Resveratrol promotes myogenesis and hypertrophy in murine myoblasts
Anna Montesano1,2,3, Livio Luzi1,2,3, Pamela Senesi1,2,3, Nausicaa Mazzocchi1,2,3, Ileana Terruzzi1,2,3
1Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; 2Research Centre, San Donato Hospital and Scientific Institute, San Donato Hospital and Scientific Institute, Milan, Italy; 3Nutrition-Metabolism Unit , San Raffaele Scientific Institute, Milan, Italy
Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications.
Resveratrol (RSV), natural polyphenol found in grapes and in other fruits, has a plethora of health benefits in a variety of human diseases: cardio- and neuroprotection, immune regulation, cancer chemoprevention, DNA repair, activation of Sirtuins (SIRT 1), prevention of mitochondrial disorder, avoidance of obesity-related disease. Inskeletal muscle, RSV acts on protein catabolism and muscle function, conferring resistance against oxidative stress, injury and cell death, but itsaction mechanismsand protein targets in myogenesis process are not completely known. Myogenesis is a dynamic multistep process regulated by Myogenic Regulator Factors (MRFs), responsible of the commitment of myogenic cell into skeletal muscle: mononucleated undifferentiated myoblasts break free from cell cycle, elongate and fuse to form multinucleated myotubes. Skeletal muscle hypertrophy can be definite as a result of an increase in the size of pre-existing skeletal muscle fibers accompanied by enhanced protein synthesis, regulated by Insulin Like Growth Factor 1 (IGF-1) and the PI3-K/AKT signaling pathways.
Aim of this work was the study of RSV effects on cell cycle regulation, differentiation process and hypertrophy in C2C12 murine cells.
To study proliferation, cells were incubated in growth medium with/without RSV (0.1 or 25 μM) for 24, 48, 72 hours. To examine differentiation, at 70% confluence, cells were maintained in growth medium or transferred in differentiation medium both with/without RSV (0.1 or 25 μM) for 24, 48, 72, 96 hours. After 96 hours of differentiation, hypertrophy genesis in neo-formed myotubes was analyzed.
Datashowed that RSV could regulate cell cycle exit and induce C2C12 muscle differentiation. Furthermore, RSV might control Myogenic Regulatory Factors expression and muscle-specific proteins synthesis. In late differentiation, we evaluated the positive effects of RSV on hypertrophy: RSV increased AMPK, IGF-1 and ERK 1/2 proteins content and induced hypertrophic morphological changes in neo-formed myotubes modulating cytoskeletal proteins expression.
RSV might control cell cycle to promote myogenesis and hypertrophy in vitro, opening a novel field of application of RSV in clinical conditions characterized by chronic functional and morphological muscle impairment.