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, Hsueh Cheng Chiang, Anya M.Y. Lin, Han Yun Chiang, Yeh Chiu Chu, Lung Sen Kao

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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
StatePublished - Oct 2004

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

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