Synergistic effects of dopamine and Zn on the induction of PC12 cell death and dopamine depletion in the striatum: possible implication in the pathogenesis of Parkinson's disease

• Published in: Neurobiology of disease 2004-10, Vol.17 (1), p.54-61
• Main Authors: Lo, Hsiao-Sui, Chiang, Hsueh-Cheng, Lin, Anya M Y, Chiang, Han-Yun, Chu, Yeh-Chiu, Kao, Lung-Sen
• Format: Article
• Language: English
• ISSN: 0969-9961
• DOI: 10.1016/j.nbd.2004.05.003

The mechanism that underlies the progressive degeneration of the dopaminergic neurons in Parkinson's disease (PD) is not clear. The Zn2+ level in the substantia nigra of Parkinson's patients is increased. However, it is unknown whether Zn2+ has a role in the degeneration of dopaminergic neurons. This study identifies an interaction between dopamine and Zn2+ that induces cell death. When PC12 cells were pretreated with Zn2+ before dopamine treatment, dopamine and Zn2+ synergistically increased cell death, while Zn2+ and H2O2 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 Zn2+. 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 Zn2+ were coinfused into the striatum, resulting in striatal dopamine content depletion in vivo. Thus, both dopamine oxidation and Zn2+ are possibly linked to the degeneration of dopaminergic neurons.