT1及SIRT3的mRNA表达水平上调,清道夫受体CD36的mRNA表达水平下调,对于泡沫细胞的发展有抑制作用。
2.白藜芦醇能使长寿基因SIRT1 mRNA表达水平上调,但对SIRT3 mRNA的表达水平无显著影响,同时通过上调SIRT1的表达使U937泡沫细胞清道夫受体CD36的mRNA表达水平下调。
3. CR和白藜芦醇对泡沫细胞上Sir2家族成员的调节是不同的,而且白藜芦醇对泡沫细胞上CD36的抑制作用不如CR,CR可能还存在除SIRT1以外的途径抑制CD36。
Background
Atherosclerotic disease has become the major disease threatens human health,the foam cells generating from mononuclear macrophage are the classical modification in the early stage and propagating in the pathology of atherosclerosis. The CD36 of scavenger receptors on the foam cells generating from monocytes can recognize and swallow ox-LDL,on the other hand the ox-LDL can induce the highly expression of CD36 and than stimulate the uptake of itself, forming the positive feedback loop which lead to the accumulation of cholesterol in the cell and result in the formation of foam cell. After the generation of foma cells, the highly expression of CD36 can induce the monocytes adhere to atheromatous plaque and participate in the inflammation process of vescular wall leading to the propagation of atherosclerosis. Several studies have already proved that calorie restriction and resveratrol have the effect of anti-atherosclerosis and regulate the expression of Sir2. We hope to run a reserch based on the model of foam cell generating from mononuclear macrophage, discuss the function and related mechanisms of CR and Res in the regulation of CD36 in foam cells.
Objective
To discuss the inhibitory effect and regulation passways of CR on the CD36 of scavenger receptors in the foam cell generating from monocytes. To find out the possibility and potential mechanism of resveratrol mimic the function of CR. To investigate the influence on the expression of CD36 on human U937 foam cell and mRNA of long life gene SIRT1 and SIRT3.
Methods
1. When the amonut of human U937 cells come to 1.0×106 /ml, using the final concentration of 100ng/ml of the phorbol 12-myristate 13-acetate and the final concentration of 80ug/ml of human ox-LDL stimulate cells for 48 hours,after oil red O staining,a large mount of lipid droplet can be viewed in the cytoplasm,which correspond to the morphological feature of foma cell,so that establishe the model of human U937 foam cell.
2. The U937 foam cells in the density of 1.0×106 /ml are cultured in the different concentration of resveratrol culture medium for 24 hours. To find out the best drug concentration which has less injuryed cell,us the MTT and FCM.
3. After establishing the model of U937 foma cell,using four kinds of culture mediums which are high glucose DMEM、low glucose DMEM、high glucose DMEM combine with resveratrol and high glucose combine with resveratrol and nicotimamide continue to culture cell for another 48 hours. And then randomly divide into four groups:①foam cell model②CR group③Res durg group④Res durg control group.
4. To extract the mRNA from the above groups respectively,detect the reverse transportation PCR and examine the expression level of CD36 on scavenger receptors and mRNA of long life gene SIRT1 and SIRT3.
Results
1. The results from the MMT and FCM tests show the 20um resveratrol could be a proper durg concentration.
2. In comparison with foam cell model,it shows a significant decrease in the expression of CD36 mRNA in the CR group(P<0.01),also a decrease in the Res durg group(P<0.05),while there is no significant change in the expression of CD36 mRNA in the Res drug control group(P>0.05);When compared with Res durg group,the expression of CD36 mRNA decrease in the CR group(P<0.05).
3. In comparison with foam cell model,the expression of SIRT1mRNA increases in CR group(P<0.05),and the expression of SIRT1 mRNA shows a significant increase in the Res drug group(P<0.01),while there is no significant change in the Res drug control group(P>0.05);When compared with CR group,the expression of SIRT1 mRNA increase in the Res drug group(P<0.05).
4. In comparison with foam cell model,the expression of SIRT3 mRNA increases in the CR group(P<0.05),however there is no much change in the expression of SIRT3 mRNA in Res drug group(P>0.05),also there is no significant change in the Res drug control group(P>0.05);When compared with CR group, the expression of SIRT3 mRNA decreses in the Res drug group(P<0.05).
Conclusion
1. The expression of mRNA of long life genes of SIRT1 and SIRT3 in U937 foam cell can be up-regulated and the level of mRNA of CD36 of scavenger receptors can be down-regulated by calorie restriction, which has an inhibitary effect on the propagation of foam cell.
