Oxidative stress-associated mitochondrial dysfunction in corticosteroid-treated muscle cells
Yasushi Oshima1, Yukiko Kuroda, Makoto Kunishige
1Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Abstract:
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.
Insights
Corticosteroids like dexamethasone increase mitochondrial damage and cell death in muscle cells by raising mitochondrial membrane potential and reactive oxygen species (ROS). Superoxide dismutase (SOD) partially counteracted these effects, suggesting a role for ROS in corticosteroid-induced apoptosis.
Area of Science:
- Cell Biology
- Mitochondrial Physiology
- Pharmacology
Background:
- Corticosteroids are widely used but can cause myopathy.
- Mitochondrial dysfunction is implicated in various pathologies.
- Understanding corticosteroid effects on mitochondria is crucial.
Purpose of the Study:
- To investigate the impact of dexamethasone on mitochondrial membrane potential (DeltaPsi(m)), reactive oxygen species (ROS) generation, and apoptosis.
- To explore the role of ROS in dexamethasone-induced cellular changes.
- To examine these effects in proliferating and differentiated human cell lines (RD and SH-SY5Y).
Main Methods:
- Cell culture of RD (rhabdomyosarcoma) and SH-SY5Y (neuroblastoma) lines.
- Treatment with dexamethasone and superoxide dismutase (SOD).
- Assessment of DeltaPsi(m), ROS levels, and apoptosis over one week.
Main Results:
- Dexamethasone increased DeltaPsi(m), ROS, and apoptosis in proliferating RD cells.
- SOD attenuated ROS and apoptosis but not DeltaPsi(m) in proliferating RD cells.
- Dexamethasone induced delayed mitochondrial dysfunction, ROS, and apoptosis in differentiated RD cells, effects abolished by SOD.
Conclusions:
- Dexamethasone's primary effect on proliferating RD cells involves increasing DeltaPsi(m), potentially via mitochondrial transcription.
- In differentiated RD cells, dexamethasone primarily induces ROS generation, leading to apoptosis.
- These findings suggest a pathophysiological model for corticosteroid myopathy.
