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Open Access Research

Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

Anna Montesano1, Livio Luzi12, Pamela Senesi12, Nausicaa Mazzocchi3 and Ileana Terruzzi3*

Author Affiliations

1 Department of Biomedical Sciences for Health, University of Milan, Milan, Italy

2 Metabolism Research Centre and Department of Endocrinology and Metabolic Diseases, San Donato Hospital and Scientific Institute, Milan, Italy

3 Division of Metabolic and Cardiovascular Sciences, Metabolism, Nutrigenomics and Cellular Differentiation Unit, DIBIT-San Raffaele Scientific Institute, Milan, Italy

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Journal of Translational Medicine 2013, 11:310  doi:10.1186/1479-5876-11-310

Published: 13 December 2013

Abstract

Background

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, prevention of mitochondrial disorder, avoidance of obesity-related diseases. In skeletal muscle, RSV acts on protein catabolism and muscle function, conferring resistance against oxidative stress, injury and cell death, but its action mechanisms and 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 defined as a result of an increase in the size of pre-existing skeletal muscle fibers accompanied by increased protein synthesis, mainly regulated by Insulin Like Growth Factor 1 (IGF-1), PI3-K/AKT signaling pathways.

Aim of this work was the study of RSV effects on proliferation, differentiation process and hypertrophy in C2C12 murine cells.

Methods

To study proliferative phase, cells were incubated in growth medium with/without RSV (0.1 or 25 μM) until reaching sub confluence condition (24, 48, 72 h). To examine differentiation, at 70% confluence, cells were transferred in differentiation medium both with/without RSV (0.1 or 25 μM) for 24, 48, 72, 96 hours. After 72 hours of differentiation, the genesis of hypertrophy in neo-formed myotubes was analyzed.

Results

Data showed that RSV regulates cell cycle exit and induces C2C12 muscle differentiation. Furthermore, RSV might control MRFs and muscle-specific proteins synthesis. In late differentiation, RSV has positive effects on hypertrophy: RSV stimulates IGF-1 signaling pathway, in particular AKT and ERK 1/2 protein activation, AMPK protein level and induces hypertrophic morphological changes in neo-formed myotubes modulating cytoskeletal proteins expression.

Conclusions

RSV might control cell cycle promoting myogenesis and hypertrophy in vitro, opening a novel field of application of RSV in clinical conditions characterized by chronic functional and morphological muscle impairment.

Keywords:
Resveratrol; Proliferation; Myoblast; Differentiation; Myocyte; Myogenic Regulatory Factors; Myotube; Hypertrophy