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Ascorbate inhibits iNOS expression in endotoxin‐ and IFNγ‐stimulated rat skeletal muscle endothelial cells
Author(s) -
Wu Feng,
Tyml Karel,
Wilson John X.
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02804-1
Subject(s) - nitric oxide , xanthine oxidase , chemistry , catalase , xanthine , lipopolysaccharide , nitric oxide synthase , superoxide , nitrite , biochemistry , intracellular , skeletal muscle , antioxidant , ascorbic acid , microbiology and biotechnology , enzyme , biology , endocrinology , nitrate , food science , organic chemistry
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.