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MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress

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...

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Autores principales: Hsieh, Ya-Ching, Mounsey, Ross B., Teismann, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145900/
https://www.ncbi.nlm.nih.gov/pubmed/21667279
http://dx.doi.org/10.1007/s00210-011-0660-8
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author Hsieh, Ya-Ching
Mounsey, Ross B.
Teismann, Peter
author_facet Hsieh, Ya-Ching
Mounsey, Ross B.
Teismann, Peter
author_sort Hsieh, Ya-Ching
collection PubMed
description 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.
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spelling pubmed-31459002011-09-21 MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress Hsieh, Ya-Ching Mounsey, Ross B. Teismann, Peter Naunyn Schmiedebergs Arch Pharmacol Original Article 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. Springer-Verlag 2011-06-12 2011 /pmc/articles/PMC3145900/ /pubmed/21667279 http://dx.doi.org/10.1007/s00210-011-0660-8 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Original Article
Hsieh, Ya-Ching
Mounsey, Ross B.
Teismann, Peter
MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
title MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
title_full MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
title_fullStr MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
title_full_unstemmed MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
title_short MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress
title_sort mpp(+)-induced toxicity in the presence of dopamine is mediated by cox-2 through oxidative stress
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145900/
https://www.ncbi.nlm.nih.gov/pubmed/21667279
http://dx.doi.org/10.1007/s00210-011-0660-8
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