Role of Cyclooxygenase-2 in Tetrahydrobiopterin-induced Dopamine Oxidation.
From: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, South Korea.
Biochemical and biophysical research communications
- Publish Date: Aug 2007
- ISSN: 0006-291X
- Volume: 359
- Issue: 3
- Pages: 735-41
- Medium: Print
- Language: English
- Citation (JAMA): Chae Sung-Wook, Bang Yeo Jin, Kim Kyeong-Man, et al. Role of Cyclooxygenase-2 in Tetrahydrobiopterin-induced Dopamine Oxidation.. Biochem. Biophys. Res. Commun. Aug 2007;359:735-41
Abstract
Dopamine is considered one of the main contributing factors in the induction of oxidative stress and selective dopaminergic neurodegeneration in Parkinson’s disease. We have previously reported that tetrahydrobiopterin (BH4) leads to dopamine oxidation and renders dopamine-producing cells vulnerable. In the present study, we found that BH4 selectively upregulates cyclooxygenase-2 (COX-2) expression in dopaminergic cells. BH4 caused an induction of COX-2 mRNA, and a critical regulatory motif for BH4-induced transcriptional activation of COX-2 is CRE/AP-1. COX-2 can oxidize dopamine and cause oxidative stress, which is evidenced by the findings that significant increase in dopamine-chrome formation and protein carbonyl contents by BH4-induced COX-2 up-regulation, and the increases are abolished by COX-2 selective inhibitor meloxicam. Increased COX-2 promotes dopaminergic neurodegeneration in both SH-SY5Y cells and rat mesencephalic neurons. These data suggest that BH4-induced COX-2 expression is responsible for dopamine oxidation, leading to the preferential vulnerability of dopaminergic cells in Parkinson’s disease.
Mesh Headings (Keywords): Animals, Biopterin, Cells, Cultured, Cyclooxygenase 2, Dopamine, Enzyme Activation, Gene Expression Regulation, Enzymologic, Humans, JNK Mitogen-Activated Protein Kinases, Mesencephalon, Neurons, Oxidation-Reduction, Oxidative Stress, Rats, Signal Transduction, Transcription Factor AP-1, Transcription, Genetic, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17560944
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