Journal of Animal Science and Biotechnology | |
Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs | |
Teresa A Davis1  Agus Suryawan1  | |
[1] United States Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA | |
关键词: Ubiquitin; Swine; Protein synthesis; Protein degradation; Neonate; Muscle; Leucine; Insulin; Autophagy; Amino acids; | |
Others : 803659 DOI : 10.1186/2049-1891-5-8 |
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received in 2013-09-08, accepted in 2014-01-14, 发布年份 2014 | |
【 摘 要 】
Background
The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin and amino acids, especially leucine, modulate skeletal muscle protein synthesis and how this changes with development. In the current study, we identified mechanisms involved in protein degradation regulation. In experiment 1, 6- and 26-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic, 2) euinsulinemic-euglycemic-hyperaminoacidemic, and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h. In experiment 2, 5-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic-euleucinemic, 2) euinsulinemic-euglycemic-hypoaminoacidemic-hyperleucinemic, and 3) euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices of ubiquitin-proteasome, i.e., atrogin-1 (MAFbx) and muscle RING-finger protein-1 (MuRF1) and autophagy-lysosome systems, i.e., unc51-like kinase 1 (UKL1), microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (Lamp-2). For comparison, we measured ribosomal protein S6 (rpS6) and eukaryotic initiation factor 4E (eIF4E) activation, components of translation initiation.
Results
Abundance of atrogin-1, but not MuRF1, was greater in 26- than 6-d-old pigs and was not affected by insulin, amino acids, or leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment. The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased by insulin, amino acids, and leucine. These responses were more profound in younger pigs. Abundance of Lamp-2 was not affected by treatment or development. Abundance of eIF4E, but not rpS6, was higher in 6- than 26-d-old-pigs but unaffected by treatment. Phosphorylation of eIF4E was not affected by treatment, however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and the responses decreased with development.
Conclusions
The rapid growth of neonatal muscle is in part due to the positive balance between the activation of protein synthesis and degradation signaling. Insulin, amino acids, and, particularly, leucine, act as signals to modulate muscle protein synthesis and degradation in neonates.
【 授权许可】
2014 Suryawan and Davis; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Sandri M: Autophagy in skeletal muscle. FEBS Lett 2010, 584:1411-1416.
- [2]Young VR: Regulation of protein synthesis and skeletal muscle growth. J Anim Sci 1974, 38:1054-1070.
- [3]Davis TA, Burrin DG, Fiorotto ML, Nguyen HV: Protein synthesis in skeletal muscle and jejunum is more responsive to feeding in 7-than in 26-day-old pigs. Am J Physiol 1996, 270:E802-E809.
- [4]O’Connor PM, Bush JA, Suryawan A, Nguyen HV, Davis TA: Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs. Am J Physiol Endocrinol Metab 2003, 284:E110-E119.
- [5]Escobar J, Frank JW, Suryawan A, Nguyen HV, Kimball SR, Jefferson LS, Davis TA: Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation. Am J Physiol Endocrinol Metab 2005, 288:E914-E921.
- [6]Proud CG: Regulation of protein synthesis by insulin. Biochem Soc Trans 2006, 34:213-216.
- [7]Proud CG: Amino acids and mTOR signalling in anabolic function. Biochem Soc Trans 2007, 35:1187-1190.
- [8]O’Connor PM, Kimball SR, Suryawan A, Bush JA, Nguyen HV, Jefferson LS, Davis TA: Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs. Am J Physiol Endocrinol Metab 2003, 285:E40-E53.
- [9]Davis TA, Suryawan A, Orellana RA, Fiorotto ML, Burrin DG: Amino acids and insulin are regulators of muscle protein synthesis in neonatal pigs. Animal 2010, 4:1790-1796.
- [10]Hong-Brown LQ, Brown CR, Lang CH: HIV antiretroviral agents inhibit protein synthesis and decrease ribosomal protein S6 and 4EBP1 phosphorylation in C2C12 myocytes. AIDS Res Hum Retroviruses 2005, 21:854-862.
- [11]Welle S, Burgess K, Mehta S: Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice. Am J Physiol Endocrinol Metab 2009, 296:E567-E572.
- [12]Williamson DL, Kimball SR, Jefferson LS: Acute treatment with TNF-alpha attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism. Am J Physiol Endocrinol Metab 2005, 289:E95-E104.
- [13]Vary TC, Jefferson LS, Kimball SR: Role of eIF4E in stimulation of protein synthesis by IGF-I in perfused rat skeletal muscle. Am J Physiol Endocrinol Metab 2000, 278:E58-E64.
