MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress.
Naunyn Schmiedebergs Arch Pharmacol
; 384(2): 157-67, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21667279
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_parkinson_disease
Asunto principal:
Dopamina
/
1-Metil-4-fenilpiridinio
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Estrés Oxidativo
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Ciclooxigenasa 2
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Neuronas Dopaminérgicas
Límite:
Animals
Idioma:
En
Revista:
Naunyn Schmiedebergs Arch Pharmacol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido