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

  • Western University

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

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.

Original languageEnglish
Article number26140
Pages (from-to)122-126
Number of pages5
JournalFEBS Letters
Volume520
Issue number1-3
DOIs
StatePublished - 2002

Keywords

  • Ascorbate
  • Endothelial cells
  • Inducible nitric oxide synthase
  • Oxidant
  • Sepsis

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