Induction of mitochondrial biogenesis protects against caspase-dependent and caspase-independent apoptosis in L6 myoblasts.

摘要: Apoptotic signaling plays an important role in skeletal muscle degradation, atrophy, and dysfunction. Mitochondria are central executers of apoptosis by directly participating caspase-dependent caspase-independent cell death signaling. Given the apoptotic mitochondria, altering mitochondrial content could influence apoptosis. Therefore, we examined direct effect modest, but physiological increases biogenesis on using a culture approach. Treatment L6 myoblasts with SNAP or AICAR (5h/day for 5days) significantly increased PGC-1, AIF, cytochrome c, MnSOD protein as well MitoTracker staining. Following induction biogenesis, displayed decreased sensitivity to reduced caspase-3 caspase-9 activation following exposure staurosporine (STS) C2-ceramide. higher also exhibited AIF release hydrogen peroxide (H2O2). Analysis several key regulatory proteins (ARC, Bax, Bcl-2, XIAP), antioxidant (catalase, MnSOD, CuZnSOD), reactive oxygen species (ROS) measures (DCF MitoSOX fluorescence) revealed that these mechanisms were not responsible observed cellular protection. However, less sensitive Ca(2+)-induced permeability transition pore formation (mPTP) membrane depolarization. Collectively, data demonstrate at levels provides protection against decreasing through influencing Ca(2+)-mediated events. increasing biogenesis/content may represent potential therapeutic approach disorders displaying