Ascorbate inhibits iNOS expression in endotoxin‐ and IFNγ‐stimulated rat skeletal muscle endothelial cells

FEBS Letters

Wu, Feng¹  Tyml, Karel¹  Wilson, John X.² 

[1] Lawson Health Research Institute, University of Western Ontario, London, ON, Canada N6A 5C1;Department of Physiology, University of Western Ontario, London, ON, Canada N6A 5C1

关键词: Ascorbate;    Inducible nitric oxide synthase;    Endothelial cells;    Oxidant;    Sepsis;    NO;    nitric oxide;    iNOS;    inducible nitric oxide synthase;    ECs;    endothelial cells;    LPS;    lipopolysaccharide;    IFNγ;    interferon-γ;    L-NAME;    N-nitro-L-arginine methyl ester;    XO/X;    xanthine oxidase/xanthine;    SOD;    superoxide dismutase;   

DOI  :  10.1016/S0014-5793(02)02804-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lipopolysaccharide endotoxin and interferon-γ induced inducible nitric oxide synthase (iNOS) protein expression and nitrite/nitrate formation in microvascular endothelial cell cultures (ECs) derived from rat skeletal muscle. Pretreatment of ECs with ascorbate accumulated a large amount of ascorbate inside the cells and consequently decreased both intracellular oxidant level and iNOS induction. These effects of ascorbate were abolished in the presence of exogenous superoxide generated by xanthine oxidase/xanthine plus catalase but were not altered when N-nitro-L-arginine methyl ester was applied to inhibit nitric oxide synthesis. Ascorbate also attenuated the activation of transcription factor IRF-1 but not NFκB. These results indicate that ascorbate inhibits iNOS expression in ECs by an antioxidant mechanism independent of both NFκB activation and the reported negative feedback effect of nitric oxide.

【 授权许可】

Unknown