奶牛乳腺主要乳成分合成代谢的转录组学研究
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摘要
乳腺是哺乳动物特有的器官,乳腺的功能是泌乳。哺乳动物乳腺经历了形态和结构上-系列的变化,这些变化与乳腺的物质代谢密切相关,乳腺物质代谢直接影响乳的质量和产量。目前尚缺乏对乳腺物质代谢的系统研究。
本实验以荷斯坦奶牛为实验材料,采用荧光定量PCR技术检测αs1-casein、αs2-casein、 β-casein、κ-casein、β-lactoglobin、WAP基因在乳腺发育各时期的表达,结果显示,这些蛋白质基因在泌乳期表达均上调。PCR技术检测与乳腺蛋白质转录和翻译作用相关的PRLR、 AKT1、STAT5、 ELF5、EIF4EBP1、S6K基因表达,结果显示,EIF4EBP1的基因表达下调,其它基因表达上调,并且与乳蛋白质基因表达趋势基本一致,提示EIF4EBP1对泌乳具有抑制作用,其它基因在转录或翻译水平调控乳蛋白质的合成。PRLR通过JAK2激活STAT5在转录水平发挥作用,AKT1则通过mTOR对EIF4EBP1的负调控和对S6K的正调控在翻译水平发挥作用。采用HPLC方法检测乳腺中β-酪蛋白,最早出现在妊娠6个月。
采用荧光定量PCR技术检测乳腺发育各时期一系列乳脂合成相关基因,脂肪酸摄入(VLDLR、LPL)、外源胆固醇运输(ABCA1、ABCG2)、细胞内脂肪酸运输(FABP3、ACBP)、长链(ACSL1)和短链脂肪酸(ACSS2、ACSS1)的活化、脂肪酸从头合成(ACACA、FAS)、去饱和(SCD、FADS1、FADS2)、三酰基甘油合成(AGPAT6、GPAM、LPIN、DGAT1、DGAT2)、脂质小滴形成(BTN1A1、XDH、ADFP)(?)口转录调节(PPARG、SREBF1、SREBF2)等基因的表达,结果显示这些基因在泌乳期表达上调。SREBP1、SREBP2和PPARG对乳脂合成相关的许多基因表达具有调控作用,PRLR、AKT1对奶牛乳腺脂代谢的调控主要是通过PRLR、AKT1对SREBP1的调控来实现。采用气相色谱方法检测乳中脂肪酸组成及含量,荷斯坦奶牛乳脂肪酸中C18：1含量最高,其次为C16：0、C18：0。
采用荧光定量PCR技术检测乳腺发育各时期GLUT1、HKⅠ、HKⅡ、LALBA、β-1,4-半乳糖基转移酶基因的表达,结果表明,这些基因在泌乳期表达上调,表明奶牛乳腺组织在泌乳期合成大量的乳糖。乳糖主要由β-1,4-半乳糖基转移酶和LALBA催化合成。采用HPLC方法检测乳腺乳糖含量,直到妊娠6月乳腺开始出现乳糖。采用Western blotting (?)(?)免疫荧光法对奶牛乳腺发育各时期GLUT1蛋白水平表达及GLUT1蛋白定位进行检测,结果表明：在乳腺发育各时期,GLUT1蛋白水平和GLUT1mRNA水平表达趋势相似。青春期,乳腺中GLUT1mRNA和蛋白的表达量较低；妊娠期开始升高,整个泌乳期持续高表达,泌乳140日达到峰值,此后开始下降。进入退化期,乳腺上皮细胞凋亡,GLUT1蛋白和GLUT1mRNA表达显著下降。青春期和妊娠早期,GLUT1主要定位在乳腺导管上皮细胞；妊娠晚期和泌乳期,GLUT1主要定位在乳腺上皮细胞基底侧细胞膜和顶膜；这些研究结果表明,奶牛乳腺主要通过GLUT1吸收葡萄糖为乳腺发育和泌乳提供能量和底物。
Mammary gland is a unique organ in mammals. Its function is lactation. Mammary gland undergoes a series of changes in morphology and structure.These changes are closely related to material metabolism in mammary gland which directly affect the quality and product of milk. There are very a few substance metabolism studies on the development of mammalian mammary gland in different period, especially dairy cow.
Genes of four caseins and two whey proteins were detected by using fluorescent quantitative RT-PCR in different developmental periods of mammary gland. The results showed that all genes were up-regulated in lactation period. The expression of PRLR, AKT1, STAT5, ELF5, EIF4BP1、 S6K which may relate to protein metabolism in mammary gland were detected, the results showed that other genes had the same expression tendency with milk proteins genes expect EIF4EBP1. It implied that they involved in processes of transcription or translation of milk proteins. Down-regulation of EIF4EBP1demonstrated its negative roles in lactation. PRLR regulated the transcription of milk proteins by the activation of STAT5from JAK2. AKT1played important roles at the level of translation of milk proteins through the negative regulation of mTOR on EIF4EBP1and positive regulation of mTOR on S6K.β-casein was first appeared at6month in pregnancy in cow mammary gland.
