リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Studies on the role of leucine and mTOR signaling in skeletal muscle physiology」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Studies on the role of leucine and mTOR signaling in skeletal muscle physiology

Sato, Yoriko 東京農工大学

2022.05.18

概要

Skeletal muscle is the largest metabolic organ, consuming about 20 % of the body daily expenditure of energy. Although the main function of skeletal muscle is “contraction” to move body and provide stability, it also works as a protein storage, serving as a source of amino acids to be utilized for energy production during food deprivation. Skeletal muscle tissue is composed by two basic types of fibers (slow and fast) with different metabolic, morphologic and contractile characteristics. Since slow twitch fiber (type I fiber) have a high oxidative capacity and prefer fatty acids as substrate, and are resistant to fatigue, it should be benefit to control muscle fiber type by exercise, drugs and nutrients.

Amino acids are taken in supplement form for a natural way to boost athletic performance or improve health since they play many critical roles in the body. Among these supplemental amino acids, branched chain amino acids (BCAAs), are utilize as an energy for skeletal muscle. Among the BCAAs, leucine is well known to regulate protein metabolism through the activation of mechanistic target of rapamycin (mTOR) signaling. Also, previous reports have demonstrated that mTOR signaling is involved in various cellular events, such as regulation of muscle fiber-type, fiber size, mitochondrial biogenesis and differentiation in skeletal muscle.

However, the role of leucine and mTOR signaling in skeletal muscle physiology has not been fully examined. Thus, in this doctoral thesis, to investigate the effects of leucine and mTOR signaling in skeletal muscle physiology including, fiber-type, myogenic differentiation and metabolic alteration, following studies were performed.

In chapter 2, it was investigated whether the acute oral administration of leucine affect muscle fiber-type and mitochondrial biogenesis in skeletal muscle of rats. Although the gene expression of representative glycolytic enzymes (Hk2 and Eno3) were not altered, leucine administration (135 mg/100 g B.W.) up-regulated the expression of slow-fiber related genes (Myh7, Myl3 and Tnni1) and a mitochondrial biogenesis related gene (Ppargc1a) in the soleus and extensor digitorum longus (EDL) muscles compared with the control. In addition, leucine treatment also up-regulated the slow-fiber genes and mitochondrial gene expression in cultured C2C12 myotubes, while rapamycin inhibited the effects of leucine. The hypothesis was accepted that acute administration of leucine alone can up-regulate mitochondrial genes and slow-fiber related gene expression through mTOR signaling. The results suggested the possibility that leucine can alter fiber-type muscle cells and regulate metabolism in skeletal muscle.

In chapter 3, it was examined whether leucyl-tRNA synthetase (Lars), an intracellular sensor for leucine, is involved in the regulation of mTOR signaling and skeletal muscle physiology including, myogenic differentiation, hypertrophy and energy metabolism. By using small interfering (si)-RNA, it was shown that knockdown of Lars decreased phosphorylated p70 S6 kinase, a crucial downstream target of mTOR signaling, in C2C12 mouse myoblasts. Lars knockdown inhibited the differentiation of C2C12 myoblasts into myotubes, and this was accompanied with decreased level of Insulin-like growth factor 2 (Igf2) mRNA expression from the early stages of differentiation. The results suggested the possibility of an association between the mTOR–IGF2 axis and Lars in myogenic differentiation. However, Lars knockdown did not affect the hypertrophy of myotubes and energy metabolism (glycolysis and mitochondrial respiration) of myotubes. The results demonstrated for the first time that Lars is essential for the activation of mTOR signaling in skeletal muscle cells and myogenic differentiation through the induction of Igf2 expression.

In chapter 4, the role of catabolism of BCAAs in C2C12 myoblasts were investigated. The catabolism of BCAAs is mediated by branched chain aminotransferase 2 (BCAT2) and branched chain alpha keto acid dehydrogenase (BCKDH) in mitochondria of skeletal muscle. Although BCAAs metabolism is basically assumed to be carried out in differentiated myofibers, it remains unclear whether BCAAs metabolic enzymes are expressed in undifferentiated myoblasts, and the physiological significance of BCAAs metabolism in myoblasts. Since the expression of BCAAs metabolic enzymes (Bcat2, Bckdha and Bckdk) were confirmed in both undifferentiated myoblasts and differentiated myotubes by qRT-PCR, the catabolism of BCAAs were promoted by the BCKDK inhibitor BT2 in C2C12 myoblasts. The activation of BCAAs catabolism by BT2 impaired C2C12 myoblasts proliferation and differentiation. The results suggested the possibility that increased BCAAs catabolism inhibits myoblasts proliferation and differentiation.

