The role of whey protein in myogenic differentiation
Main Article Content
Keywords
C2C12, myoblast differentiation, whey protein
Abstract
Whey protein has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that whey protein would regulate muscle cell differentiation. Adding various concentrations of whey protein to C2C12 myoblasts induced cell differentiation and MyoD (myogenic differentiation protein) expression as well as the phosphorylation of AKT (protein kinase B). Whey protein-induced differentiation-specific markers increased the enzymatic activities of creatine kinase and citrate synthase and the expression of muscle-specific microRNA. Whey protein elevated AKT phosphorylation on Thr308 and Ser473, which was inhibited by LY294002 (a non-selective phosphoinositide 3-kinases inhibitor), suggesting that whey protein acts via PI3K (phosphatidylinositol 3-kinase). Blocking of the PI3K/AKT pathway with specific inhibitors revealed its requirement in mediating the promotive effects of whey protein on C2C12 cell differentiation. These effects of whey protein on myoblast differentiation suggest its positive influence in preventing muscle atrophy.
References
Dogra, C., Changotra, H., Mohan, S. and Kumar, A., 2006. Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis through sustained activation of nuclear factor-kappaB and degradation of MyoD protein. Journal of Biological Chemistry 281: 10327–10336. 10.1074/jbc.M511131200
Griffen, C., Duncan, M., Hattersley, J., Weickert, M.O., Dallaway, A. and Renshaw, D., 2022. Effects of resistance exercise and whey protein supplementation on skeletal muscle strength, mass, physical function, and hormonal and inflammatory biomarkers in healthy active older men: a randomised, double-blind, placebo-controlled trial. Experimental Gerontology 158: 111651–111657. 10.1016/j.exger.2021.111651
Hernández-Hernández, J.M., García-González, E.G., Brun, C.E. and Rudnicki, M.A., 2017. The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration. Seminars in Cell & Developmental Biology 72: 10–18. 10.1016/j.semcdb.2017.11.010
Kwak, S.S., Kang, K.H., Kim, S., Lee, S., Lee, J.-H., Kim, J.W., Byun, B., Meadows, G.G. and Joe, C.O. et al, 2016. Amino acid-dependent NPRL2 interaction with Raptor determines mTOR Complex 1 activation. Cellular Signalling 28(2): 32–41. 10.1016/j.cellsig.2015.11.008
Lee, S.-J., Bae, J.H., Lee, H., Lee, H., Park, J., Kang, J.-S. and Bae, G.-U., 2019. Ginsenoside Rg3 upregulates myotube formation and mitochondrial function, thereby protecting myotube atrophy induced by tumor necrosis factor-alpha. Journal of Ethnopharmacology 242: 112054–112059. 10.1016/j.jep.2019.112054
Motaei, J., Yaghmaie, M., Ahmadvand, M., Pashaiefar, H. and Kerachian, M.A., 2019. MicroRNAs as potential diagnostic, prognostic, and predictive biomarkers for acute graft-versus-host disease. Biology of Blood and Marrow Transplantation 25(12): e375–e386. 10.1016/j.bbmt.2019.08.004
Qin, Y., Peng, Y., Zhao, W., Pan, J., Ksiezak-Reding, H., Cardozo, C., Wu, Y., Pajevic, P.D., Bonewald, L.F., Bauman, W.A. and Qin, W. et al, 2017. Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: a novel mechanism in muscle-bone communication. Journal of Biological Chemistry 292(26): 11021–11033. 10.1074/jbc.M116.770941
Rommel, C., Bodine, S.C., Clarke, B.A., Rossman, R., Nunez, L., Stitt, T.N., Yancopoulos, G.D. and Glass, D.J., 2001. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nature Cell Biology 3: 1009–1013. 10.1038/ncb1101-1009
Rosenberg, M.I., Georges, S.A., Asawachaicharn, A., Analau, E. and Tapscott, S.J., 2006. MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206. Journal of Cell Biology 175: 77–85. 10.1083/jcb.200603039
Sans, M.D., Crozier, S.J., Vogel, N.L., D’Alecy, L.G. and Williams, J.A., 2021. Dietary protein and amino acid deficiency inhibit pancreatic digestive enzyme mRNA translation by multiple mechanisms. Cellular and Molecular Gastroenterology and Hepatology 11(1): 99–115. 10.1016/j.jcmgh.2020.07.008
Seale, P. and Rudnicki, M.A., 2000. A new look at the origin, function, and “stem-cell” status of muscle satellite cells. Developmental Biology 218: 115–124. 10.1006/dbio.1999.9565
Taylor, M.V. and Hughes, S.M., 2017. Mef2 and the skeletal muscle differentiation program. Seminars in Cell & Developmental Biology 72: 33–44. 10.1016/j.semcdb.2017.11.020
Thalacker-Mercer, A., Riddle, E. and Barre, L., 2020. Chapter two–protein and amino acids for skeletal muscle health in aging. Advances in Food and Nutrition Research 91: 29–64. 10.1016/bs.afnr.2019.08.002
Vaisid, T. and Kosower, N.S., 2013. Calpastatin is upregulated in non-immune neuronal cells via toll-like receptor 2 (TLR2) pathways by lipid-containing agonists. Biochimica et Biophysica Acta (BBA)–Molecular Cell Research 1833(10): 2369–2377. 10.1016/j.bbamcr.2013.06.006
Wang, J., Yang, L.Z., Zhang, J.S., Gong, J.X., Wang, Y.H., Zhang, C.L., Chen, H. and Fang, X.T., 2018. Effects of microRNAs on skeletal muscle development. Gene 668: 107–113. 10.1016/j.gene.2018.05.039
Zhang, H., Wang, Y., Tang, X., Dou, S., Sun, Y., Zhang, Q. and Lu, J., 2021. Combinatorial regulation of gene expression by uORFs and microRNAs in Drosophila. Science Bulletin 66(3): 225–228. 10.1016/j.scib.2020.10.012
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