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Ca2+-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I.
- Source :
- Journal of Neurochemistry; May2005, Vol. 93 Issue 3, p526-537, 12p
- Publication Year :
- 2005
-
Abstract
- Mitochondrial complex I dysfunction has been implicated in a number of brain pathologies, putatively owing to an increased rate of reactive oxygen species (ROS) release. However, the mechanisms regulating the ROS burden are poorly understood. In this study we investigated the effect of Ca<superscript>2+</superscript> loads on ROS release from rat brain mitochondria with complex I partially inhibited by rotenone. The addition of 20 nmrotenone to brain mitochondria increased ROS release. Ca<superscript>2+</superscript> (100 µm) alone had no effect on ROS release, but greatly potentiated the effects of rotenone. The effect of Ca<superscript>2+</superscript> was decreased by ruthenium red. Ca<superscript>2+</superscript>-challenged mitochondria lose about 88% of their glutathione and 46% of their cytochromecunder these conditions, although this depends only on Ca<superscript>2+</superscript> loading and not complex I inhibition. ADP in combination with oligomycin decreased the loss of glutathione and cytochromecand free radical generation. Cyclosporin A alone was ineffective in preventing these effects, but augmented the protection provided by ADP and oligomycin. Non-specific permeabilization of mitochondria with alamethicin also increased the ROS signal, but only when combined with partial inhibition of complex I. These results demonstrate that Ca<superscript>2+</superscript> can greatly increase ROS release by brain mitochondria when complex I is impaired. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 93
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16730825
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2005.03042.x