2. Resveratrol can up regulate the expression of SIRT1 mRNA in of long life gene,but has no effect on the expression of SIRT3 mRNA,meanwhile through the up-regulation of expression of SIRT1 to reduce the expression of CD36 mRNA of scavenger receptors in U937 foam cell.
3. CR and resveratrol have different regulation on the family of Sir2, what’s more the resveratrol has less inhibitary effect on CD36 in foma cell compared with CR,there might be some other passways except the SIRT1 inhibit the CD36 by CR.
引文
[1] Collot TS, Martin J, McDermott RC, Poston R, McGregor JL. CD36 and macrophages in atherosclerosis. Cardiovasc Res,2007,75(3):468-477.
[2] Harb D, Bujold K, Febbraio M, Sirois MG, Ong H, Marleau S. The role of the scavenger receptor CD36 in regulating mononuclearphago cyte trafficking to atheroscleroticlesions and vascular in flammation. Cardiovas Res,2009,83(1):42-51.
[3] Park YM, Febbraio M, Silverstein RL. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterialintima. J Clin Invest,2009,119(1):136-145.
[4] Jiang JC, Jaruga E, Repnevskaya MV, Jazwinski SM.An intervention resembling caloric restriction prolongs life span and retards aging in yeast. Faseb J,2000,14 (14):2135-2137.
[5] Kaeberlein M, Powers RW, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science,2005,310(5751):1103-1196.
[6] Lin SJ, Guarente L. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol,2003,15(2):241-246.
[7] Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science,2004,305(5682):390-392.
[8] Chen D, Steele AD, Lindquist S, Guarente L. Increase in activity during calorie restriction requires Sirt1. Science,2005,310(5754):1641.
[9] Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, Gu W, Guarente L. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell,2007,6(6):759-767.
[10] Gomez-Cabrera MC, Zaragoza R, Pallardo FV, Vi?a JR. SIRT1 regulation of insulin-signalling pathways in liver, white adipose tissue and pancreas during fasting or calorie restriction. Trends Endocrinol Metab,2007,18(3):91-92.
[11] Imai SI, Armsrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein SIR2 is an NAD-dependent histone deacetylase. Nature,2000,403:795-800.
[12] Borra MT, Smith BC, and Denu JM. Mechanism of human SIRT1 activation by resveratrol. Biol Chem,2005,280(17):17187–17195.
[13] Giannakou ME and Partridge L. The interaction between FOXO and SIRT1: tipping thebalance towards survival. Trends Cell Biol,2004,14(8):408-412.
[14]罗兰,高政南,程丽静. SIRT1与基因转录.中国生物化学与分子生物学报,2007,2(3): 187-193.
[15] Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics,2005,85(2):258–263.
[16] Jang JH, Surh YJ. Protective effects of resveratrol on hydrogen peroxide-induced poptosis in rat pheochromocytoma (PC12) cells. Mutation Res,2001,496(1-2): 181–190.
[17] Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv,2006,6(1):36-47.
[18] Ferguson LR. Role of plant polyphone’s in genomic stability. Mutal Res,2001,475(1-2):89-111.
[19] Su HC, Hung LM, Chen JK. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab,2006, 290(6):E1339-1346.
[20] Chi TC, Chen WP, Chi TL, Kuo TF, Lee SS, Cheng JT, Su MJ. Phosphatidylinositol-3-kinase is involoved in the antihyperglrycemic effect induced by resveratrol in streptozotocin-induced diabetic rats. Life Sci,2007,80(18):1713-1720.
[21] Barger JL, Kayo T, Pugh TD, Prolla TA, Weindruch R. Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart. Exp Gerontol,2008,43(9):859-866.
[22] Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE,2008,3(6):e2264.
[23] Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell,2006,126(5):941-954.
[24] Tiwari RL, Singh V, Barthwal MK. Macrophages: an elusive yet emerging therapeutic target of atherosclerosis. Med Res Rev,2008,28(4):483-544.
[25] Osterud B, Bjorklid E. Role of monocytes in atherogenesis. Physiol Rev,2003,83 (4):1069-1112.
[26] Nicholson AC, Han J, Febbraio M, Silversterin RL, Hajjar DP. Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis. Ann N Y Acad Sci,2001,947:224-228.
[27] Varady KA, Hellerstein MK. Do calorie restriction or alternate-day fasting regimens modulate adipose tissue physiology in a way that reduces chronic disease risk? Nutr Rev,2008,66(6):333-342.
