综述 Review

哺乳动物雷帕霉素靶蛋白对仔猪蛋白质沉积的调控

  • 张柏林 ,
  • 张林 ,
  • 于长宁 ,
  • 林猛 ,
  • 高峰 ,
  • 周光宏
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  • 南京农业大学动物科技学院, 江苏省动物源食品生产与安全保障重点实验室, 南京 210095

收稿日期: 2013-05-13

  网络出版日期: 2013-10-27

基金资助

"973"国家重点基础研究计划课题(2013CB127306);中央高校科研基本业务费主创新项目(KYZ201222);江苏省农业三新工程项目

Regulation of Protein Deposition by Mammalian Target of Rapamycin in Piglets

  • ZHANG Bolin ,
  • ZHANG Lin ,
  • YU Changning ,
  • LIN Meng ,
  • GAO Feng ,
  • ZHOU Guanghong
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  • College of Animal Science and Technology, Nanjing Agricultural University, Key Laboratory of Animal Origin Food Production and Safety Guarantee in Jiangsu Province, Nanjing 210095, China

Received date: 2013-05-13

  Online published: 2013-10-27

摘要

哺乳动物雷帕霉素靶蛋白(mTOR)是存在于胞浆中的一种非典型丝氨酸/苏氨酸蛋白激酶,是mRNA翻译的主要调控因子,在感受营养信号、调节细胞增殖与生长中起着关键作用。mTOR复合物1(mTORC1)属于雷帕霉素敏感型,介导动物采食后蛋白质合成的增加,并通过调节真核起始因子4E结合蛋白1(4E-BP1)和核糖体蛋白S6激酶1(S6K1)活性而调控蛋白质的基因转录起始。本文综述了mTOR调控蛋白质沉积机制及其影响因素,为进一步研究mTOR对仔猪蛋白质沉积的调控提供依据。

本文引用格式

张柏林 , 张林 , 于长宁 , 林猛 , 高峰 , 周光宏 . 哺乳动物雷帕霉素靶蛋白对仔猪蛋白质沉积的调控[J]. 动物营养学报, 2013 , 25(11) : 2509 -2514 . DOI: 10.3969/j.issn.1006-267x.2013.11.001

Abstract

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase in cytoplasm and a central regulator of mRNA translation that plays a critical role in sensing the signals of nutrients and regulating cell growth and proliferation. mTOR complex 1 (mTORC1) is more sensitive to rapamycin, which mediates the postprandial increase in muscle protein synthesis. Besides, it regulates the accumulation of protein by enhancing the activity of eukaryotic initiation factor 4E binding protein-1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) to promote translation initiation. This paper reviewed the regulation mechanisms of protein deposition by mTOR and its influencing factors, and provided certain references for further investigation on the regulation of mTOR in protein deposition of piglets.

参考文献

[1] HAY N,SONENBERG N.Upstream and downstream of mTOR[J].Genes & Development,2004,18(16):1926-1945.  

[2] 王蕾,刘坚,侯永清,等.α-酮戊二酸对LPS慢性应激仔猪小肠黏膜形态与功能的影响[J].畜牧兽医学报,2010, 41(1):46-52.

[3] LIEBERTHAL W,LEVINE J S.Mammalian target of rapamycin and the kidney.Ⅰ.The signaling pathway[J].American Journal of Physiology:Renal Physiology,2012,303(1):F1-F10.

[4] YANG X,YANG C,FARBERMAN A,et al.The mammalian target of rapamycin-signaling pathway in regulating metabolism and growth[J].Journal of Animal Science,2008,86(Suppl. 14):E36-E50.

[5] SURYAWAN A,JEYAPALAN A S,ORELLANA R A,et al.Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation[J].American Journal of Physiology:Endocrinology and Metabolism,2008,295(4):E868-E875.

[6] DAVIS T A,FIOROTTO M L,BURRIN D G,et al.Stimulation of protein synthesis by both insulin and amino acids is unique to skeletal muscle in neonatal pigs[J].American Journal of Physiology:Endocrinology and Metabolism,2002,282(4):E880-E890.

[7] O'CONNOR P M,BUSH J A,SURYAWAN A,et al.Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs[J].American Journal of Physiology:Endocrinology and Metabolism,2003,284(1):E110-E119.

[8] SURYAWAN A,ORELLANA R A,NGUYEN H V,et al.Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated[J].American Journal of Physiology:Endocrinology and Metabolism,2007,293(6):E1597-E1605.

[9] INOKI K,LI Y,ZHU T Q,et al.TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling[J].Nature Cell Biology,2002,4(9):648-657.  

[10] KIM E.Mechanisms of amino acid sensing in mTOR signaling pathway[J].Nutrition Research and Practice,2009,3(1):64-71.  

[11] TEE A R,FINGAR D C,MANNING B D,et al.Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling[J].Proceedings of the National Academy of Sciences of the United States of America,2002,99(21):13571-13576.  

[12] GINGRAS A C,RAUGHT B,SONENBERG N.eIF4 initiation factors:effectors of mRNA recruitment to ribosomes and regulators of translation[J].Annual Review of Biochemistry,1999,68:913-963.

