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 language | English |
|---|---|
| Pages (from-to) | 54-61 |
| Number of pages | 8 |
| Journal | Neurobiology of Disease |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2004 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Neurology
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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 journal › Article
TY - JOUR
T1 - Synergistic effects of dopamine and Zn 2+ on the induction of PC12 cell death and dopamine depletion in the striatum
T2 - Possible implication in the pathogenesis of Parkinson's disease
AU - Lo, Hsiao Sui
AU - Chinag, HsuehCheng
AU - Lin, Anya M Y
AU - Chiang, Han Yun
AU - Chu, Yeh Chiu
AU - Kao, Lung Sen
PY - 2004/10/1
Y1 - 2004/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=4444284269&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4444284269&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2004.05.003
DO - 10.1016/j.nbd.2004.05.003
M3 - Article
VL - 17
SP - 54
EP - 61
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 1
ER -