- [14]Escobar J, Frank JW, Suryawan A, Nguyen HV, Davis TA: Regulation of cardiac and skeletal muscle protein synthesis by branched-chain amino acids in neonates. Am J Physiol Endocrinol Metab 2006, 290:E612-E621.
- [15]Paul PK, Kumar A: TRAF6 coordinates the activation of autophagy and ubiquitin-proteasome systems in atrophying skeletal muscle. Autophagy 2011, 7:555-556.
- [16]Kadowaki M, Kanazawa T: Amino acids as regulators of proteolysis. J Nutr 2003, 133:2052S-2056S.
- [17]Glass DJ: Molecular mechanisms modulating muscle mass. Trends Mol Med 2003, 9:344-350.
- [18]Bonaldo P, Sandri M: Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech 2013, 6:25-39.
- [19]Neel BA, Lin Y, Pessin JE: Skeletal muscle autophagy: a new metabolic regulator. Trends Endocrinol Metab 2013, 24:635-643.
- [20]Cecconi F, Levine B: The role of autophagy in mammalian development: cell makeover rather than cell death. Dev Cell 2008, 15:344-357.
- [21]Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N: The role of autophagy during the early neonatal starvation period. Nature 2004, 432:1032-1036.
- [22]Zhang S, Li X, Li L, Yan X: Autophagy up-regulation by early weaning in the liver, spleen and skeletal muscle of piglets. Br J Nutr 2011, 106:213-217.
- [23]Crotzer VL, Blum JS: Autophagy and intracellular surveillance: modulating MHC class II antigen presentation with stress. Proc Natl Acad Sci U S A 2005, 102:7779-7780.
- [24]Rajawat YS, Hilioti Z, Bossis I: Aging: central role for autophagy and the lysosomal degradative system. Ageing Res Rev 2009, 8:199-213.
- [25]Bach M, Larance M, James DE, Ramm G: The serine/threonine kinase ULK1 is a target of multiple phosphorylation events. Biochem J 2011, 440:283-291.
- [26]Kim J, Kundu M, Viollet B, Guan KL: AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011, 13:132-141.
- [27]Clemmons DR: Role of IGF-I in skeletal muscle mass maintenance. Trends Endocrinol Metab 2009, 20:349-356.
- [28]Banerjee A, Guttridge DC: Mechanisms for maintaining muscle. Curr Opin Support Palliat Care 2012, 6:451-456.
- [29]Béchet D, Tassa A, Combaret L, Taillandier D, Attaix D: Regulation of skeletal muscle proteolysis by amino acids. J Ren Nutr 2005, 15:18-22.
- [30]Klasing KC, Jarrell VL: Regulation of protein degradation in chick muscle by several hormones and metabolites. Poult Sci 1985, 64:694-699.
- [31]Nicastro H, da Luz CR, Chaves DF, Bechara LR, Voltarelli VA, Rogero MM, Lancha AH Jr: Does branched-chain amino acids supplementation modulate skeletal muscle remodeling through inflammation modulation? Possible mechanisms of action. J Nutr Metab 2012, 2012:136937.
- [32]Suryawan A, Nguyen HV, Almonaci RD, Davis TA: Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway. J Anim Sci Biotechnol 2012, 3:3-12. BioMed Central Full Text
- [33]Suryawan A, Davis TA: The abundance and activation of mTORC1 regulators in skeletal muscle of neonatal pigs are modulated by insulin, amino acids, and age. J Appl Physiol 2010, 109:1448-1454.
- [34]Davis TA, Fiorotto ML, Burrin DG, Reeds PJ, Nguyen HV, Beckett PR, Vann RC, O’Connor PM: Stimulation of protein synthesis by both insulin and amino acids is unique to skeletal muscle in neonatal pigs. Am J Physiol Endocrinol Metab 2002, 282:E880-E890.
- [35]Wilson FA, Suryawan A, Gazzaneo MC, Orellana RA, Nguyen HV, Davis TA: Stimulation of muscle protein synthesis by prolonged parenteral infusion of leucine is dependent on amino acid availability in neonatal pigs. J Nutr 2010, 140:264-270.
- [36]Escobar J, Frank JW, Suryawan A, Nguyen HV, Davis TA: Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle. Am J Physiol Endocrinol Metab 2007, 293:E1615-E1621.
- [37]Kruppa J, Clemens MJ: Differential kinetics of changes in the state of phosphorylation of ribosomal protein S6 and in the rate of protein synthesis in MPC 11 cells during tonicity shifts. EMBO J 1984, 3:95-100.
- [38]Ruvinsky I, Sharon N, Lerer T, Cohen H, Stolovich-Rain M, Nir T, Dor Y, Zisman P, Meyuhas O: Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes Dev 2005, 19:2199-2211.
- [39]Meyuhas O: Physiological roles of ribosomal protein S6: one of its kind. Int Rev Cell Mol Biol 2008, 268:1-37.
