Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation

被引:15
作者
Chae, Sung-Wook
Bang, Yeo Jin
Kim, Kyeong-Man
Lee, Kwang Youl
Kan, Bok Yun
Kim, Eun Mee
Inoue, Hiroyasu
Hwang, Onyou
Choi, Hyun Jin [1 ]
机构
[1] Chonnam Natl Univ, Coll Pharm, Kwangju 500757, South Korea
[2] Chonnam Natl Univ, Res Inst Drug Dev, Kwangju 500757, South Korea
[3] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul 138736, South Korea
[4] Nara Womens Univ, Dept Food Sci & Nutr, Nara 630, Japan
基金
新加坡国家研究基金会;
关键词
cyclooxygenase-2 (COX-2); dopamine; oxidative stress; tetrahydrobiopterin (BH4); Parkinson's disease;
D O I
10.1016/j.bbrc.2007.05.190
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:735 / 741
页数:7
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