The findings should be important in the fields of nutrition, skeletal muscle physiology and metabolic disease, and contributes to the development of novel functional foods and supplements.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

[1] I. Janssen, S.B. Heymsfield, Z.M. Wang, R. Ross, Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr, J Appl Physiol (1985) 89 (2000) 81-88. 10.1152/jappl.2000.89.1.81.

[2] J.M. Argiles, N. Campos, J.M. Lopez-Pedrosa, R. Rueda, L. Rodriguez-Manas, Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease, J Am Med Dir Assoc 17 (2016) 789-796. 10.1016/j.jamda.2016.04.019.

[3] M. Hargreaves, L.L. Spriet, Skeletal muscle energy metabolism during exercise, Nat Metab (2020). 10.1038/s42255-020-0251-4.

[4] S. Schiaffino, A.C. Rossi, V. Smerdu, L.A. Leinwand, C. Reggiani, Developmental myosins: expression patterns and functional significance, Skelet Muscle 5 (2015) 22. 10.1186/s13395-015- 0046-6.

[5] D. Pette, R.S. Staron, Myosin isoforms, muscle fiber types, and transitions, Microsc Res Tech 50 (2000) 500-509. 10.1002/1097-0029(20000915)50:6<500::AID-JEMT7>3.0.CO;2-7.

[6] W. Scott, J. Stevens, S.A. Binder-Macleod, Human skeletal muscle fiber type classifications, Phys Ther 81 (2001) 1810-1816.

[7] S. Schiaffino, C. Reggiani, Fiber types in mammalian skeletal muscles, Physiol Rev 91 (2011) 1447-1531. 10.1152/physrev.00031.2010.

[8] R.A. DeFronzo, D. Tripathy, Skeletal muscle insulin resistance is the primary defect in type 2 diabetes, Diabetes Care 32 Suppl 2 (2009) S157-163. 10.2337/dc09-S302.

[9] B.B. Rasmussen, R.R. Wolfe, Regulation of fatty acid oxidation in skeletal muscle, Annu Rev Nutr 19 (1999) 463-484. 10.1146/annurev.nutr.19.1.463.

[10] K.K. Baskin, B.R. Winders, E.N. Olson, Muscle as a "mediator" of systemic metabolism, Cell Metab 21 (2015) 237-248. 10.1016/j.cmet.2014.12.021.

[11] H. Wu, B. Rothermel, S. Kanatous, P. Rosenberg, F.J. Naya, J.M. Shelton, K.A. Hutcheson, J.M. DiMaio, E.N. Olson, R. Bassel-Duby, R.S. Williams, Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway, EMBO J 20 (2001) 6414-6423. 10.1093/emboj/20.22.6414.

[12] M. Schuler, F. Ali, C. Chambon, D. Duteil, J.M. Bornert, A. Tardivel, B. Desvergne, W. Wahli, P. Chambon, D. Metzger, PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes, Cell Metab 4 (2006) 407-414. 10.1016/j.cmet.2006.10.003.

[13] H. Liang, W.F. Ward, PGC-1alpha: a key regulator of energy metabolism, Adv Physiol Educ 30 (2006) 145-151. 10.1152/advan.00052.2006.

[14] M.P. Czubryt, J. McAnally, G.I. Fishman, E.N. Olson, Regulation of peroxisome proliferator- activated receptor gamma coactivator 1 alpha (PGC-1 alpha ) and mitochondrial function by MEF2 and HDAC5, Proc Natl Acad Sci U S A 100 (2003) 1711-1716. 10.1073/pnas.0337639100.

