Sulforaphane prevents dexamethasone-induced muscle atrophy via regulation of the Akt/Foxo1 axis in C2C12 myotubes

Abstract

Muscle atrophy occurs in various catabolic conditions, including hormone imbalance, severe injury, sepsis, cancer, and aging. Dexamethasone (DEX) is a synthetic glucocorticoid and is used an anti-inflammatory agent. However, when chronically used, it is accompanied by side effects, such as, muscle atrophy, diabetes mellitus, and obesity. In this study, we investigated the effect of sulforaphane (SFN) on DEX-induced muscle atrophy and the underlying mechanisms involved. DEX induced muscle atrophy was accompanied by increased muscle specific ubiquitin E3 ligase markers, such as, Atrogin-1 and myostatin, and decreased MyoD in C2C12 myotubes. To investigate the role played by SFN in DEX-induced muscle atrophy, we quantified mRNA levels of muscle atrophy markers, protein synthesis using a puromycin incorporation assay, protein degradation by ubiquitination, and myotube diameters by PAS staining in C2C12 myotubes co-treated with DEX and SFN. Interestingly, SFN effectively prevented myostatin and Atrogin-1 mRNA upregulations by DEX, increased the mRNA level of MyoD, and consequently, reduced protein degradation. Furthermore, SFN enhanced protein synthesis through a Foxo-dependent pathway by activating Akt, and thus, increased myotube diameters. These results show SFN inhibits DEX-induced muscle atrophy in C2C12 myotubes via Akt/Foxo signaling.