1P287 Effects of reactive oxygen specles on tetrahydrobiopterin content in vascular endothelial cells

Tetrahydrobiopterin (BH4) is not only one of the cofactors of nitric oxide synthase, but also has a protective effect against nitric oxide and/or reactive oxygen species (ROS). We previously shown that hydrogen peroxide, one of the ROS, increased total biopterin (BH4 + BH2 + biopterin) content throu...

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Published in:Journal of Pharmacological Sciences 2003, Vol.91 (suppl.1), p.159-159
Main Authors: Yoshiyuki Miyasaka, Shunichi Shimizu, Rika Shinmoto, Masakazu Ishii, Yuji Kiuchi
Format: Article
Language:Japanese
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Summary:Tetrahydrobiopterin (BH4) is not only one of the cofactors of nitric oxide synthase, but also has a protective effect against nitric oxide and/or reactive oxygen species (ROS). We previously shown that hydrogen peroxide, one of the ROS, increased total biopterin (BH4 + BH2 + biopterin) content through the induction of GTP-cyclohydrolase I (GTPCH) in vascular endothelial cells. The aim of this study was to characterize the effect of hydrogen peroxide on BH4 content, but not its oxidized forms, by compared to other ROS in bovine aortic endothelial cells (BAECS). In a cell-free assay system, peroxynitrite but not hydrogen peroxide immediately destroyed BH4. Addition of hydrogen peroxide to BAECS increased BH4 content, and the hydrogen peroxide-induced increase in BH4 content was inhibited by catalase, but not by superoxide dismutase and hydroxyl radical scavengers. Moreover, peroxynitrite and superoxide markedly decreased BH4 content. These results strongly suggested that hydrogen peroxide stimulates BH4 synthesis through the induction of GTPCH in vascular endothelial cells. Hydrogen peroxide appears to be one of the important signaling molecules to stimulate BH4 synthesis.
ISSN:1347-8613