[15] J. Lin, C. Handschin, B.M. Spiegelman, Metabolic control through the PGC-1 family of transcription coactivators, Cell Metab 1 (2005) 361-370. 10.1016/j.cmet.2005.05.004.

[16] J. Lin, H. Wu, P.T. Tarr, C.Y. Zhang, Z. Wu, O. Boss, L.F. Michael, P. Puigserver, E. Isotani, E.N. Olson, B.B. Lowell, R. Bassel-Duby, B.M. Spiegelman, Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres, Nature 418 (2002) 797-801. 10.1038/nature00904.

[17] C. Zechner, L. Lai, J.F. Zechner, T. Geng, Z. Yan, J.W. Rumsey, D. Collia, Z. Chen, D.F. Wozniak, T.C. Leone, D.P. Kelly, Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity, Cell Metab 12 (2010) 633-642. 10.1016/j.cmet.2010.11.008.

[18] J. Talbot, L. Maves, Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease, Wiley Interdiscip Rev Dev Biol 5 (2016) 518-534. 10.1002/wdev.230.

[19] L.D. Brown, Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health, J Endocrinol 221 (2014) R13-29. 10.1530/JOE-13-0567.

[20] D. Zhang, X. Wang, Y. Li, L. Zhao, M. Lu, X. Yao, H. Xia, Y.C. Wang, M.F. Liu, J. Jiang, X. Li, H. Ying, Thyroid hormone regulates muscle fiber type conversion via miR-133a1, J Cell Biol 207 (2014) 753-766. 10.1083/jcb.201406068.

[21] Y.X. Wang, C.L. Zhang, R.T. Yu, H.K. Cho, M.C. Nelson, C.R. Bayuga-Ocampo, J. Ham, H. Kang, R.M. Evans, Regulation of muscle fiber type and running endurance by PPARdelta, PLoS Biol 2 (2004) e294. 10.1371/journal.pbio.0020294.

[22] J.L. Ruas, J.P. White, R.R. Rao, S. Kleiner, K.T. Brannan, B.C. Harrison, N.P. Greene, J. Wu, J.L. Estall, B.A. Irving, I.R. Lanza, K.A. Rasbach, M. Okutsu, K.S. Nair, Z. Yan, L.A. Leinwand, B.M. Spiegelman, A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy, Cell 151 (2012) 1319-1331. 10.1016/j.cell.2012.10.050.

[23] C. Canto, J. Auwerx, PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure, Curr Opin Lipidol 20 (2009) 98-105. 10.1097/MOL.0b013e328328d0a4.

[24] V.A. Narkar, M. Downes, R.T. Yu, E. Embler, Y.X. Wang, E. Banayo, M.M. Mihaylova, M.C. Nelson, Y. Zou, H. Juguilon, H. Kang, R.J. Shaw, R.M. Evans, AMPK and PPARdelta agonists are exercise mimetics, Cell 134 (2008) 405-415. 10.1016/j.cell.2008.06.051.

[25] M.C. Manio, K. Inoue, M. Fujitani, S. Matsumura, T. Fushiki, Combined pharmacological activation of AMPK and PPARdelta potentiates the effects of exercise in trained mice, Physiol Rep 4 (2016). 10.14814/phy2.12625.

[26] M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin, N. Messadeq, J. Milne, P. Lambert, P. Elliott, B. Geny, M. Laakso, P. Puigserver, J. Auwerx, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC- 1alpha, Cell 127 (2006) 1109-1122. 10.1016/j.cell.2006.11.013.

[27] W. Mizunoya, H. Miyahara, S. Okamoto, M. Akahoshi, T. Suzuki, M.K. Do, H. Ohtsubo, Y. Komiya, M. Lan, T. Waga, A. Iwata, K. Nakazato, Y. Ikeuchi, J.E. Anderson, R. Tatsumi, Improvement of Endurance Based on Muscle Fiber-Type Composition by Treatment with Dietary Apple Polyphenols in Rats, PLoS One 10 (2015) e0134303. 10.1371/journal.pone.0134303.