Some genes were chosen from different aspects in lipid metabolism to detect their mRNA levels by fluorescent quantitative RT-PCR. They included:VLDLR, LPL which related to the uptake of fatty acid. FABP3, ACBP which related to the transport of fatty acid in cell.ABCA1, ABCG2which related to the transport of foreign cholesterol. Activation of ACSL1, ACSS2, ACSS1. ACACA, FAS which related to the fatty acid de novo synthesis. SCD, FADS1, FADS2which related to desaturation. AGPAT6, GPAM, LPIN, DGAT1, DGAT2which related to the synthesis of triacylglycerol. BTNlA1, XDH, ADFP which related to the synthesis of lipid droplet. PPARG, SREBF1and SREBF2which related to transcriptional regulation. The results showed that these genes expressed in mammary gland epithelium appeared up-regulated in lactation period. SREBP1and SREBP2and PPARG were located in the centre of the lipid metabolism regulation.The Regulation of PRLR、AKT1to lipid metabolism in diary cow mammary gland was realized through regulation of SREBP1.C16:0, C18:0and C18:1contents were higher than the other fatty acids in cow milk.
Technology of fluorescent quantitative RT-PCR was used to detect the mRNA expression of HK Ⅰ, HKⅡ, GLUT1, LALBA and β-1,4-galactosyl transferase in different period of dairy cow mammary gland. The results showed that mRNA expression of these genes were increased and large of lactose was synthesized in mammary gland of cows during the whole lactation. LALBA and β-1,4-galactosyl transferase were the key enzyme that catalysis lactose. HPLC was chosen to detect the lactose in mamary gland to determine the time point of lactose synthesis and its production. Lactose appeared until6month in pregnancy in mammary gland.The expression and the localization of glucose transporter-1(GLUT1) were detected in different period of dairy cow mammary gland by Western blotting and laser scanning confocal microscopy. The results showed that the expression of GLUT1protein are similar to the expression of GLUT1mRNA in different period of dairy cow mammary gland. In virgin, the expression of GLUT1mRNA and GLUT1protein was lowest and increased during pregnancy. On140day of lactation, the expression of GLUT1mRNA and GLUT1protein reached the highest levels and remained high levels during the whole lactation. In involution, the expression of GLUT1mRNA and GLUT1protein was decresaed because of apoptosis of mammary epithelial cells. In virgin and early pregnancy, GLUT1was found in ductal epithelial cells; in late pregnancy and lactation, GLUT1was detected in alveolus epithelial cells near to the basal lamina and epiphragm.These results showed that GLUT1could taransfer extracellular glucose into cells to provide enerage and substance for mammary gland development and lactation.
本实验以荷斯坦奶牛为实验材料,采用荧光定量PCR技术检测αs1-casein、αs2-casein、 β-casein、κ-casein、β-lactoglobin、WAP基因在乳腺发育各时期的表达,结果显示,这些蛋白质基因在泌乳期表达均上调。PCR技术检测与乳腺蛋白质转录和翻译作用相关的PRLR、 AKT1、STAT5、 ELF5、EIF4EBP1、S6K基因表达,结果显示,EIF4EBP1的基因表达下调,其它基因表达上调,并且与乳蛋白质基因表达趋势基本一致,提示EIF4EBP1对泌乳具有抑制作用,其它基因在转录或翻译水平调控乳蛋白质的合成。PRLR通过JAK2激活STAT5在转录水平发挥作用,AKT1则通过mTOR对EIF4EBP1的负调控和对S6K的正调控在翻译水平发挥作用。采用HPLC方法检测乳腺中β-酪蛋白,最早出现在妊娠6个月。
采用荧光定量PCR技术检测乳腺发育各时期一系列乳脂合成相关基因,脂肪酸摄入(VLDLR、LPL)、外源胆固醇运输(ABCA1、ABCG2)、细胞内脂肪酸运输(FABP3、ACBP)、长链(ACSL1)和短链脂肪酸(ACSS2、ACSS1)的活化、脂肪酸从头合成(ACACA、FAS)、去饱和(SCD、FADS1、FADS2)、三酰基甘油合成(AGPAT6、GPAM、LPIN、DGAT1、DGAT2)、脂质小滴形成(BTN1A1、XDH、ADFP)(?)口转录调节(PPARG、SREBF1、SREBF2)等基因的表达,结果显示这些基因在泌乳期表达上调。SREBP1、SREBP2和PPARG对乳脂合成相关的许多基因表达具有调控作用,PRLR、AKT1对奶牛乳腺脂代谢的调控主要是通过PRLR、AKT1对SREBP1的调控来实现。采用气相色谱方法检测乳中脂肪酸组成及含量,荷斯坦奶牛乳脂肪酸中C18：1含量最高,其次为C16：0、C18：0。
采用荧光定量PCR技术检测乳腺发育各时期GLUT1、HKⅠ、HKⅡ、LALBA、β-1,4-半乳糖基转移酶基因的表达,结果表明,这些基因在泌乳期表达上调,表明奶牛乳腺组织在泌乳期合成大量的乳糖。乳糖主要由β-1,4-半乳糖基转移酶和LALBA催化合成。采用HPLC方法检测乳腺乳糖含量,直到妊娠6月乳腺开始出现乳糖。采用Western blotting (?)(?)免疫荧光法对奶牛乳腺发育各时期GLUT1蛋白水平表达及GLUT1蛋白定位进行检测,结果表明：在乳腺发育各时期,GLUT1蛋白水平和GLUT1mRNA水平表达趋势相似。青春期,乳腺中GLUT1mRNA和蛋白的表达量较低；妊娠期开始升高,整个泌乳期持续高表达,泌乳140日达到峰值,此后开始下降。进入退化期,乳腺上皮细胞凋亡,GLUT1蛋白和GLUT1mRNA表达显著下降。青春期和妊娠早期,GLUT1主要定位在乳腺导管上皮细胞；妊娠晚期和泌乳期,GLUT1主要定位在乳腺上皮细胞基底侧细胞膜和顶膜；这些研究结果表明,奶牛乳腺主要通过GLUT1吸收葡萄糖为乳腺发育和泌乳提供能量和底物。
