Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?

The hypothetical involvement of H₂O₂ in dexamethasone-mediated regulation of muscle cell differentiation and elimination was studied. Rat L6 myoblasts and mouse C2C12 satellite cells were chosen for acute (24 h) and chronic (5 or 10 day) experiments. Mitogenicity and anabolism were both affected by H₂O₂. Micromolar concentrations of H₂O₂ inhibited DNA while stimulating protein synthesis. At the millimolar level, H₂O₂ led to cell death by apoptosis. Synthetic glucocorticoid - dexamethasone (Dex) was shown to effect muscle cell fate similarly to H₂O₂. Chronic treatment with H₂O₂ or Dex dose-dependently accelerated either the formation of myotubes or cell elimination. Dex-induced cell death slightly differed from classical apoptosis and was featured by the symptoms of cell senescence such as extensive cytoplasm vacuolisation, accumulation of inclusion-bodies and lack of low molecular weight oligonucleosomal DNA fragmentation but chromatin condensation. Antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase) abrogated Dex-dependent cell death. We conclude that H₂O₂ directly influences myogenesis and muscle cell elimination. Moreover, H₂O₂ can be considered as the potent mediator of glucocorticoid-dependent effects on muscle cells.