[28] H. Yoshihara, J. Wakamatsu, F. Kawabata, S. Mori, A. Haruno, T. Hayashi, T. Sekiguchi, W. Mizunoya, R. Tatsumi, T. Ito, Y. Ikeuchi, Beef extract supplementation increases leg muscle mass and modifies skeletal muscle fiber types in rats, J Nutr Sci Vitaminol (Tokyo) 52 (2006) 183-193. 10.3177/jnsv.52.183.

[29] C.A. Stuart, M.P. McCurry, A. Marino, M.A. South, M.E. Howell, A.S. Layne, M.W. Ramsey, M.H. Stone, Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness, J Clin Endocrinol Metab 98 (2013) 2027-2036. 10.1210/jc.2012-3876.

[30] Y. Wang, J.E. Pessin, Mechanisms for fiber-type specificity of skeletal muscle atrophy, Curr Opin Clin Nutr Metab Care 16 (2013) 243-250. 10.1097/MCO.0b013e328360272d.

[31] A.J. Wagenmakers, Protein and amino acid metabolism in human muscle, Adv Exp Med Biol 441 (1998) 307-319. 10.1007/978-1-4899-1928-1_28.

[32] Y. Shimomura, T. Murakami, N. Nakai, M. Nagasaki, R.A. Harris, Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise, J Nutr 134 (2004) 1583S-1587S. 10.1093/jn/134.6.1583S.

[33] Y. Shimomura, M. Obayashi, T. Murakami, R.A. Harris, Regulation of branched-chain amino acid catabolism: nutritional and hormonal regulation of activity and expression of the branched- chain alpha-keto acid dehydrogenase kinase, Curr Opin Clin Nutr Metab Care 4 (2001) 419-423.

[34] M. Hargreaves, L.L. Spriet, Skeletal muscle energy metabolism during exercise, Nat Metab 2 (2020) 817-828. 10.1038/s42255-020-0251-4.

[35] M.J. Rennie, A. Ahmed, S.E. Khogali, S.Y. Low, H.S. Hundal, P.M. Taylor, Glutamine metabolism and transport in skeletal muscle and heart and their clinical relevance, J Nutr 126 (1996) 1142S-1149S. 10.1093/jn/126.suppl_4.1142S.

[36] P. Felig, The glucose-alanine cycle, Metabolism 22 (1973) 179-207. 10.1016/0026- 0495(73)90269-2.

[37] J.L. Jewell, R.C. Russell, K.L. Guan, Amino acid signalling upstream of mTOR, Nat Rev Mol Cell Biol 14 (2013) 133-139. 10.1038/nrm3522.

[38] R.A. Saxton, D.M. Sabatini, mTOR Signaling in Growth, Metabolism, and Disease, Cell 169 (2017) 361-371. 10.1016/j.cell.2017.03.035.

[39] R. Wang, H. Jiao, J. Zhao, X. Wang, H. Lin, L-Arginine Enhances Protein Synthesis by Phosphorylating mTOR (Thr 2446) in a Nitric Oxide-Dependent Manner in C2C12 Cells, Oxid Med Cell Longev 2018 (2018) 7569127. 10.1155/2018/7569127.

[40] G. Bonfils, M. Jaquenoud, S. Bontron, C. Ostrowicz, C. Ungermann, C. De Virgilio, Leucyl- tRNA synthetase controls TORC1 via the EGO complex, Mol Cell 46 (2012) 105-110. 10.1016/j.molcel.2012.02.009.

[41] J.M. Han, S.J. Jeong, M.C. Park, G. Kim, N.H. Kwon, H.K. Kim, S.H. Ha, S.H. Ryu, S. Kim, Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway, Cell 149 (2012) 410-424. 10.1016/j.cell.2012.02.044.

[42] L. Chantranupong, S.M. Scaria, R.A. Saxton, M.P. Gygi, K. Shen, G.A. Wyant, T. Wang, J.W. Harper, S.P. Gygi, D.M. Sabatini, The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway, Cell 165 (2016) 153-164. 10.1016/j.cell.2016.02.035.

[43] R.A. Saxton, K.E. Knockenhauer, R.L. Wolfson, L. Chantranupong, M.E. Pacold, T. Wang, T.U. Schwartz, D.M. Sabatini, Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway, Science 351 (2016) 53-58. 10.1126/science.aad2087.

