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Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10.
J Neurochem. 2005 Jun; 93(5):1199-208.JN

Abstract

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 nM) 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 Q10, 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.

Authors+Show Affiliations

Interdisciplinary Program in Neurosciences, Seoul National University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15934940

Citation

Moon, Younghye, et al. "Mitochondrial Membrane Depolarization and the Selective Death of Dopaminergic Neurons By Rotenone: Protective Effect of Coenzyme Q10." Journal of Neurochemistry, vol. 93, no. 5, 2005, pp. 1199-208.
Moon Y, Lee KH, Park JH, et al. Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. J Neurochem. 2005;93(5):1199-208.
Moon, Y., Lee, K. H., Park, J. H., Geum, D., & Kim, K. (2005). Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. Journal of Neurochemistry, 93(5), 1199-208.
Moon Y, et al. Mitochondrial Membrane Depolarization and the Selective Death of Dopaminergic Neurons By Rotenone: Protective Effect of Coenzyme Q10. J Neurochem. 2005;93(5):1199-208. PubMed PMID: 15934940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. AU - Moon,Younghye, AU - Lee,Kun Ho, AU - Park,June-Hee, AU - Geum,Dongho, AU - Kim,Kyungjin, PY - 2005/6/7/pubmed PY - 2005/6/25/medline PY - 2005/6/7/entrez SP - 1199 EP - 208 JF - Journal of neurochemistry JO - J. Neurochem. VL - 93 IS - 5 N2 - 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 nM) 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 Q10, 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. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15934940/Mitochondrial_membrane_depolarization_and_the_selective_death_of_dopaminergic_neurons_by_rotenone:_protective_effect_of_coenzyme_Q10_ L2 - https://doi.org/10.1111/j.1471-4159.2005.03112.x DB - PRIME DP - Unbound Medicine ER -