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

Hsiao Sui Lo, HsuehCheng Chinag, Anya M Y Lin, Han Yun Chiang, Yeh Chiu Chu, Lung Sen Kao

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)54-61
Number of pages8
JournalNeurobiology of Disease
Volume17
Issue number1
DOIs
Publication statusPublished - 2004 Oct 1

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PC12 Cells
Parkinson Disease
Dopamine
Cell Death
Dopaminergic Neurons
Corpus Striatum
Calcium Channel Blockers
Substantia Nigra
Sulfhydryl Compounds
Necrosis
Antioxidants
Apoptosis

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

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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.",
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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. / Lo, Hsiao Sui; Chinag, HsuehCheng; Lin, Anya M Y; Chiang, Han Yun; Chu, Yeh Chiu; Kao, Lung Sen.

In: Neurobiology of Disease, Vol. 17, No. 1, 01.10.2004, p. 54-61.

Research output: Contribution to journalArticle

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