Mammary gland is a unique organ in mammals. Its function is lactation. Mammary gland undergoes a series of changes in morphology and structure.These changes are closely related to material metabolism in mammary gland which directly affect the quality and product of milk. There are very a few substance metabolism studies on the development of mammalian mammary gland in different period, especially dairy cow.
Genes of four caseins and two whey proteins were detected by using fluorescent quantitative RT-PCR in different developmental periods of mammary gland. The results showed that all genes were up-regulated in lactation period. The expression of PRLR, AKT1, STAT5, ELF5, EIF4BP1、 S6K which may relate to protein metabolism in mammary gland were detected, the results showed that other genes had the same expression tendency with milk proteins genes expect EIF4EBP1. It implied that they involved in processes of transcription or translation of milk proteins. Down-regulation of EIF4EBP1demonstrated its negative roles in lactation. PRLR regulated the transcription of milk proteins by the activation of STAT5from JAK2. AKT1played important roles at the level of translation of milk proteins through the negative regulation of mTOR on EIF4EBP1and positive regulation of mTOR on S6K.β-casein was first appeared at6month in pregnancy in cow mammary gland.
Some genes were chosen from different aspects in lipid metabolism to detect their mRNA levels by fluorescent quantitative RT-PCR. They included:VLDLR, LPL which related to the uptake of fatty acid. FABP3, ACBP which related to the transport of fatty acid in cell.ABCA1, ABCG2which related to the transport of foreign cholesterol. Activation of ACSL1, ACSS2, ACSS1. ACACA, FAS which related to the fatty acid de novo synthesis. SCD, FADS1, FADS2which related to desaturation. AGPAT6, GPAM, LPIN, DGAT1, DGAT2which related to the synthesis of triacylglycerol. BTNlA1, XDH, ADFP which related to the synthesis of lipid droplet. PPARG, SREBF1and SREBF2which related to transcriptional regulation. The results showed that these genes expressed in mammary gland epithelium appeared up-regulated in lactation period. SREBP1and SREBP2and PPARG were located in the centre of the lipid metabolism regulation.The Regulation of PRLR、AKT1to lipid metabolism in diary cow mammary gland was realized through regulation of SREBP1.C16:0, C18:0and C18:1contents were higher than the other fatty acids in cow milk.
Technology of fluorescent quantitative RT-PCR was used to detect the mRNA expression of HK Ⅰ, HKⅡ, GLUT1, LALBA and β-1,4-galactosyl transferase in different period of dairy cow mammary gland. The results showed that mRNA expression of these genes were increased and large of lactose was synthesized in mammary gland of cows during the whole lactation. LALBA and β-1,4-galactosyl transferase were the key enzyme that catalysis lactose. HPLC was chosen to detect the lactose in mamary gland to determine the time point of lactose synthesis and its production. Lactose appeared until6month in pregnancy in mammary gland.The expression and the localization of glucose transporter-1(GLUT1) were detected in different period of dairy cow mammary gland by Western blotting and laser scanning confocal microscopy. The results showed that the expression of GLUT1protein are similar to the expression of GLUT1mRNA in different period of dairy cow mammary gland. In virgin, the expression of GLUT1mRNA and GLUT1protein was lowest and increased during pregnancy. On140day of lactation, the expression of GLUT1mRNA and GLUT1protein reached the highest levels and remained high levels during the whole lactation. In involution, the expression of GLUT1mRNA and GLUT1protein was decresaed because of apoptosis of mammary epithelial cells. In virgin and early pregnancy, GLUT1was found in ductal epithelial cells; in late pregnancy and lactation, GLUT1was detected in alveolus epithelial cells near to the basal lamina and epiphragm.These results showed that GLUT1could taransfer extracellular glucose into cells to provide enerage and substance for mammary gland development and lactation.
引文
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