Oxidative stress-associated mitochondrial dysfunction in corticosteroid-treated muscle cells.
We analyzed the effects of corticosteroid on mitochondrial membrane potentials (DeltaPsi(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 DeltaPsi(m), ROS generation, and apoptosis in proliferating RD cells. Treatment with SOD attenuated ROS generation and apoptosis, but not DeltaPsi(m). The increase in DeltaPsi(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 DeltaPsi(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.
Oshima
Yasushi
Y
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Kuroda
Yukiko
Y
Kunishige
Makoto
M
Matsumoto
Toshio
T
Mitsui
Takao
T
D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000378:metabolism*; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D009447:Neuroblastoma; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012208:Rhabdomyosarcoma
D005938:Glucocorticoids; D017382:Reactive Oxygen Species; D003907:Dexamethasone