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

Arkadiusz Orzechowski*, Jean Grizard, Michał Jank, Barbara Gajkowska, Małgorzata Łokociejewska, Magda Zaron-Teperek, Michał Godlewski

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)

    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 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.

    Original languageEnglish
    Pages (from-to)197-216
    Number of pages20
    JournalReproduction Nutrition Development
    Volume42
    Issue number3
    Publication statusPublished - May 2002

    Keywords

    • Cell death
    • Differentiation
    • Hydrogen peroxide
    • Muscle cell

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