Reprod. Nutr. Dev. 42 (2002) 197-216
DOI: 10.1051/rnd:2002018

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

Arkadiusz Orzechowski^a, Jean Grizard^b, MichalJank^a, Barbara Gajkowska^c, Malgorzata Lokociejewska^a, Magda Zaron-Teperek^a and MichalGodlewskia<sup>a

a</sup>  Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw, Poland
^b  Unité de Nutrition et Métabolisme Protéique, Centre de Clermont-Ferrand-Theix, Institut National de la Recherche Agronomique, 63122 Saint-Genès-Champanelle, France
^c  Laboratory of Cell Ultrastructure, M. R. C. Polish Academy of Sciences, Warsaw, Poland

(Received 23 November 2001; accepted 16 May 2002)

Abstract
The hypothetical involvement of H ₂O 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 ₂O ₂. Micromolar concentrations of H ₂O ₂ 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 H ₂O ₂ 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 H ₂O ₂ directly influences myogenesis and muscle cell elimination. Moreover, H ₂O ₂ can be considered as the potent mediator of glucocorticoid-dependent effects on muscle cells.

Key words: muscle cell / hydrogen peroxide / differentiation / cell death

Correspondence and reprints: Arkadiusz Orzechowski
    e-mail: orzechowski@alpha.sggw.waw.pl

© INRA, EDP Sciences 2002