2,4‐diamino‐6‐hydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis, downregulates the expression of iNOS protein and mRNA in primary murine macrophages
[摘要] 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, blocks the synthesis of tetrahydrobiopterin (BH4), which is a known cofactor of inducible nitric oxide synthase (iNOS). Previously, DAHP was shown to suppress the production of nitric oxide by cytokine-activated fibroblasts, smooth muscle cells or endothelial cells which could be attributed to its function as a cofactor antagonist. Here, we demonstrate that in interferon-γ-activated murine peritoneal macrophages DAHP suppresses the expression of iNOS mRNA and protein in a BH4-independent manner and, thus, acts by a novel mechanism.
[发布日期] [发布机构]
[效力级别] [学科分类] 生物化学/生物物理
[关键词] 2;4-Diamino-6-hydroxy-pyrimidine;Inducible nitric oxide synthase;Nitric oxide;Tetrahydrobiopterin;GTP cyclohydrolase I;(BH4);2-amino-4-hydroxy-6-(l;-erythro-1;2-dihydroxy-propyl)-5;6;7;8-tetrahydropteridin;DAHP;2;4-diamino-6-hydroxy-pyrimidine;iNOS;inducible nitric oxide synthase (NOS whose activity is independent of exogenous calmodulin and elevation of intracellular [Ca2+] above the level in resting cells;IFN-γ;interferon-γ;LPS;bacterial lipopolysaccharide;MTT;3-[4;5-dimethylthiazol-2-yl]-2;5-diphenyl tetrazolium bromide;NO;nitric oxide;l-Sep;l-sepiapterin;TGF-β;transforming growth factor-β [时效性]
