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

• Published in: Reproduction, nutrition, development Vol. 42; no. 3; pp. 197 - 216
• Main Authors: Orzechowski, A. ((Warsaw Agricultural University (Pologne). Faculty of Veterinary Medicine, Department of Physiological Sciences)), Grizard, J, Jank, M, Gajkowska, B, Lokociejewska, M, Zaron-Teperek, M, Godlewski, M
• Format: Journal Article
• Language: English
• Published: Les Ulis EDP Sciences 01.05.2002
• Subjects: Agricultural sciences; ANIMAL DE LABORATOIRE; Animal production studies; ANIMALES DE LABORATORIO; Animals; APOPTOSE; APOPTOSIS; Apoptosis - drug effects; Biological and medical sciences; CELL DIFFERENTIATION; Cell Division - drug effects; Cell Survival - drug effects; Cell Transformation, Neoplastic - drug effects; Cells, Cultured; CORTICOIDES; CORTICOIDS; Dexamethasone - toxicity; DIFERENCIACION CELULAR; DIFFERENCIATION CELLULAIRE; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; FIBRAS MUSCULARES; FIBRE MUSCULAIRE; Fundamental and applied biological sciences. Psychology; HYDROGEN PEROXIDE; Hydrogen Peroxide - pharmacology; LABORATORY ANIMALS; Life Sciences; Mice; MUSCLE; Muscle Cells - cytology; Muscle Cells - drug effects; MUSCLE FIBRES; Muscle Proteins - biosynthesis; MUSCLES; MUSCULOS; PEROXIDO DE HIDROGENO; PEROXYDE D'HYDROGENE; RAT; RATA; RATS; Striated muscle. Tendons; Time Factors; Vertebrates: osteoarticular system, musculoskeletal system; Corticosteroid; Dexamethasone; differentiation; Steroid hormone; Cell death; hydrogen peroxide; Myoblast; Cell differentiation; Striated muscle; Hydrogen Peroxides; In vitro; muscle cell
• ISSN: 0926-5287; 1297-9708
• DOI: 10.1051/rnd:2002018

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