Linked Life Data

15365250

Source:http://linkedlifedata.com/resource/pubmed/id/15365250

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-14
pubmed:abstractText
The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both normal physiological functions and the pathogenesis of disease. This study was undertaken to determine the molecular mechanism by which nitric oxide (NO) exerts negative feedback regulation on iNOS gene expression. Isolated rat hepatocytes stimulated with cytokines exhibited a marked increase in NO production as well as iNOS mRNA and protein levels, which were significantly reduced by pretreatment of the NO donors S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and V-PYRRO/NO. This effect of SNAP was inhibited when NO was scavenged using red blood cells. Pretreatment with oxidized SNAP, 8-Br-cGMP, NO2-, or NO3- did not suppress the cytokine-induced NO production. Moreover, LPS/ IFN-gamma-stimulated RAW264.7 cells, which produce endogenous NO, expressed lower levels of iNOS, IL-1beta, IL-6 and TNF-alpha mRNAs, without changes in their mRNA half-lives, than those in the presence of the iNOS inhibitor NG-monomethyl-L-arginine. The iNOS gene transcription rate exhibited an 18-fold increase after cytokine stimulation, which was significantly inhibited by SNAP pretreatment. SNAP also blocked cytokine- induced increase in NF-kappaB activation, iNOS promoter activity, nuclear translocation of cytosolic NF-kappaB p65 subunit, and IkappaBalpha degradation, which correlated with its inhibitory effect on phosphorylation and ubiquitination of IkappaB. These data indicate that NO down-regulates iNOS gene expression and NO production by inhibiting the post-translational processes of IkappaBalpha thereby preventing NF-kappaB activation. These results identify a novel negative feedback mechanism whereby NO down-regulates iNOS gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1226-3613
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-24
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15365250-Animals, pubmed-meshheading:15365250-Cell Line, pubmed-meshheading:15365250-Cell Nucleus, pubmed-meshheading:15365250-Cyclic GMP, pubmed-meshheading:15365250-Cytokines, pubmed-meshheading:15365250-Down-Regulation, pubmed-meshheading:15365250-Hepatocytes, pubmed-meshheading:15365250-I-kappa B Proteins, pubmed-meshheading:15365250-Lipopolysaccharides, pubmed-meshheading:15365250-Nitric Oxide, pubmed-meshheading:15365250-Nitric Oxide Synthase, pubmed-meshheading:15365250-Nitric Oxide Synthase Type II, pubmed-meshheading:15365250-Penicillamine, pubmed-meshheading:15365250-Phosphorylation, pubmed-meshheading:15365250-Promoter Regions, Genetic, pubmed-meshheading:15365250-Protein Processing, Post-Translational, pubmed-meshheading:15365250-Protein Transport, pubmed-meshheading:15365250-Rats
pubmed:year
2004
pubmed:articleTitle
Nitric oxide suppresses inducible nitric oxide synthase expression by inhibiting post-translational modification of IkappaB.
pubmed:affiliation
Department of Molecular and Cellular Biochemistry, School of Medicine Kangwon National University, Chuncheon, Gangwon-do, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't