[28] Fontana L. Calorie restriction and cardiometabolic health. Eur J Cardiovasc Prev Rehabil, 2008,15(1):3-9.
[29] Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in Biosphere 2: alterations in physiologic,hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci,2002,57(6):B211–B224.
[30] Heilbronn L K, Ravussin E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr,2003,78(3):361–369.
[31] Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol,2005,6(4):298-305.
[32] Hisahara S, Chiba S, Matsumoto H, Horio Y. Transcriptional regulation of neuronal genes and its effect on neural functions: NAD-dependent histone deacetylase SIRT1 (Sir2α). J Pharmacol Sci,2005,98(3):200–204.
[33] Kaeberlein M, McVey M and Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev,1999, 13(19):2570-2580.
[34] Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide hosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem,2004, 279(49):50754-50763.
[35] Giannakou ME and Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival. Trends Cell Biol,2004,14(8):408-412.
[36] Scher MB, Vaquero A, Reinberg D. SIRT3 is a nuclear NAD+dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev,2007,21 (8):920–928.
[37] Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol,2007,27 (24):8807–8814.
[38] Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, GrishinNV, White M, Yang XJ, Zhao Y. Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey. Mol Cell 2006,23(4):607–618.
[39] Renaud S, de Lorgeril M. Wine, alcohol, platelaets, and the French paradox for coronary heart disease. Lancet,1992,239(8808):1523-1526.
[40] Lamming DW, Wood JG, Sinclair DA. Small molecule that regulate lifespan: evidence for xenohormesis. Mol Microbiol,2004,53:1003-1009.
[41] Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature,2004,430(7000): 686–689.
[42] Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature,2003,425(6954):191–196.
[43] Yu W, Fu YC, Zhou XH, Chen CJ, Wang X, Lin RB, Wang W. Effects of resveratrol on H2O2-induced apoptosis and expression of SIRTs in H9c2 cells. J Cell Biochem,2009, 107(4):741-747.
[44]李全忠,杨永忠,易光辉,王佐,杨向东. U937泡沫细胞模型的建立.中国动脉硬化杂志,1999, 7(2):152-154.
[45] Nozaki S, Kashiwagi H, Yamashita S, Nakagawa T, Kostner B, Tomiyama Y, Nakata A, Ishigami M, Miyagawa J, Kameda-Takemura K. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects. J Clin Invest,1995, 96(4):1859-1865.
[46] Febbraio M, Abumrad NA, Hajjar DP, Sharma K, Cheng W, Pearce SF, Silverstein RL. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem,1999,274(27):19055-19062.
[47] Handberg A, Lopez-Bermejo A, Bassols J, Vendrell J, Ricart W, Fernandez-Real JM. Circulating soluble CD36 is associated with glucose metabolism and interleukin-6 in glucose-intolerant men. Diab Vasc Dis Res,2009,6(1):15-20.
[48] Teupser D, Mueller MA, Koglin J, Wilfert W, Ernst J, von Scheidt W, Steinbeck G, Seidel D, Thiery J. CD36 mRNA expression is increased in CD14(+) monocytes of patients with coronary heart disease. Clin Exp Pharmacol Physiol,2008,35(5-6):552-556.
[49] Handberg A, Skjelland M, Michelsen AE, Sagen EL, Krohg-S?rensen K, Russell D, Dahl A, Ueland T, Oie E, Aukrust P, Halvorsen B. Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability. Stroke,2008,39(11):3092-3095.
[50] McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM,Lemieux M.The mammalian SIR2 alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol,2003,23(1):38-54.
[51] Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J. Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res,2004,95(10):971-980.
[52] Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. PNAS,2008,105 (38):14447 -14452.
[53] Sundaresan NR, Samant SA, Pillai VB. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol,2008,28(20):6384-6401.
[1] Duo MH, Allis CD. Roles of histone acetyltransferases and deacetylases in gene regulation. BioEssays,1998,20(8):615–626.
[2] Sundaresan NR, Samant SA, Pillai VB. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol,2008,28(20):6384-6401.
[3] Hisahara S, Chiba S, Matsumoto H, Horio Y. Transcriptional Regulation of Neuronal Genes and Its Effect on Neural Functions: NAD-Dependent Histone Deacetylase SIRT1 (Sir2α). J Pharmacological Sci,2005,(98):200–204.
