GTP cyclohydrolase I mRNA induction and tetrahydrobiopterin synthesis in human endothelial cells.
The key role of tetrahydrobiopterin (BH4) in the synthesis of nitric oxide by human umbilical vein endothelial cells (HUVEC) has been demonstrated. We characterized the induction of BH4 synthesis in a cell line (ECV) derived from HUVEC and primary HUVEC. A significant induction of guanosine triphosphate cyclohydrolase I (GTPCH) mRNA was observed in response to TNF, IL-1beta, and IFNgamma in ECV and HUVEC. The induction of GTPCH mRNA was abolished by actinomycin D. The cytokines led to an increased accumulation of BH4 in ECV. This effect was prevented by 2,4-diamino-6-hydroxypyrimidine, a selective inhibitor of GTPCH, as well as by actinomycin D and by cycloheximide. Results provide evidence for an increase in GTPCH activity and in BH4 levels in response to immunostimulants in human endothelial cells.
Hattori
Y
Y
Department of Endocrinology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Nakanishi
N
N
Kasai
K
K
Shimoda
S I
SI
D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology; D004790:Enzyme Induction; D006136:GTP Cyclohydrolase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007042:Hypoxanthines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*
D016207:Cytokines; D007042:Hypoxanthines; D012333:RNA, Messenger; D003609:Dactinomycin; D001708:Biopterins; D003907:Dexamethasone; D003513:Cycloheximide; D006136:GTP Cyclohydrolase; C017202:2,4-diaminohypoxanthine; C003402:sapropterin