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

• Published in: Muscle & nerve 2004-07, Vol.30 (1), p.49-54
• Main Authors: Oshima, Yasushi, Kuroda, Yukiko, Kunishige, Makoto, Matsumoto, Toshio, Mitsui, Takao
• Format: Article
• Language: English
• Subjects: apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Differentiation; Cell Line, Tumor; corticosteroid myopathy; dexamethasone; Dexamethasone - pharmacology; Diseases of striated muscles. Neuromuscular diseases; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Glucocorticoids - pharmacology; Humans; In Vitro Techniques; Medical sciences; Mitochondrial Diseases - chemically induced; Mitochondrial Diseases - metabolism; mitochondrial membrane potentials; Muscle Cells - drug effects; Muscle Cells - metabolism; Neuroblastoma; Neurology; Oxidative Stress; reactive oxygen species; Reactive Oxygen Species - metabolism; Rhabdomyosarcoma; Striated muscle. Tendons; superoxide dismutase; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.20036

We analyzed the effects of corticosteroid on mitochondrial membrane potentials (ΔΨm), 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 ΔΨm, ROS generation, and apoptosis in proliferating RD cells. Treatment with SOD attenuated ROS generation and apoptosis, but not ΔΨm. The increase in ΔΨm 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 ΔΨm 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