2,4‐diamino‐6‐hydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis, downregulates the expression of iNOS protein and mRNA in primary murine macrophages

FEBS Letters

Rbllinghoff, Martin¹  Bogdan, Christian¹  Stenger, Steffen¹  Werner-Felmayer, Gabriele²  Wachter, Helmut²  Werner, Ernst² 

[1] Institute for Clinical Microbiology and Immunology, University of Erlangen, Friedrich-Alexander-Universität, Wasserturmstraße 3, D-91054 Erlangen, Germany;Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria

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;   

DOI  :  10.1016/0014-5793(95)00284-G

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown