Ishii Masakazu, Shimizu Shunichi, Wajima Teruaki, Hagiwara Tamio, Negoro Takaharu, Miyazaki Akira, Tobe Takashi, Kiuchi Yuji
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
J Pharmacol Sci. 2005 Feb;97(2):299-302. doi: 10.1254/jphs.sc0040146. Epub 2005 Feb 5.
We examined the effect of H(2)O(2) on the expression of GTP cyclohydrolase I (GTPCH) feedback regulating protein (GFRP). Addition of H(2)O(2) to endothelial cells decreased GFRP mRNA levels, in contrast to the increase of tetrahydrobiopterin (BH(4)) content and GTPCH mRNA levels. The inhibitors of nitric oxide (NO) synthase and GTPCH had no influence on the decrease of GFRP mRNA levels in H(2)O(2)-treated cells. It is suggested that H(2)O(2) induces BH(4) synthesis through not only induction of GTPCH but also reduction of GFRP. The decrease of GFRP mRNA level appears to be independent of the produced NO and BH(4).
我们研究了过氧化氢（H₂O₂）对GTP环化水解酶I（GTPCH）反馈调节蛋白（GFRP）表达的影响。与四氢生物蝶呤（BH₄）含量和GTPCH mRNA水平升高相反，向内皮细胞中添加H₂O₂会降低GFRP mRNA水平。一氧化氮（NO）合酶抑制剂和GTPCH对H₂O₂处理细胞中GFRP mRNA水平的降低没有影响。提示H₂O₂不仅通过诱导GTPCH，还通过降低GFRP来诱导BH₄合成。GFRP mRNA水平的降低似乎与产生的NO和BH₄无关。
