دورية أكاديمية
MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress.
العنوان: | MPP(+)-induced toxicity in the presence of dopamine is mediated by COX-2 through oxidative stress. |
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المؤلفون: | Hsieh YC; School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Aberdeen, Scotland, UK., Mounsey RB, Teismann P |
المصدر: | Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2011 Aug; Vol. 384 (2), pp. 157-67. Date of Electronic Publication: 2011 Jun 12. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Berlin, New York, Springer Verlag. |
مواضيع طبية MeSH: | 1-Methyl-4-phenylpyridinium/*toxicity , Cyclooxygenase 2/*metabolism , Dopamine/*metabolism , Dopaminergic Neurons/*drug effects , Oxidative Stress/*drug effects, Animals ; Apoptosis/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Cyclooxygenase 2 Inhibitors/pharmacology ; Dopamine/pharmacology ; Dopaminergic Neurons/enzymology ; Dopaminergic Neurons/metabolism ; Immunohistochemistry ; Mesencephalon/cytology ; Mesencephalon/embryology ; Mesencephalon/metabolism ; Parkinson Disease/enzymology ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism |
مستخلص: | 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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معلومات مُعتمدة: | United Kingdom WT_ Wellcome Trust |
المشرفين على المادة: | 0 (Cyclooxygenase 2 Inhibitors) 0 (Reactive Oxygen Species) EC 1.14.99.1 (Cyclooxygenase 2) R865A5OY8J (1-Methyl-4-phenylpyridinium) VTD58H1Z2X (Dopamine) |
تواريخ الأحداث: | Date Created: 20110614 Date Completed: 20111212 Latest Revision: 20211020 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC3145900 |
DOI: | 10.1007/s00210-011-0660-8 |
PMID: | 21667279 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1432-1912 |
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DOI: | 10.1007/s00210-011-0660-8 |