Resveratrol Blocks Glucocorticoid‐induced Muscle Wasting in L6 Cultured Myotubes

Abstract

Muscle proteolysis during sepsis and other catabolic conditions is, at least in part, regulated by glucocorticoids. Dexamethasone-treated myotubes are a commonly used in vitro model of muscle wasting. We reported recently decreased expression and activity of histone deacetylases (HDACs) including Sirtuin (SIRT) 1 are involved in the development of muscle wasting. We tested the hypothesis that treatment with the HDAC/SIRT1 activator resveratrol would prevent glucocorticoid-induced muscle wasting in cultured myotubes. L6 myotubes were treated for 24 h with 1 μM dexamethasone in the absence or presence of resveratrol (100 μM). After treatment for 24 h, myotubes were harvested for determination of atrogin-1 and MuRF1 levels by real-time PCR and Western blot. Myotube cultures were photographed under a phase contrast microscope at 100X magnification for determination of myotube size. Treatment with dexamethasone resulted in increased expression of atrogin-1 and MuRF1, and this was accompanied by a 25–30% reduction of myotube diameter. Resveratrol treatment inhibited the dexamethasone-induced increases in atrogin-1 and MuRF1 expression and reduction in myotube size. Results suggest that resveratrol treatment may prevent glucocorticoid-induced muscle wasting. HDAC/SIRT1 activation may be a novel therapeutic approach in combating muscle wasting conditions. Supported by R01 NR008545 from the NIH.