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.
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U2 - 10.1016/j.nbd.2004.05.003
DO - 10.1016/j.nbd.2004.05.003
M3 - Article
C2 - 15350965
AN - SCOPUS:4444284269
VL - 17
SP - 54
EP - 61
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 1
ER -