Reduction of GTP cyclohydrolase I feedback regulating protein expression by hydrogen peroxide in vascular endothelial cells.
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).
Ishii
Masakazu
M
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. masakazu@pharm-u.ac.jp
Shimizu
Shunichi
S
Wajima
Teruaki
T
Hagiwara
Tamio
T
Negoro
Takaharu
T
Miyazaki
Akira
A
Tobe
Takashi
T
Kiuchi
Yuji
Y
D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006136:GTP Cyclohydrolase / Q000037:antagonists & inhibitors* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
C101092:GCHFR protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D006861:Hydrogen Peroxide; D006136:GTP Cyclohydrolase