Inhibitory effect of neopterin on NADPH‐dependent superoxide‐generating oxidase of rat peritoneal macrophages

FEBS Letters

Kojima, Shuji¹  Icho, Takeshi¹  Kitabatake, Katsuaki²  Nomura, Takafumi¹  Kubota, Kazuhiko¹  Kajiwara, Yoshio² 

[1] Research Institute for Biosciences, Science University of Tokyo, 2669 Yamazaki, Nodashi, Chiba 278, Japan;Applied Technology Research Laboratory, Asahi Breweries, Ltd., 2-13-1 Ohmorikita, Ohtaku, Tokyo 143, Japan

关键词: Neopterin;    Antioxidant;    Superoxide;    NADPH-oxidase;    NP;    neopterin;    NPH4;    5;    6;    7;    8-tetrahydroneopterin;    NPH2;    7;    8-dihydroneopterin;    NPH2TP;    7;    8-dihydroneopterin triposphate;    GTP;    guanosine triphosphate;    BP;    biopterin;    BPH4;    5;    6;    7;    8-tetrahydrobiopterin;    IFN-γ;    interferon-γ;    PMA;    phorbol myristate acetate;    X/XOD;    xanthine/xanthine oxidase;    PK.C;    protein kinase C;    SDS;    sodium dodecyl sulfate;    SOD;    Superoxide dismutase;    FAD;    flavin adenine dinucleiotide;   

DOI  :  10.1016/0014-5793(93)80207-B

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effect of the oxidized form of neopterin (NP) on the NADPH-dependent superoxide-generating oxidase (NADPH-oxidase) was investigated in both whole-cell and cell-free activation systems by using peritoneal macrophages of rats which had received an intraperitoneal injection of mineral oil. In the whole-cell system, NP remarkably inhibited the generation of Superoxides in macrophages stimulated with phorbol myristate acetate (PMA). NP also showed an significant suppression of the activation of superoxide-generating NADPH-oxidase in the cell-free system using solubilized membranes and sodium dodecyl sulfate (SDS) as a stimulant. The 50%-inhibitory concentration (IC₅₀) of NP was about 1 μM in both assay systems. In a kinetic study, competitive inhibition of the NADPH-oxidase by NP was observed in the cell-free system with a calculated inhibition constant (K _i) of 6.50 μM. These findings suggest that NP may play an important role in the suppression of Superoxide generation via the inhibition of the NADPH-oxidase in phagocytes.

【 授权许可】

Unknown