[44] R.L. Wolfson, L. Chantranupong, R.A. Saxton, K. Shen, S.M. Scaria, J.R. Cantor, D.M. Sabatini, Sestrin2 is a leucine sensor for the mTORC1 pathway, Science 351 (2016) 43-48. 10.1126/science.aab2674.

[45] X. Gu, J.M. Orozco, R.A. Saxton, K.J. Condon, G.Y. Liu, P.A. Krawczyk, S.M. Scaria, J.W. Harper, S.P. Gygi, D.M. Sabatini, SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway, Science 358 (2017) 813-818. 10.1126/science.aao3265.

[46] J.W. Jung, S.J.Y. Macalino, M. Cui, J.E. Kim, H.J. Kim, D.G. Song, S.H. Nam, S. Kim, S. Choi, J.W. Lee, Transmembrane 4 L Six Family Member 5 Senses Arginine for mTORC1 Signaling, Cell Metab 29 (2019) 1306-1319 e1307. 10.1016/j.cmet.2019.03.005.

[47] J.C. Anthony, T.G. Anthony, S.R. Kimball, T.C. Vary, L.S. Jefferson, Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation, J Nutr 130 (2000) 139-145. 10.1093/jn/130.2.139.

[48] J.C. Anthony, F. Yoshizawa, T.G. Anthony, T.C. Vary, L.S. Jefferson, S.R. Kimball, Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway, J Nutr 130 (2000) 2413-2419. 10.1093/jn/130.10.2413.

[49] K. Peyrollier, E. Hajduch, A.S. Blair, R. Hyde, H.S. Hundal, L-leucine availability regulates phosphatidylinositol 3-kinase, p70 S6 kinase and glycogen synthase kinase-3 activity in L6 muscle cells: evidence for the involvement of the mammalian target of rapamycin (mTOR) pathway in the L-leucine-induced up-regulation of system A amino acid transport, Biochem J 350 Pt 2 (2000) 361- 368.

[50] J.T. Cunningham, J.T. Rodgers, D.H. Arlow, F. Vazquez, V.K. Mootha, P. Puigserver, mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex, Nature 450 (2007) 736-740. 10.1038/nature06322.

[51] G. D'Antona, M. Ragni, A. Cardile, L. Tedesco, M. Dossena, F. Bruttini, F. Caliaro, G. Corsetti, R. Bottinelli, M.O. Carruba, A. Valerio, E. Nisoli, Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice, Cell Metab 12 (2010) 362-372. 10.1016/j.cmet.2010.08.016.

[52] P.A. Dutchak, S.J. Estill-Terpack, A.A. Plec, X. Zhao, C. Yang, J. Chen, B. Ko, R.J. Deberardinis, Y. Yu, B.P. Tu, Loss of a Negative Regulator of mTORC1 Induces Aerobic Glycolysis and Altered Fiber Composition in Skeletal Muscle, Cell Rep 23 (2018) 1907-1914. 10.1016/j.celrep.2018.04.058.

[53] M. Laplante, D.M. Sabatini, mTOR signaling at a glance, J Cell Sci 122 (2009) 3589-3594. 10.1242/jcs.051011.

[54] M. Laplante, D.M. Sabatini, mTOR signaling in growth control and disease, Cell 149 (2012) 274-293. 10.1016/j.cell.2012.03.017.

[55] C.F. Bentzinger, K. Romanino, D. Cloetta, S. Lin, J.B. Mascarenhas, F. Oliveri, J. Xia, E. Casanova, C.F. Costa, M. Brink, F. Zorzato, M.N. Hall, M.A. Ruegg, Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy, Cell Metab 8 (2008) 411-424. 10.1016/j.cmet.2008.10.002.

[56] V. Risson, L. Mazelin, M. Roceri, H. Sanchez, V. Moncollin, C. Corneloup, H. Richard- Bulteau, A. Vignaud, D. Baas, A. Defour, D. Freyssenet, J.F. Tanti, Y. Le-Marchand-Brustel, B. Ferrier, A. Conjard-Duplany, K. Romanino, S. Bauche, D. Hantai, M. Mueller, S.C. Kozma, G. Thomas, M.A. Ruegg, A. Ferry, M. Pende, X. Bigard, N. Koulmann, L. Schaeffer, Y.G. Gangloff, Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy, J Cell Biol 187 (2009) 859-874. 10.1083/jcb.200903131.

