Oxidative stress–associated mitochondrial dysfunction in corticosteroid-treated muscle cells

✍ Scribed by Yasushi Oshima; Yukiko Kuroda; Makoto Kunishige; Toshio Matsumoto; Takao Mitsui

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 96 KB
• Volume: 30
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/mus.20036

✦ Synopsis

Abstract

We analyzed the effects of corticosteroid on mitochondrial membrane potentials (ΔΨ~m~), generation of reactive oxygen species (ROS), and apoptosis in a human rhabdomyosarcoma cell line, RD, and a dopaminergic neuroblastoma cell line, SH‐SY5Y. The cell lines were cultured in the presence or absence of dexamethasone and superoxide dismutase (SOD) for up to 1 week. Dexamethasone treatment increased ΔΨ~m~, ROS generation, and apoptosis in proliferating RD cells. Treatment with SOD attenuated ROS generation and apoptosis, but not ΔΨ~m~. The increase in ΔΨ~m~ seemed to be the primary effect of dexamethasone on proliferating RD cells, which is probably mediated by mitochondrial transcription. In differentiated RD cells, but not differentiated SH‐SY5Y cells, dexamethasone treatment showed a delayed effect of interfering with the ΔΨ~m~ and increasing ROS generation and apoptosis. Since these changes disappeared in the presence of SOD, dexamethasone primarily induced ROS generation, resulting in apoptosis. We speculate that this mechanism provides the basis of a pathophysiological model of corticosteroid myopathy. Muscle Nerve 30:49–54,2004