Wu Feng, Tyml Karel, Wilson John X
Lawson Health Research Institute, University of Western Ontario, London, ON, Canada N6A 5C1.
FEBS Lett. 2002 Jun 5;520(1-3):122-6. doi: 10.1016/s0014-5793(02)02804-1.
Lipopolysaccharide endotoxin and interferon-gamma 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 NF kappa B. These results indicate that ascorbate inhibits iNOS expression in ECs by an antioxidant mechanism independent of both NF kappa B activation and the reported negative feedback effect of nitric oxide.
脂多糖内毒素和干扰素-γ可诱导大鼠骨骼肌微血管内皮细胞培养物（ECs）中诱导型一氧化氮合酶（iNOS）蛋白表达及亚硝酸盐/硝酸盐生成。用抗坏血酸预处理ECs会使细胞内积累大量抗坏血酸，从而降低细胞内氧化剂水平并减少iNOS的诱导。在黄嘌呤氧化酶/黄嘌呤加过氧化氢酶产生的外源性超氧化物存在的情况下，抗坏血酸的这些作用被消除，但当应用N-硝基-L-精氨酸甲酯抑制一氧化氮合成时，其作用未改变。抗坏血酸还减弱了转录因子IRF-1的激活，但不影响NF-κB的激活。这些结果表明，抗坏血酸通过一种独立于NF-κB激活和一氧化氮所报道的负反馈作用的抗氧化机制抑制ECs中iNOS的表达。