[4]罗兰、高政南、程丽静. SIRT1与基因转录.中国生物化学与分子生物学报, 2007,23(3):187-193.
[5] Scher MB, Vaquero A, Reinberg D. SIRT3 is a nuclear NAD+dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev,2007, 21(8):920–928.
[6] Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics,2005,85(2):258–263.
[7] Hallows WC, Lee S, Denu JM. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci,2006,103(27):10230–10235.
[8] Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. PNAS,2008,105(38):14447-14452.
[9] Shi T, Wang F, Stieren E, Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in Brown adipocytes. J Biol Chem, 2005,280(14):13560–13567.
[10] Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C. Substrates and Regulation Mechanisms for the Human Mitochondrial Sirtuins Sirt3 and Sirt5. J Mol Biol,2008,382(3):790–801.
[11] Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol,2007,27 (24):8807–8814.
[12] Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci,2006,103(27):10224–10229.
[13] Jacobs KM, Pennington JD, Bisht KS, Aykin-Burns N, Kim HS, Mishra M, Sun L, Nguyen P, Ahn BH, Leclerc J, Deng CX, Spitz DR, Gius D. SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression. Int J of Biol Sci,2008,4(5):291-299.
[14] Fujino T, Kondo J, Ishikawa M, Morikawa K, Yamamoto TT. Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem, 2001,276(14):11420–11426.
[15] Yu W, Fu YC, Zhou XH, Chen CJ, Wang X, Lin RB, Wang W. Effects of resveratrol on H2O2-induced apoptosis and expression of SIRTs in H9c2 cells. J Cell Biochem, 2009,107(4):741-747.
[16] Hallows WC, Lee S and Denu JM. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci,2006,103(27):10230–10235.
[17] Borra MT, Smith BC, Denu JM. Mechanism of Human SIRT1 Activation by Resveratrol. J Biol Chem,2005,280(17):17187–17195.
[18] Onyango P, Celic I, McCaffery JM, Boeke JD, Feinberg AP. SIRT3, a human SIR2 homologue, is an NAD+ dependent deacetylase localized to mitochondria. PNAS,2002,99 (21):13653–13658.
[19] Yechoor VK, Patti ME, Ueki K, Laustsen PG, Saccone R, Rauniyar R, Kahn CR. Distinct pathways of insulin-regulated versus diabetesregulated gene expression: An in vivo analysis in MIRKO mice. Proc Natl Acad Sci,2004,101(47):16525–16530.
[20] Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y. Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey. Mol Cell,2006,23(4):607–618.
[2] Harb D, Bujold K, Febbraio M, Sirois MG, Ong H, Marleau S. The role of the scavenger receptor CD36 in regulating mononuclearphago cyte trafficking to atheroscleroticlesions and vascular in flammation. Cardiovas Res,2009,83(1):42-51.
[3] Park YM, Febbraio M, Silverstein RL. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterialintima. J Clin Invest,2009,119(1):136-145.
[4] Jiang JC, Jaruga E, Repnevskaya MV, Jazwinski SM.An intervention resembling caloric restriction prolongs life span and retards aging in yeast. Faseb J,2000,14 (14):2135-2137.
[5] Kaeberlein M, Powers RW, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science,2005,310(5751):1103-1196.
[6] Lin SJ, Guarente L. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol,2003,15(2):241-246.
[7] Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science,2004,305(5682):390-392.
[8] Chen D, Steele AD, Lindquist S, Guarente L. Increase in activity during calorie restriction requires Sirt1. Science,2005,310(5754):1641.
[9] Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, Steele AD, Crowe H, Marmor S, Luo J, Gu W, Guarente L. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell,2007,6(6):759-767.
[10] Gomez-Cabrera MC, Zaragoza R, Pallardo FV, Vi?a JR. SIRT1 regulation of insulin-signalling pathways in liver, white adipose tissue and pancreas during fasting or calorie restriction. Trends Endocrinol Metab,2007,18(3):91-92.
[11] Imai SI, Armsrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein SIR2 is an NAD-dependent histone deacetylase. Nature,2000,403:795-800.
[12] Borra MT, Smith BC, and Denu JM. Mechanism of human SIRT1 activation by resveratrol. Biol Chem,2005,280(17):17187–17195.
[13] Giannakou ME and Partridge L. The interaction between FOXO and SIRT1: tipping thebalance towards survival. Trends Cell Biol,2004,14(8):408-412.
