Potentiation of nitric oxide synthase expression by superoxide in interleukin 1β-stimulated rat mesangial cells

被引：42

作者：

Beck, KF ^{[1
]}

Eberhardt, W ^{[1
]}

Walpen, S ^{[1
]}

Apel, M ^{[1
]}

Pfeilschifter, J ^{[1
]}

机构：

[1] Univ Frankfurt Klinikum, Zentrum Pharmakol, D-60590 Frankfurt, Germany

来源：

FEBS LETTERS | 1998年 / 435卷 / 01期

关键词：

inducible nitric oxide synthase regulation; superoxide; nitric oxide; mesangial cell; rat;

D O I：

10.1016/S0014-5793(98)01035-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Exposure of mesangial cells to superoxide, generated by the hypoxanthine/xanthine oxidase system or by the redox cycler 2,3-dimethoxy-1,4-naphthoquinone caused a concentration-dependent amplification of interleukin (IL)-1 beta-stimulated nitrite production. The effect of superoxide was accompanied by an increase in inducible nitric oxide synthase (iNOS) protein and iNOS mRNA levels, Incubation of mesangial cells with superoxide alone did not induce iNOS expression. To elucidate whether the increase of iNOS expression is due to transcriptional upregulation we fused a 4.5-kb genomic iNOS fragment that contains the transcriptional start site of the rat iNOS gene to a luciferase reporter gene. In transient transfection studies, superoxide caused a 10-fold augmentation of iNOS promoter activity in IL-1 beta-challenged mesangial cells. Our data identify superoxide as a co-stimulatory factor amplifying cytokine-induced iNOS gene expression and subsequent nitric oxide (NO) synthesis. (C) 1998 Federation of European Biochemical Societies.

引用

页码：35 / 38

页数：4

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