Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10.

摘要: Chronic exposure to the pesticide rotenone induces a selective degeneration of nigrostriatal dopaminergic neurons and reproduces features Parkinson's disease in experimental animals. This action is thought be relevant its inhibition mitochondrial complex I, but precise mechanism this suppression neuronal death still elusive. Here we investigate mediated by primary rat mesencephalic neurons. Low concentrations (5-10 nM) induce without significant toxic effects on other cells. cell was coincident with apoptotic events including capsase-3 activation, DNA fragmentation, membrane depolarization. Pretreatment coenzyme Q10, electron transporter respiratory chain, remarkably reduced apoptosis as well depolarization induced rotenone, free radical scavengers such N-acetylcysteine, glutathione, vitamin C did not. Furthermore, neurotoxicity mimicked protonophore carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), analog that effectively collapses potential. These data suggest may play crucial role rotenone-induced