[14]罗兰,高政南,程丽静. SIRT1与基因转录.中国生物化学与分子生物学报,2007,2(3): 187-193.
[15] Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics,2005,85(2):258–263.
[16] Jang JH, Surh YJ. Protective effects of resveratrol on hydrogen peroxide-induced poptosis in rat pheochromocytoma (PC12) cells. Mutation Res,2001,496(1-2): 181–190.
[17] Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv,2006,6(1):36-47.
[18] Ferguson LR. Role of plant polyphone’s in genomic stability. Mutal Res,2001,475(1-2):89-111.
[19] Su HC, Hung LM, Chen JK. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab,2006, 290(6):E1339-1346.
[20] Chi TC, Chen WP, Chi TL, Kuo TF, Lee SS, Cheng JT, Su MJ. Phosphatidylinositol-3-kinase is involoved in the antihyperglrycemic effect induced by resveratrol in streptozotocin-induced diabetic rats. Life Sci,2007,80(18):1713-1720.
[21] Barger JL, Kayo T, Pugh TD, Prolla TA, Weindruch R. Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart. Exp Gerontol,2008,43(9):859-866.
[22] Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE,2008,3(6):e2264.
[23] Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell,2006,126(5):941-954.
[24] Tiwari RL, Singh V, Barthwal MK. Macrophages: an elusive yet emerging therapeutic target of atherosclerosis. Med Res Rev,2008,28(4):483-544.
[25] Osterud B, Bjorklid E. Role of monocytes in atherogenesis. Physiol Rev,2003,83 (4):1069-1112.
[26] Nicholson AC, Han J, Febbraio M, Silversterin RL, Hajjar DP. Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis. Ann N Y Acad Sci,2001,947:224-228.
[27] Varady KA, Hellerstein MK. Do calorie restriction or alternate-day fasting regimens modulate adipose tissue physiology in a way that reduces chronic disease risk? Nutr Rev,2008,66(6):333-342.
[28] Fontana L. Calorie restriction and cardiometabolic health. Eur J Cardiovasc Prev Rehabil, 2008,15(1):3-9.
[29] Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in Biosphere 2: alterations in physiologic,hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci,2002,57(6):B211–B224.
[30] Heilbronn L K, Ravussin E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr,2003,78(3):361–369.
[31] Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol,2005,6(4):298-305.
[32] Hisahara S, Chiba S, Matsumoto H, Horio Y. Transcriptional regulation of neuronal genes and its effect on neural functions: NAD-dependent histone deacetylase SIRT1 (Sir2α). J Pharmacol Sci,2005,98(3):200–204.
[33] Kaeberlein M, McVey M and Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev,1999, 13(19):2570-2580.
[34] Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide hosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem,2004, 279(49):50754-50763.
[35] Giannakou ME and Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival. Trends Cell Biol,2004,14(8):408-412.
[36] Scher MB, Vaquero A, Reinberg D. SIRT3 is a nuclear NAD+dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev,2007,21 (8):920–928.
[37] Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol,2007,27 (24):8807–8814.
[38] Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, GrishinNV, White M, Yang XJ, Zhao Y. Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey. Mol Cell 2006,23(4):607–618.
[39] Renaud S, de Lorgeril M. Wine, alcohol, platelaets, and the French paradox for coronary heart disease. Lancet,1992,239(8808):1523-1526.
[40] Lamming DW, Wood JG, Sinclair DA. Small molecule that regulate lifespan: evidence for xenohormesis. Mol Microbiol,2004,53:1003-1009.
[41] Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature,2004,430(7000): 686–689.
[42] Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature,2003,425(6954):191–196.
[43] Yu W, Fu YC, Zhou XH, Chen CJ, Wang X, Lin RB, Wang W. Effects of resveratrol on H2O2-induced apoptosis and expression of SIRTs in H9c2 cells. J Cell Biochem,2009, 107(4):741-747.
[44]李全忠,杨永忠,易光辉,王佐,杨向东. U937泡沫细胞模型的建立.中国动脉硬化杂志,1999, 7(2):152-154.
[45] Nozaki S, Kashiwagi H, Yamashita S, Nakagawa T, Kostner B, Tomiyama Y, Nakata A, Ishigami M, Miyagawa J, Kameda-Takemura K. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects. J Clin Invest,1995, 96(4):1859-1865.
[46] Febbraio M, Abumrad NA, Hajjar DP, Sharma K, Cheng W, Pearce SF, Silverstein RL. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem,1999,274(27):19055-19062.
