title: Synergistic effects of dopamine and Zn2+ on the induction of PC12 cell death and dopamine depletion in the striatum: possible implication in the pathogenesis of Parkinson's disease.
abstract: The mechanism that underlies the progressive degeneration of the dopaminergic neurons in Parkinson's disease (PD) is not clear. The Zn(2+) level in the substantia nigra of Parkinson's patients is increased. However, it is unknown whether Zn(2+) has a role in the degeneration of dopaminergic neurons. This study identifies an interaction between dopamine and Zn(2+) that induces cell death. When PC12 cells were pretreated with Zn(2+) before dopamine treatment, dopamine and Zn(2+) synergistically increased cell death, while Zn(2+) and H(2)O(2) had only additive effects on cell death. The synergistic effect appeared to be caused by increased apoptosis rather than necrosis. The synergistic effect was specific for Zn(2+). The synergistic effect was inhibited by thiol antioxidants but was not significantly affected by calcium channel blockers. There is a similar synergistic effect when dopamine and Zn(2+) were coinfused into the striatum, resulting in striatal dopamine content depletion in vivo. Thus, both dopamine oxidation and Zn(2+) are possibly linked to the degeneration of dopaminergic neurons.
authors.affiliation: Department of Neurology, Taiwan Adventist Hospital, Taipei, Taiwan, ROC.
authors.forename: Hsiao-Sui
authors.initials: HS
authors.lastname: Lo
authors.forename: Hsueh-Cheng
authors.initials: HC
authors.lastname: Chiang
authors.forename: Anya M Y
authors.initials: AM
authors.lastname: Lin
authors.forename: Han-Yun
authors.initials: HY
authors.lastname: Chiang
authors.forename: Yeh-Chiu
authors.initials: YC
authors.lastname: Chu
authors.forename: Lung-Sen
authors.initials: LS
authors.lastname: Kao
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D016716:PC12 Cells; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000494:pharmacology*
chemical_list: D015032:Zinc; D004298:Dopamine