Linked Life Data

9714306

Source:http://linkedlifedata.com/resource/pubmed/id/9714306

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-8-31
pubmed:databankReference
pubmed:abstractText
We have cloned five DNA fragments (-0.32, -0.48, -1.7, -3.2, and -5.1 kb) of the 5'-flanking region of the rat inducible nitric oxide synthase (iNOS) gene from rat genomic DNA. The functional importance of the 5'-flanking region was determined by transient expression of iNOS promoter-luciferase constructs in cultures of rat aortic smooth muscle cells. The -0.48 kb construct, containing one nuclear factor kappaB (NF-kappaB) binding site, expressed basal promoter activity but showed only a 1.5- and 1.7-fold increase in luciferase activity in response to lipopolysaccharide (LPS) or a cytokine mixture, respectively. However, the -3.2 kb construct (containing a second NF-kappaB binding site) showed full promoter activity with a 24-fold increase in response to LPS or cytokine mixture. The -5.1 kb construct showed no further increase in luciferase activity, suggesting that the 1.9 kb upstream of -3.2 kb may not be important in rat iNOS regulation. Rat iNOS promoter induction did not appear to be transcriptionally regulated by NO since NOS inhibitors did not affect induction. These data are in marked contrast to the mouse iNOS promoter in which a DNA sequence as short as a -85 bp, containing one NF-kappaB site, confers 10-fold inducibility by LPS. The present findings demonstrate that the rat iNOS gene is transcriptionally regulated by cytokines and LPS, but, unlike the mouse gene, the downstream NF-kappaB site does not appear to be a key region in responses to cytokines and LPS. These data suggest that the regulation of the rat gene may require the coexistence of at least two NF-kappaB sites or other elements upstream of -0.48 kb of the 5'-flanking region.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1873-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9714306-Animals, pubmed-meshheading:9714306-Aorta, pubmed-meshheading:9714306-Base Sequence, pubmed-meshheading:9714306-Cells, Cultured, pubmed-meshheading:9714306-Cloning, Molecular, pubmed-meshheading:9714306-Cytokines, pubmed-meshheading:9714306-DNA, pubmed-meshheading:9714306-Enzyme Induction, pubmed-meshheading:9714306-Enzyme Inhibitors, pubmed-meshheading:9714306-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9714306-Lipopolysaccharides, pubmed-meshheading:9714306-Molecular Sequence Data, pubmed-meshheading:9714306-Muscle, Smooth, Vascular, pubmed-meshheading:9714306-NF-kappa B, pubmed-meshheading:9714306-Nitric Oxide, pubmed-meshheading:9714306-Nitric Oxide Synthase, pubmed-meshheading:9714306-Nitric Oxide Synthase Type II, pubmed-meshheading:9714306-Promoter Regions, Genetic, pubmed-meshheading:9714306-Rats, pubmed-meshheading:9714306-Rats, Wistar
pubmed:year
1998
pubmed:articleTitle
Molecular cloning and analysis of the rat inducible nitric oxide synthase gene promoter in aortic smooth muscle cells.
pubmed:affiliation
Vascular Biology Center and Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2500, USA. hzhang@mail.mcg.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.