[47] Handberg A, Lopez-Bermejo A, Bassols J, Vendrell J, Ricart W, Fernandez-Real JM. Circulating soluble CD36 is associated with glucose metabolism and interleukin-6 in glucose-intolerant men. Diab Vasc Dis Res,2009,6(1):15-20.
[48] Teupser D, Mueller MA, Koglin J, Wilfert W, Ernst J, von Scheidt W, Steinbeck G, Seidel D, Thiery J. CD36 mRNA expression is increased in CD14(+) monocytes of patients with coronary heart disease. Clin Exp Pharmacol Physiol,2008,35(5-6):552-556.
[49] Handberg A, Skjelland M, Michelsen AE, Sagen EL, Krohg-S?rensen K, Russell D, Dahl A, Ueland T, Oie E, Aukrust P, Halvorsen B. Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability. Stroke,2008,39(11):3092-3095.
[50] McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM,Lemieux M.The mammalian SIR2 alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol,2003,23(1):38-54.
[51] Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J. Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res,2004,95(10):971-980.
[52] Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. PNAS,2008,105 (38):14447 -14452.
[53] Sundaresan NR, Samant SA, Pillai VB. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol,2008,28(20):6384-6401.
[1] Duo MH, Allis CD. Roles of histone acetyltransferases and deacetylases in gene regulation. BioEssays,1998,20(8):615–626.
[2] Sundaresan NR, Samant SA, Pillai VB. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol,2008,28(20):6384-6401.
[3] Hisahara S, Chiba S, Matsumoto H, Horio Y. Transcriptional Regulation of Neuronal Genes and Its Effect on Neural Functions: NAD-Dependent Histone Deacetylase SIRT1 (Sir2α). J Pharmacological Sci,2005,(98):200–204.
[4]罗兰、高政南、程丽静. SIRT1与基因转录.中国生物化学与分子生物学报, 2007,23(3):187-193.
[5] Scher MB, Vaquero A, Reinberg D. SIRT3 is a nuclear NAD+dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev,2007, 21(8):920–928.
[6] Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics,2005,85(2):258–263.
[7] Hallows WC, Lee S, Denu JM. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci,2006,103(27):10230–10235.
[8] Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. PNAS,2008,105(38):14447-14452.
[9] Shi T, Wang F, Stieren E, Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in Brown adipocytes. J Biol Chem, 2005,280(14):13560–13567.
[10] Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C. Substrates and Regulation Mechanisms for the Human Mitochondrial Sirtuins Sirt3 and Sirt5. J Mol Biol,2008,382(3):790–801.
[11] Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr, Weissman S, Verdin E, Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol,2007,27 (24):8807–8814.
[12] Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci,2006,103(27):10224–10229.
[13] Jacobs KM, Pennington JD, Bisht KS, Aykin-Burns N, Kim HS, Mishra M, Sun L, Nguyen P, Ahn BH, Leclerc J, Deng CX, Spitz DR, Gius D. SIRT3 interacts with the daf-16 homolog FOXO3a in the Mitochondria, as well as increases FOXO3a Dependent Gene expression. Int J of Biol Sci,2008,4(5):291-299.
[14] Fujino T, Kondo J, Ishikawa M, Morikawa K, Yamamoto TT. Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem, 2001,276(14):11420–11426.
[15] Yu W, Fu YC, Zhou XH, Chen CJ, Wang X, Lin RB, Wang W. Effects of resveratrol on H2O2-induced apoptosis and expression of SIRTs in H9c2 cells. J Cell Biochem, 2009,107(4):741-747.
[16] Hallows WC, Lee S and Denu JM. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci,2006,103(27):10230–10235.
[17] Borra MT, Smith BC, Denu JM. Mechanism of Human SIRT1 Activation by Resveratrol. J Biol Chem,2005,280(17):17187–17195.
[18] Onyango P, Celic I, McCaffery JM, Boeke JD, Feinberg AP. SIRT3, a human SIR2 homologue, is an NAD+ dependent deacetylase localized to mitochondria. PNAS,2002,99 (21):13653–13658.
[19] Yechoor VK, Patti ME, Ueki K, Laustsen PG, Saccone R, Rauniyar R, Kahn CR. Distinct pathways of insulin-regulated versus diabetesregulated gene expression: An in vivo analysis in MIRKO mice. Proc Natl Acad Sci,2004,101(47):16525–16530.
[20] Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y. Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey. Mol Cell,2006,23(4):607–618.
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