Abstract
Accumulating evidence suggests that endogenous dopamine may act as a neurotoxin and thereby participate in the pathophysiology of Parkinson's disease (PD). Cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of PD due to its ability to generate reactive oxygen species (ROS). Inhibition of COX-2 leads to neuroprotection by preventing the formation of dopamine-quinone. In this study, we examined whether dopamine mediates 1-methyl-4-phenylpyridinium (MPP(+))-induced toxicity in primary ventral mesencephalic (VM) neurons, an in vitro model of PD, and if so, whether the protective effects of COX-2 inhibitors on dopamine mediated MPP(+)-induced VM neurotoxicity and VM dopaminergic cell apoptosis result from the reduction of ROS. Reserpine, a dopamine-depleting agent, significantly reduced VM neurotoxicity induced by MPP(+), whereas dopamine had an additive effect on MPP(+)-induced VM neurotoxicity and VM dopaminergic cell apoptosis. However, inhibition of COX-2 by a selective COX-2 inhibitor (DFU) or ibuprofen significantly attenuated MPP(+)-induced VM cell toxicity and VM dopaminergic cell apoptosis, which was accompanied by a decrease in ROS production in VM dopaminergic neurons. These results suggest that dopamine itself mediates MPP(+)-induced VM neurotoxicity and VM dopaminergic cell apoptosis in the presence of COX-2.
Original language | English |
---|---|
Pages (from-to) | 157-167 |
Number of pages | 11 |
Journal | Naunyn-Schmiedeberg's Archives of Pharmacology |
Volume | 384 |
Issue number | 2 |
Early online date | 12 Jun 2011 |
DOIs | |
Publication status | Published - Aug 2011 |
Keywords
- 1-Methyl-4-phenylpyridinium
- Animals
- Apoptosis
- Cell Survival
- Cells, Cultured
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Dopamine
- Dopaminergic Neurons
- Immunohistochemistry
- Mesencephalon
- Oxidative Stress
- Parkinson Disease
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species