title: Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?
abstract: 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 glucocorticoi - 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.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Poland. orzechowski@alpha.sggw.waw.pl
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Orzechowski
authors.forename: Jean
authors.initials: J
authors.lastname: Grizard
authors.forename: Michał
authors.initials: M
authors.lastname: Jank
authors.forename: Barbara
authors.initials: B
authors.lastname: Gajkowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lokociejewska
authors.forename: Magda
authors.initials: M
authors.lastname: Zaron-Teperek
authors.forename: Michał
authors.initials: M
authors.lastname: Godlewski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects*; D009124:Muscle Proteins / Q000096:biosynthesis; D051381:Rats; D013997:Time Factors
chemical_list: D009124:Muscle Proteins; D003907:Dexamethasone; D006861:Hydrogen Peroxide