@article{41ef5569bf5640718a215f1be54ade9a,
title = "Synergistic effects of dopamine and Zn 2+ 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 2O 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.",
keywords = "[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide], Cell death, DMEM, Dopamine, Dulbecco's modified Eagle's medium, MTT, Parkinson's disease, PBS, PC12 cell, PD, phosphate-buffered saline, TH, TSQ, tyrosine hydroxylase, Zinc",
author = "Lo, {Hsiao Sui} and Chiang, {Hsueh Cheng} and Lin, {Anya M.Y.} and Chiang, {Han Yun} and Chu, {Yeh Chiu} and Kao, {Lung Sen}",
note = "Funding Information: We thank Drs. E.W. Westhead and M.J. Fann for their critical comments on the manuscript, Dr. Fu-Chin Liu for his help with TH staining of brain slices, and Ms. Huei-Jen Min for the preparation of cells. This study was supported by grants from National Science Council (NSC87-2314-B001-038 and NSC88-2314-B001-041), Taipei, Taiwan, R.O.C. and VTY Joint Research Program, Tsou's Foundation (VTY90-P5-39 and VTY92-P5-31), Taiwan, R.O.C.",
year = "2004",
month = oct,
doi = "10.1016/j.nbd.2004.05.003",
language = "English",
volume = "17",
pages = "54--61",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "1",
}