Dual role of endogenous nitric oxide in tumor necrosis factor shock: induced NO tempers oxidative stress

被引:19
作者
Cauwels, A
Bultinck, J
Brouckaert, P
机构
[1] Univ Ghent, Dept Mol Biomed Res, Mol Pathophysiol & Expt Therapy Unit, B-9052 Ghent, Zwijnaarde, Belgium
[2] Flanders Interuniv Inst Biotechnol, B-9052 Ghent, Zwijnaarde, Belgium
关键词
mice; TNF shock; nitric oxide; oxidative stress;
D O I
10.1007/s00018-005-5142-z
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
Tumor necrosis factor (TNF) is involved in pathologies like septic shock, inflammatory bowel disease and rheumatoid arthritis. TNF and lipopolysaccharide can incite lethal shock, in which cardiovascular collapse is centrally orchestrated by the vasodilating free radical nitric oxide (NO). However, NO synthase (NOS) inhibition causes increased morbidity and/or mortality, suggesting a dual role for NO. To investigate the potential protective role of NO during TNF shock, we treated mice with TNF with or without NOS inhibition. Experiments in endothelial-NOS- and inducible NOS-deficient mice identified inducible NOS as the source of protective NO. Distinctive TNF-induced lipid peroxidation, especially in liver and kidney, was aggravated by NOS inhibition. In addition, various antioxidant treatments and a phospholipase A2 (PLA2) inhibitor prevented sensitization by NOS inhibition. Together, these in vivo results indicate that induced NO not only causes hemodynamic collapse, but is also essential for curbing TNF-induced oxidative stress, which appears to hinge on PLA2-dependent mechanisms.
引用
收藏
页码:1632 / 1640
页数:9
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