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Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation

Cited 16 time in Web of Science Cited 15 time in Scopus
Authors
Chae, Sung-Wook; Bang, Yeo Jin; Kim, Kyeong-Man; Lee, Kwang Youl; Kang, Bok Yun; Kim, Eun Mee; Inoue, Hiroyasu; Hwang, Onyou; Choi, Hyun Jin
Issue Date
2007-06-15
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 2007 Aug 3;359(3):735-41. Epub 2007 Jun 4.
Keywords
AnimalsBiopterin/*analogs & derivatives/pharmacologyCells, CulturedCyclooxygenase 2/genetics/*metabolismDopamine/*metabolismEnzyme Activation/drug effectsGene Expression Regulation, EnzymologicHumansJNK Mitogen-Activated Protein Kinases/metabolismMesencephalon/drug effects/enzymologyNeurons/drug effects/enzymologyOxidation-Reduction/drug effectsOxidative Stress/drug effectsRatsSignal TransductionTranscription Factor AP-1/genetics/metabolismTranscription, Genetic/geneticsUp-Regulation
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.
ISSN
0006-291X (Print)
Language
English
URI
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WBK-4NWMWX8-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=42cc4ae96e1cee18d2d4343cd79c7279

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17560944

https://hdl.handle.net/10371/24794
DOI
https://doi.org/10.1016/j.bbrc.2007.05.190
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
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