[13] FUMAGALLI S,THOMAS G.S6 phosphorylation and signal transduction[M]//SONENBERG N,HERSHEY J W B,MATHEWS M B.Translational control of gene expression.New York:Cold Spring Harbor Laboratory Press,2000:695-717.

[14] ZONCU R,EFEYAN A,SABATINI D M.mTOR:from growth signal integration to cancer,diabetes and ageing[J].Nature Reviews Molecular Cell Biology,2011,12(1):21-35.  

[15] BLOMMAART E F C,LUIKEN J J F P,BLOMMAART P J E,et al.Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes[J].Journal of Biological Chemistry,1995,270(5):2320-2326.  

[16] HARA K,YONEZAWA K,WENG Q P,et al.Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism[J].Journal of Biological Chemistry,1998,273(23):14484-14494.  

[17] GAO X S,ZHANG Y,ARRAZOLA P,et al.Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling[J].Nature Cell Biology,2002,4(9):699-704.  

[18] HAN J M,JEONG S J,PARK M C,et al.Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway[J].Cell,2012,149(2):410-424.  

[19] SMITH E M,FINN S G,TEE A R,et al.The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses[J].Journal of Biological Chemistry,2005,280(19):18717-18727.  

[20] LONG X M,ORTIZ-VEGA S,LIN Y S,et al.Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency[J].Journal of Biological Chemistry,2005,280(25):23433-23436.  

[21] NOBUKUNI T,JOAQUIN M,ROCCIO M,et al.Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase[J].Proceedings of the National Academy Science of the United States of America,2005,102(40):14238-14243.  

[22] BYFIELD M P,MURRAY J T,BACKER J M.hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase[J].The Journal of Biological Chemistry,2005,280(38):33076-33082.  

[23] 刘效磊,牛燕媚,傅力.mTOR/S6K1信号通路研究进展[J].中国运动医学杂志,2010,29(1):118-121.

[24] DENG D,YAO K,CHU W Y,et al.Impaired translation initiation activation and reduced protein synthesis in weaned piglets fed a low-protein diet[J].The Journal of Nutritional Biochemistry,2009,20(7):544-552.  

[25] FRANK J W,ESCOBAR J,SURYAWAN A,et al.Dietary protein and lactose increase translation initiation factor activation and tissue protein synthesis in neonatal pigs[J].American Journal of Physiology:Endocrinology and Metabolism,2006,290(2):E225-E233.

[26] TORRAZZA R M,SURYAWAN A,GAZZANEO M C,et al.Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation[J].The Journal of Nutrition,2010,140(12):2145-2152.  

[27] 胡琴,李铁军,康萍,等.新生仔猪蛋白质合成的调控机制[J].生命科学,2008,20(1):131-137.

[28] KIMBALL S R,JEFFERSON L S.Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis[J].The Journal of Nutrition,2006,136(1):227S-231S.

[29] WANG X M,PROUD C G.The mTOR pathway in the control of protein synthesis[J].Physiology,2006,21:362-369.

[30] ESCOBAR J,FRANK J W,SURYAWAN A,et al.Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle[J].American Journal of Physiology:Endocrinology and Metabolism,2007,293(6):E1615-E1621.

[31] RHOADS J M,CORL B A,HARRELL R,et al.Intestinal ribosomal p70 (S6K) signaling is increased in piglet rotavirus enteritis[J].American Journal of Physiology:Gastrointestinal and Liver Physiology,2007,292(3):G913-G922.

[32] YAO K,YIN Y L,CHU W,et al.Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs[J].The Journal of Nutrition,2008,138(5):867-872.

[33] XI P B,JIANG Z Y,DAI Z L,et al.Regulation of protein turnover by L-glutamine in porcine intestinal epithelial cells[J].The Journal of Nutritional Biochemistry,2012,23(8):1012-1017.  

[34] KIMBALL S R,JEFFERSON L S.Regulation of protein synthesis by branched-chain amino acids[J].Current Opinion in Clinical Nutrition and Metabolic Care,2001,4(1):39-43.  

[35] DAVIS T A,FIOROTTO M L,BURRIN D G,et al.Intrauterine growth restriction does not alter response of protein synthesis to feeding in newborn pigs[J].The American Journal of Physiology,1997,272(5):E877-E884.

[36] O'CONNOR P M,KIMBALL S R,SURYAWAN A,et al.Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs[J].American Journal of Physiology:Endocrinology Metabolism,2003,285(1):E40-E53.

[37] DAVIS T A,BURRIN D G,FIOROTTO M L,et al.Protein synthesis in skeletal muscle and jejunum is more responsive to feeding in 7-than in 26-day-old pigs[J].The American Journal of Physiology,1996,270(5 Pt 1):E802-E809.

[38] SURYAWAN A,ORELLANA R A,NGUYEN H V,et al.Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated[J].American Journal of Physiology:Endocrinology and Metabolism,2007,293(6):E1597-E1605.

[39] WILSON F A,SURYAWAN A,ORELLANA R A,et al.Feeding rapidly stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing translation initiation[J].The Journal of Nutrition,2009,139(10):1873-1880.  

[40] GAZZANEO M C,ORELLANA R A,SURYAWAN A,et al.Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal[J].Pediatric Research,2011,70(3):253-260.  
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