S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Cancer Biology (협동과정-종양생물학전공) Journal Papers (저널논문_협동과정-종양생물학전공)
Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation
- 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
- Biochem Biophys Res Commun. 2007 Aug 3;359(3):735-41. Epub 2007 Jun 4.
- Animals; Biopterin/*analogs & derivatives/pharmacology; Cells, Cultured; Cyclooxygenase 2/genetics/*metabolism; Dopamine/*metabolism; Enzyme Activation/drug effects; Gene Expression Regulation, Enzymologic; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; Mesencephalon/drug effects/enzymology; Neurons/drug effects/enzymology; Oxidation-Reduction/drug effects; Oxidative Stress/drug effects; Rats; Signal Transduction; Transcription Factor AP-1/genetics/metabolism; Transcription, Genetic/genetics; Up-Regulation
- 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.
- 0006-291X (Print)
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