Ca2+-induced oxidative stress in brain mitochondria treated with the respiratory chain inhibitor rotenone.
In this study we show that micromolar Ca(2+) concentrations (>10 microM) strongly stimulate the release of reactive oxygen species (ROS) in rotenone-treated isolated rat forebrain mitochondria. Ca(2+)-stimulated mitochondrial ROS release was associated with membrane lipid peroxidation and was directly correlated with the degree of complex I inhibition by rotenone. On the other hand, Ca(2+) did not increase mitochondrial ROS release in the presence of the complex I inhibitor 1-methyl-4-phenylpyridinium. Cyclosporin A had no effect on Ca(2+)-stimulated mitochondrial ROS release in the presence of rotenone, indicating that mitochondrial permeability transition is not involved in this process. We hypothesized that Ca(2+)-induced mitochondrial oxidative stress associated with partial inhibition of complex I may be an important factor in neuronal cell death observed in the neurodegenerative disorder Parkinson's disease.
Sousa
Solange C
SC
Departamento de Patologia Cli;nica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP 13083-970, Campinas, Brazil.
Maciel
Evelise N
EN
Vercesi
Anibal E
AE
Castilho
Roger F
RF
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D004357:Drug Synergism; D004579:Electron Transport / Q000187:drug effects; D005260:Female; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D012402:Rotenone; D002118:Calcium