Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?
Reproduction nutrition development (Print)
The hypothetical involvement of H 2 O 2 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 H 2 O 2 . Micromolar concentrations of H 2 O 2 inhibited DNA while stimulating protein synthesis. At the millimolar level, H 2 O 2 led to cell death by apoptosis. Synthetic glucocorticoid
... asone (Dex) was shown to effect muscle cell fate similarly to H 2 O 2 . Chronic treatment with H 2 O 2 or Dex dose-dependently accelerated either the formation of myotubes or cell elimination. Dexinduced 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 H 2 O 2 directly influences myogenesis and muscle cell elimination. Moreover, H 2 O 2 can be considered as the potent mediator of glucocorticoid-dependent effects on muscle cells. muscle cell / hydrogen peroxide / differentiation / cell death Reprod. Nutr. Dev. 42 (2002) 197-216 197