- [40]Svitkin YV, Herdy B, Costa-Mattioli M, Gingras AC, Raught B, Sonenberg N: Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation. Mol Cell Biol 2005, 25:10556-10565.
- [41]Mamane Y, Petroulakis E, Martineau Y, Sato TA, Larsson O, Rajasekhar VK, Sonenberg N: Epigenetic activation of a subset of mRNAs by eIF4E explains its effects on cell proliferation. PLoS One 2007, 2:e242.
- [42]Mamane Y, Petroulakis E, Rong L, Yoshida K, Ler LW, Sonenberg N: eIF4E–from translation to transformation. Oncogene 2004, 23:3172-3179.
- [43]Muta D, Makino K, Nakamura H, Yano S, Kudo M, Kuratsu J: Inhibition of eIF4E phosphorylation reduces cell growth and proliferation in primary central nervous system lymphoma cells. J Neurooncol 2011, 101:33-39.
- [44]Bianchini A, Loiarro M, Bielli P, Busà R, Paronetto MP, Loreni F, Geremia R, Sette C: Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells. Carcinogenesis 2008, 29:2279-2288.
- [45]Lecker SH, Solomon V, Mitch WE, Goldberg AL: Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr 1999, 129:227S-237S.
- [46]Foletta VC, White LJ, Larsen AE, Léger B, Russell AP: The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch 2011, 461:325-335.
- [47]Orellana RA, Suryawan A, Wilson FA, Gazzaneo MC, Fiorotto ML, Nguyen HV, Davis TA: Development aggravates the severity of skeletal muscle catabolism induced by endotoxemia in neonatal pigs. Am J Physiol Regul Integr Comp Physiol 2012, 302:R682-R690.
- [48]Frost RA, Nystrom GJ, Jefferson LS, Lang CH: Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle. Am J Physiol Endocrinol Metab 2007, 292:E501-E512.
- [49]Carson JA, Baltgalvis KA: Interleukin-6 as a key regulator of muscle mass during chachexia. Exerc Sport Sci Rev 2010, 38:168-176.
- [50]Yoshida T, Semprun-Prieto L, Sukhanov S, Delafontaine P: IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol 2010, 298:H1565-H1570.
- [51]Mourkioti F, Kratsios P, Luedde T, Song YH, Delafontaine P, Adami R, Parente V, Bottinelli R, Pasparakis M, Rosenthal N: Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. J Clin Invest 2006, 116:2945-2954.
- [52]Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE: IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 2004, 119:285-298.
- [53]Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ: Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001, 294:1704-1708.
- [54]Clavel S, Coldefy AS, Kurkdjian E, Salles J, Margaritis I, Derijard B: Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat Tibialis Anterior muscle. Mech Ageing Dev 2006, 127:794-801.
- [55]Léger B, Derave W, De Bock K, Hespel P, Russell AP: Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Res 2008, 11:163-175B.
- [56]Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL: Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A 2001, 98:14440-14445.
- [57]Larsen AE, Tunstall RJ, Carey KA, Nicholas G, Kambadur R, Crowe TC, Cameron-Smith D: Actions of short-term fasting on human skeletal muscle myogenic and atrogenic gene expression. Ann Nutr Metab 2006, 50:476-481.
- [58]Whitman SA, Wacker MJ, Richmond SR, Godard MP: Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal muscle wasting with age. Pflugers Arch 2005, 450:437-446.
- [59]Medina R, Wing SS, Goldberg AL: Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. Biochem J 1995, 307:631-637.
- [60]Kee AJ, Combaret L, Tilignac T, Souweine B, Aurousseau E, Dalle M, Taillandier D, Attaix D: Ubiquitin-proteasome-dependent muscle proteolysis responds slowly to insulin release and refeeding in starved rats. J Physiol 2003, 546:765-776.
- [61]Wauson EM, Zaganjor E, Cobb MH: Amino acid regulation of autophagy through the GPCR TAS1R1-TAS1R3. Autophagy 2013, 9:418-419.
- [62]Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y: In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 2004, 15:1101-1111.
- [63]Mizushima N, Levine B: Autophagy in mammalian development and differentiation. Nat Cell Biol 2010, 12:823-830.
- [64]Davis TA, Fiorotto ML, Nguyen HV, Reeds PJ: Protein turnover in skeletal muscle of suckling rats. Am J Physiol 1989, 257:R1141-R1146.
- [65]Eskelinen EL: Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med 2006, 27:495-502.
- [66]Suryawan A, Orellana RA, Nguyen HV, Jeyapalan AS, Fleming JR, Davis TA: Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated. Am J Physiol Endocrinol Metab 2007, 293:E1597-E1605.