Cellular effects of resveratrol in skeletal muscle

Naylor, Amie J. Dirks

doi:10.1016/j.lfs.2009.02.011

Cited by 37 publications

(27 citation statements)

References 25 publications

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“…Increasing evidence suggests that RSV has an active role in skeletal muscle differentiation [26,41-46]. However, the mechanisms underlying these RSV-induced adaptations have not been completely elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

“…But, since RSV has been shown to act on skeletal muscle metabolism and function [41-45], less attention has been given to its effects on myogenesis [46]. …”

Section: Introductionmentioning

confidence: 99%

Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

et al. 2013

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“…It has been shown to protect against cardiovascular diseases, type II diabetes and neurological diseases. In addition, several effects on skeletal muscle, such as an inhibition of protein catabolism, an enhancement of glucose transport and protection against oxidative stress, injury and cells death have also been reported (36). However, it is worth noting that resveratrol is also an inductor of autophagy, a critical player in the pathogenesis of GSDII (37).…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of the common c.-32-13T>G mutation of GAA gene: identification of potential therapeutic agents

Dardis

Zanin

Zampieri

et al. 2013

Nucleic Acids Research

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Glycogen storage disease type II is a lysosomal storage disorder due to mutations of the GAA gene, which causes lysosomal alpha-glucosidase deficiency. Clinically, glycogen storage disease type II has been classified in infantile and late-onset forms. Most late-onset patients share the leaky splicing mutation c.-32-13T>G. To date, the mechanism by which the c.-32-13T>G mutation affects the GAA mRNA splicing is not fully known. In this study, we demonstrate that the c.-32-13T>G mutation abrogates the binding of the splicing factor U2AF65 to the polypyrimidine tract of exon 2 and that several splicing factors affect exon 2 inclusion, although the only factor capable of acting in the c.-32-13 T>G context is the SR protein family member, SRSF4 (SRp75). Most importantly, a preliminary screening using small molecules described to be able to affect splicing profiles, showed that resveratrol treatment resulted in a significant increase of normal spliced GAA mRNA, GAA protein content and activity in cells transfected with a mutant minigene and in fibroblasts from patients carrying the c-32-13T>G mutation. In conclusion, this work provides an in-depth functional characterization of the c.-32-13T>G mutation and, most importantly, an in vitro proof of principle for the use of small molecules to rescue normal splicing of c.-32-13T>G mutant alleles.

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“…Specifically, Chi et al (Chi et al, 2007) found that resveratrol increased expression of the glucose transporter GLUT4 in the soleus of diabetic rats but had no effect in the muscles of healthy rats. Such findings further suggest a need for high-fat conditions in order to elicit the true beneficial effects of this compound (Dirks Naylor, 2009). …”

Section: Alternative Interventionsmentioning

confidence: 99%

Of mice and men: The benefits of caloric restriction, exercise, and mimetics

Mercken

Carboneau

Krzysik-Walker

et al. 2012

Ageing Research Reviews

257

226

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During aging there is an increasing imbalance of energy intake and expenditure resulting in obesity, frailty, and metabolic disorders. For decades, research has shown that caloric restriction (CR) and exercise can postpone detrimental aspects of aging. These two interventions invoke a similar physiological signature involving pathways associated with stress responses and mitochondrial homeostasis. Nonetheless, CR is able to delay aging processes that result in an increase of both mean and maximum lifespan, whereas exercise primarily increases healthspan. Due to the strict dietary regime necessary to achieve the beneficial effects of CR, most studies to date have focused on rodents and non-human primates. As a consequence, there is vast interest in the development of compounds such as resveratrol, metformin and rapamycin that would activate the same metabolic- and stress-response pathways induced by these interventions without actually restricting caloric intake. Therefore the scope of this review is to (i) describe the benefits of CR and exercise in healthy individuals, (ii) discuss the role of these interventions in the diseased state, and (iii) examine some of the promising pharmacological alternatives such as CR- and exercise-mimetics.

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Cellular effects of resveratrol in skeletal muscle

Cited by 37 publications

References 25 publications

Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

Resveratrol promotes myogenesis and hypertrophy in murine myoblasts

Functional characterization of the common c.-32-13T>G mutation of GAA gene: identification of potential therapeutic agents

Of mice and men: The benefits of caloric restriction, exercise, and mimetics

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