Document Detail


Nitric oxide synthase isoform expression in acute versus chronic anti-Thy 1 nephritis.
MedLine Citation:
PMID:  11849433     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Two inbred Lewis rat substrains (LEW/Moe, LEW/Maa) were identified responding differently to induction of anti-Thy 1 glomerulonephritis (aThy 1-GN). LEW/Moe rats show an acute mesangioproliferative glomerulonephritis with rapid healing of glomerular lesions within four weeks, while LEW/Maa rats develop severe glomerular injury followed by chronic glomerular sclerosis and persistent albuminuria. We investigated whether the glomerular expression pattern of nitric oxide synthase (NOS) isoforms could explain these substrain-related differences. METHODS: Rats (N = 5 to 7 per group) were investigated in a time course experiment. Severity of aThy 1-GN was determined by albuminuria measurements, glomerular matrix score and microaneurysm formation. Glomerular gene expression of NOS isoforms was determined by semiquantitative RT-PCR. Inducible NOS (iNOS) activity was determined in cultured glomeruli and peritoneal macrophages. Neuronal NOS (nNOS) protein expression was detected by Western blotting and enzyme histochemistry. Plasma renin activity (PRA) was measured by RIA. RESULTS: Induction of iNOS expression and activity was found significantly increased and sustained in LEW/Maa vs. LEW/Moe rats associated with an increased number of infiltrating macrophages and with an increased capacity of iNOS-expression and iNOS-activation by isolated macrophages in LEW/Maa rats. Glomerular nNOS mRNA and nNOS protein expression were constitutively increased in LEW/Maa rats. Renal nNOS localization was restricted to the macula densa region in both substrains and associated with increased PRA in LEW/Maa rats. No difference in glomerular endothelial NOS-mRNA expression between the substrains was observed. CONCLUSIONS: Increased glomerular iNOS and nNOS expression were associated with chronic anti-Thy 1 glomerulonephritis in LEW/Maa rats and may contribute to glomerular damage by separate mechanisms.
Authors:
Markus Ketteler; Ralf Westenfeld; Alexander Gawlik; Sebastian Bachmann; Alexander Frey; Gilbert Schönfelder; Martin Paul; Armin Distler; Emile de Heer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international     Volume:  61     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-02-18     Completed Date:  2002-05-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  826-33     Citation Subset:  IM    
Affiliation:
Department of Medicine II, University Hospital Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany. mketteler@ukaachen.de
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Chronic Disease
Isoantibodies / immunology*
Nephritis / enzymology*,  immunology*
Nitric Oxide Synthase / genetics,  metabolism*
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
RNA, Messenger / metabolism
Rats
Rats, Inbred Lew
Chemical
Reg. No./Substance:
0/Isoantibodies; 0/RNA, Messenger; 0/anti-Thy antibody; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos1 protein, rat; EC 1.14.13.39/Nos2 protein, rat

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