[57] C.F. Bentzinger, S. Lin, K. Romanino, P. Castets, M. Guridi, S. Summermatter, C. Handschin, L.A. Tintignac, M.N. Hall, M.A. Ruegg, Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy, Skelet Muscle 3 (2013) 6. 10.1186/2044-5040-3-6.

[58] P.J. Atherton, K. Smith, T. Etheridge, D. Rankin, M.J. Rennie, Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells, Amino Acids 38 (2010) 1533-1539. 10.1007/s00726-009-0377-x.

[59] F. Yoshizawa, H. Sekizawa, S. Hirayama, A. Hatakeyama, T. Nagasawa, K. Sugahara, Time course of leucine-induced 4E-BP1 and S6K1 phosphorylation in the liver and skeletal muscle of rats, J Nutr Sci Vitaminol (Tokyo) 47 (2001) 311-315. 10.3177/jnsv.47.311.

[60] M. Doi, I. Yamaoka, M. Nakayama, S. Mochizuki, K. Sugahara, F. Yoshizawa, Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity, J Nutr 135 (2005) 2103-2108. 10.1093/jn/135.9.2103.

[61] T.A. Gautsch, J.C. Anthony, S.R. Kimball, G.L. Paul, D.K. Layman, L.S. Jefferson, Availability of eIF4E regulates skeletal muscle protein synthesis during recovery from exercise, Am J Physiol 274 (1998) C406-414. 10.1152/ajpcell.1998.274.2.C406.

[62] Y. Sato, H. Ohtsubo, N. Nihei, T. Kaneko, Y. Sato, S.I. Adachi, S. Kondo, M. Nakamura, W. Mizunoya, H. Iida, R. Tatsumi, C. Rada, F. Yoshizawa, Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle, FASEB J 32 (2018) 1428-1439. 10.1096/fj.201700493R.

[63] W.A. LaFramboise, R.D. Guthrie, D. Scalise, V. Elborne, K.L. Bombach, C.S. Armanious, J.A. Magovern, Effect of muscle origin and phenotype on satellite cell muscle-specific gene expression, J Mol Cell Cardiol 35 (2003) 1307-1318. 10.1016/s0022-2828(03)00245-1.

[64] N. Okumura, A. Hashida-Okumura, K. Kita, M. Matsubae, T. Matsubara, T. Takao, K. Nagai, Proteomic analysis of slow- and fast-twitch skeletal muscles, Proteomics 5 (2005) 2896-2906. 10.1002/pmic.200401181.

[65] C.A. Goodman, D.M. Mabrey, J.W. Frey, M.H. Miu, E.K. Schmidt, P. Pierre, T.A. Hornberger, Novel insights into the regulation of skeletal muscle protein synthesis as revealed by a new nonradioactive in vivo technique, FASEB J 25 (2011) 1028-1039. 10.1096/fj.10-168799.

[66] S. Murakami, H. Fujino, I. Takeda, R. Momota, K. Kumagishi, A. Ohtsuka, Comparison of capillary architecture between slow and fast muscles in rats using a confocal laser scanning microscope, Acta Med Okayama 64 (2010) 11-18. 10.18926/AMO/32859.

[67] S. Miller, D. Chinkes, D.A. MacLean, D. Gore, R.R. Wolfe, In vivo muscle amino acid transport involves two distinct processes, Am J Physiol Endocrinol Metab 287 (2004) E136-141. 10.1152/ajpendo.00092.2004.

[68] S.M. Hughes, K. Koishi, M. Rudnicki, A.M. Maggs, MyoD protein is differentially accumulated in fast and slow skeletal muscle fibres and required for normal fibre type balance in rodents, Mech Dev 61 (1997) 151-163. 10.1016/s0925-4773(96)00631-4.

[69] M. Ekmark, Z.A. Rana, G. Stewart, D.G. Hardie, K. Gundersen, De-phosphorylation of MyoD is linking nerve-evoked activity to fast myosin heavy chain expression in rodent adult skeletal muscle, J Physiol 584 (2007) 637-650. 10.1113/jphysiol.2007.141457.

