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Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q 10
Author(s) -
Moon Younghye,
Lee Kun Ho,
Park JuneHee,
Geum Dongho,
Kim Kyungjin
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03112.x
Subject(s) - rotenone , depolarization , dopaminergic , membrane potential , biology , neurodegeneration , mitochondrion , programmed cell death , neurotoxicity , microbiology and biotechnology , chemistry , biochemistry , biophysics , apoptosis , dopamine , neuroscience , medicine , toxicity , disease , organic chemistry
Chronic exposure to the pesticide rotenone induces a selective degeneration of nigrostriatal dopaminergic neurons and reproduces the features of Parkinson's disease in experimental animals. This action is thought to be relevant to its inhibition of the mitochondrial complex I, but the precise mechanism of this suppression in selective neuronal death is still elusive. Here we investigate the mechanism of dopaminergic neuronal death mediated by rotenone in primary rat mesencephalic neurons. Low concentrations of rotenone (5–10 n m ) induce the selective death of dopaminergic neurons without significant toxic effects on other mesencephalic cells. This cell death was coincident with apoptotic events including capsase‐3 activation, DNA fragmentation, and mitochondrial membrane depolarization. Pretreatment with coenzyme Q 10 , the electron transporter in the mitochondrial respiratory chain, remarkably reduced apoptosis as well as the mitochondrial depolarization induced by rotenone, but other free radical scavengers such as N ‐acetylcysteine, glutathione, and vitamin C did not. Furthermore, the selective neurotoxicity of rotenone was mimicked by the mitochondrial protonophore carbonyl cyanide 4‐(trifluoromethoxy) phenylhydrazone (FCCP), a cyanide analog that effectively collapses a mitochondrial membrane potential. These data suggest that mitochondrial depolarization may play a crucial role in rotenone‐induced selective apoptosis in rat primary dopaminergic neurons.