Role of SIRT2 in regulating the dexamethasone-activated autophagy pathway in skeletal muscle atrophy

The proteolytic autophagy system is involved in a major regulatory pathway in dexamethasone (Dex)-induced muscle atrophy. Sirtuin 2 (SIRT2) is known to modulate autophagy signaling, exerting effects in skeletal muscle atrophy. We examined the effects of SIRT2 on autophagy in Dex-induced myoatrophy. Tostudy this, mice were randomly distributed among the normal, Dex, and sirtinol groups. C2C12 cells were differentiated into myotubes and transduced with lentivirus carrying Sirt2-green fluorescent protein (GFP) or Sirt2 short hairpin RNA (Sirt2-shRNA)-GFP. To evaluate the mass and function of skeletal muscles, we measured myofiber cross-sectional area, myotube size, gastrocnemius (GA) muscle wet mass: body mass ratio (%), and time to exhaustion. The expression levels of SIRT2, myosin heavy chain, microtubule- associated protein 1 light chain 3 (LC3), and Beclin-1 were measured using Western blotting and quantitative reverse transcription polymerase chain reaction. Inhibition of SIRT2 markedly attenuated GA muscle mass and endurance capacity. The same phenotype was observed in Sirt2-shRNA-treated myotubes, as evidenced by their decreased size. Conversely, overexpression of SIRT2 alleviated Dex-induced myoatrophy in vitro. Moreover, SIRT2 negatively regulated the expression of LC3b and Beclin-1 in skeletal muscles. These findings suggest that SIRT2 activation protects myotubes against Dex-induced atrophy through inhibition of the autophagy system; this phenomenon may serve as a target for treating glucocorticoid-induced myopathy.