[70] R. Macharia, A. Otto, P. Valasek, K. Patel, Neuromuscular junction morphology, fiber-type proportions, and satellite-cell proliferation rates are altered in MyoD(-/-) mice, Muscle Nerve 42 (2010) 38-52. 10.1002/mus.21637.

[71] J. Talvas, A. Obled, P. Fafournoux, S. Mordier, Regulation of protein synthesis by leucine starvation involves distinct mechanisms in mouse C2C12 myoblasts and myotubes, J Nutr 136 (2006) 1466-1471. 10.1093/jn/136.6.1466.

[72] X. Sun, M.B. Zemel, Leucine modulation of mitochondrial mass and oxygen consumption in skeletal muscle cells and adipocytes, Nutr Metab (Lond) 6 (2009) 26. 10.1186/1743-7075-6-26.

[73] M.S. Yoon, K. Son, E. Arauz, J.M. Han, S. Kim, J. Chen, Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling, Cell Rep 16 (2016) 1510-1517. 10.1016/j.celrep.2016.07.008.

[74] F. Yoshizawa, S. Mochizuki, K. Sugahara, Differential dose response of mTOR signaling to oral administration of leucine in skeletal muscle and liver of rats, Biosci Biotechnol Biochem 77 (2013) 839-842. 10.1271/bbb.120737.

[75] M.S. Yoon, J. Chen, Distinct amino acid-sensing mTOR pathways regulate skeletal myogenesis, Mol Biol Cell 24 (2013) 3754-3763. 10.1091/mbc.E13-06-0353.

[76] Y. Ge, J. Chen, Mammalian target of rapamycin (mTOR) signaling network in skeletal myogenesis, J Biol Chem 287 (2012) 43928-43935. 10.1074/jbc.R112.406942.

[77] E. Erbay, I.H. Park, P.D. Nuzzi, C.J. Schoenherr, J. Chen, IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrients, J Cell Biol 163 (2003) 931-936. 10.1083/jcb.200307158.

[78] S.C. Bodine, T.N. Stitt, M. Gonzalez, W.O. Kline, G.L. Stover, R. Bauerlein, E. Zlotchenko, A. Scrimgeour, J.C. Lawrence, D.J. Glass, G.D. Yancopoulos, Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo, Nat Cell Biol 3 (2001) 1014-1019. 10.1038/ncb1101-1014.

[79] C. Rommel, S.C. Bodine, B.A. Clarke, R. Rossman, L. Nunez, T.N. Stitt, G.D. Yancopoulos, D.J. Glass, Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways, Nat Cell Biol 3 (2001) 1009-1013. 10.1038/ncb1101-1009.

[80] R.A. Saxton, L. Chantranupong, K.E. Knockenhauer, T.U. Schwartz, D.M. Sabatini, Mechanism of arginine sensing by CASTOR1 upstream of mTORC1, Nature 536 (2016) 229-233. 10.1038/nature19079.

[81] J. Ye, W. Palm, M. Peng, B. King, T. Lindsten, M.O. Li, C. Koumenis, C.B. Thompson, GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2, Genes Dev 29 (2015) 2331-2336. 10.1101/gad.269324.115.

[82] M.S. Yoon, J. Chen, PLD regulates myoblast differentiation through the mTOR-IGF2 pathway, J Cell Sci 121 (2008) 282-289. 10.1242/jcs.022566.

[83] N. Quan, W. Sun, L. Wang, X. Chen, J.S. Bogan, X. Zhou, C. Cates, Q. Liu, Y. Zheng, J. Li, Sestrin2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism, FASEB J 31 (2017) 4153-4167. 10.1096/fj.201700063R.

[84] L. Lenhare, B.M. Crisol, V.R.R. Silva, C.K. Katashima, A.V. Cordeiro, K.D. Pereira, A.D. Luchessi, A.S.R. da Silva, D.E. Cintra, L.P. Moura, J.R. Pauli, E.R. Ropelle, Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice, Exp Gerontol 97 (2017) 17-21. 10.1016/j.exger.2017.07.009.

