Interactions between inducible nitric oxide synthase and heme oxygenase-1 in glomerulonephritis

被引:29
作者
Datta, PK [1 ]
Gross, EJ [1 ]
Lianos, EA [1 ]
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Div Nephrol, New Brunswick, NJ 08903 USA
关键词
iNOS; HO-1; nephritis; oxidative injury; inflammation;
D O I
10.1046/j.1523-1755.2002.00231.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. In anti-glomerular basement membrane (GBM) nephritis, inducible nitric oxide synthase (iNOS) and heme oxygenase (HO-1) are co-induced. Moreover, in glomerular mesangial cells iNOS-derived nitric oxide (NO) production stimulates HO-1 while HO-1 activation reduces iNOS expression/ activity. These observations prompted us to explore regulatory interactions between iNOS and HO-1 in anti-GBM nephritis. Methods. Rats with anti-GBM nephritis were pretreated with the iNOS inhibitor L-N-6-(1-iminoethyl) lysine (L-NIL) or with the HO-1 inducer hemin, Glomerular HO-1 levels were assessed by Western blot analysis. iNOS activity was assessed by calculating conversion Of L-arginine to L-Citrulline. Results. iNOS inhibition reduced glomerular HO-1 levels without altering the inflammatory response to anti-GBM antibody induced injury. Induction of HO-1 reduced glomerular iNOS activity. Conclusions. In anti-GBM nephritis iNOS up-regulates HO-1 presumably via high output NO production. Suprainduction of HO-1 attenuates iNOS activity. This negative feedback interaction points to HO-1 as a target for pharmacologic manipulation to reduce activity of prooxidant heme containing enzymes such as iNOS.
引用
收藏
页码:847 / 850
页数:4
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