Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

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.

Redox Control of Skeletal Muscle Regeneration

“…Similar results were observed on myogenic differentiation in vitro by using the antioxidant resveratrol (160,224).…”

Blunted hypertrophic response in old mouse muscle is associated with a lower satellite cell density and is not alleviated by resveratrol

“…18 differentiation (Kaminski et al, 2012;Montesano et al, 2013) and to block the proliferation (Montesano et al, 2013) we did not find an altered expression of Id2, MyoD and myogenin, important regulators of SC proliferation and differentiation. Resveratrol did, however, decrease total caspase-3 protein content, which is in accordance with others where resveratrol decreased mitochondrial caspase-dependent apoptotic signaling pathways (Bennett et al, 2013;Marzetti et al, 2011).…”

“…Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenol with anti-oxidant properties that has been associated with a number of health benefits. Its effect on myoblasts in particular seems to be anti-proliferative and pro-differentiation (Kaminski et al, 2012;Montesano et al, 2013;Saini et al, 2012).…”

Effect of anthocyanidins on myogenic differentiation in induced and non-induced primary myoblasts from rainbow trout ( Oncorhynchus mykiss )

“…Committed myoblast could remain responsive to environmental stimuli in order to determine cell fate between progressing toward terminal differentiation and keeping the cell poised to rapidly differentiate (Chapalamadugu et al, 2009;Olguín et al, 2004;Olguín and Pisconti, 2012). Previous studies have reported that polyphenols including resveratrol can either promote or inhibit myogenic differentiation in a dose-dependent manner in C2C12 myoblasts (Abdulla et al, 2013;Bosutti and Degens, 2015;Kaminski et al, 2012;Montesano et al, 2013). Low resveratrol concentrations (10 to 25 μM) have been reported to stimulate myoblast cell cycle arrest and favor further commitment toward terminal differentiation in C2C12 myoblasts (Bosutti and Degens, 2015;Kaminski et al, 2012;Montesano et al, 2013).…”