[85] K. Duvel, J.L. Yecies, S. Menon, P. Raman, A.I. Lipovsky, A.L. Souza, E. Triantafellow, Q. Ma, R. Gorski, S. Cleaver, M.G. Vander Heiden, J.P. MacKeigan, P.M. Finan, C.B. Clish, L.O. Murphy, B.D. Manning, Activation of a metabolic gene regulatory network downstream of mTOR complex 1, Mol Cell 39 (2010) 171-183. 10.1016/j.molcel.2010.06.022.

[86] S.M. Blattler, F. Verdeguer, M. Liesa, J.T. Cunningham, R.O. Vogel, H. Chim, H. Liu, K. Romanino, O.S. Shirihai, F. Vazquez, M.A. Ruegg, Y. Shi, P. Puigserver, Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle, Mol Cell Biol 32 (2012) 3333-3346. 10.1128/MCB.00337-12.

[87] R. Suzuki, Y. Sato, K.A. Obeng, D. Suzuki, Y. Komiya, S.-i. Adachi, F. Yoshizawa, Y. Sato, Energy metabolism profile of the effects of amino acid treatment on skeletal muscle cells: Leucine inhibits glycolysis of myotubes, Nutrition (2020). 10.1016/j.nut.2020.110794.

[88] S.C. Tso, W.J. Gui, C.Y. Wu, J.L. Chuang, X. Qi, K.J. Skvora, K. Dork, A.L. Wallace, L.K. Morlock, B.H. Lee, S.M. Hutson, S.C. Strom, N.S. Williams, U.K. Tambar, R.M. Wynn, D.T. Chuang, Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched-chain alpha-ketoacid dehydrogenase kinase, J Biol Chem 289 (2014) 20583-20593. 10.1074/jbc.M114.569251.

[89] W. Mizunoya, A. Tashima, Y. Sato, R. Tatsumi, Y. Ikeuchi, The growth-promoting activity of egg white proteins in the C2C12 myoblast cell line, Anim Sci J 86 (2015) 194-199. 10.1111/asj.12257.

[90] Y. Sato, Y. Sato, K.A. Obeng, F. Yoshizawa, Acute oral administration of L-leucine upregulates slow-fiber- and mitochondria-related genes in skeletal muscle of rats, Nutr Res 57 (2018) 36-44. 10.1016/j.nutres.2018.05.006.

[91] T.A. Miettinen, I.M. Penttila, Leucine and mevalonate as precursors of serum cholesterol in man, Acta Med Scand 184 (1968) 159-164. 10.1111/j.0954-6820.1968.tb02437.x.

[92] J.L. Bowtell, S. Marwood, M. Bruce, D. Constantin-Teodosiu, P.L. Greenhaff, Tricarboxylic acid cycle intermediate pool size: functional importance for oxidative metabolism in exercising human skeletal muscle, Sports Med 37 (2007) 1071-1088. 10.2165/00007256-200737120-00005.

[93] D. Malinska, A.P. Kudin, M. Bejtka, W.S. Kunz, Changes in mitochondrial reactive oxygen species synthesis during differentiation of skeletal muscle cells, Mitochondrion 12 (2012) 144-148. 10.1016/j.mito.2011.06.015.

[94] J. Averous, J.C. Gabillard, I. Seiliez, D. Dardevet, Leucine limitation regulates myf5 and myoD expression and inhibits myoblast differentiation, Exp Cell Res 318 (2012) 217-227. 10.1016/j.yexcr.2011.10.015.

[95] Y. Duan, F. Li, Y. Li, Y. Tang, X. Kong, Z. Feng, T.G. Anthony, M. Watford, Y. Hou, G. Wu, Y. Yin, The role of leucine and its metabolites in protein and energy metabolism, Amino Acids 48 (2016) 41-51. 10.1007/s00726-015-2067-1.

[96] Z.N. Dhanani, G. Mann, O.A.J. Adegoke, Depletion of branched-chain aminotransferase 2 (BCAT2) enzyme impairs myoblast survival and myotube formation, Physiol Rep 7 (2019) e14299. 10.14814/phy2.14299.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る