Abstract
BackgroundNutrigenomics 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.MethodsTo 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.ResultsData 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.ConclusionsRSV 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.
Highlights
Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications
The second phase is the commitment of myogenic cells into skeletal muscle cells: mononucleated undifferentiated myoblasts break free from the cell cycle, cease to divide, elongate and fuse into multinucleated myotubes [1,2,3,9,10,11,12] (Figure 1A)
In the present work we investigated potential mechanisms mediating the effects of two different doses of Resveratrol (0.1 μM and 25 μM) on cell cycle regulation, skeletal muscle differentiation and during the genesis of hypertrophy in C2C12 myoblastic cells (Figure 1B)
Summary
Nutrigenomics elucidate the ability of bioactive food components to influence gene expression, protein synthesis, degradation and post-translational modifications. 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. The first is the induction of muscle-specific genes expression by Myogenic Regulatory Factors (MRFs), such as Myf-5, MyoD, Myf-6 and Myogenin [1,2,3,4,5,6,7,8] (Figure 1A). The second phase is the commitment of myogenic cells into skeletal muscle cells: mononucleated undifferentiated myoblasts break free from the cell cycle, cease to divide, elongate and fuse into multinucleated myotubes [1,2,3,9,10,11,12] (Figure 1A). Progression through cell cycle phases is dependent on consecutive activation and inhibition of phosphoproteins by cyclindependent kinases (CDKs) complexed with their activators cyclins [1,4,5,13]
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