Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation.

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Chae SW, Bang YJ, Kim KM, Lee KY, Kang BY, Kim EM, Inoue H, Hwang O, Choi HJ

Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation.

Biochem Biophys Res Commun. 2007 Aug 3;359(3):735-41. Epub 2007 Jun 4.

PubMed ID

17560944 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Sapropterin	Prostaglandin G/H synthase 2	Protein	Humans	Unknown	Inducer	Details