Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-2-11
pubmed:abstractText
The underlying redox-sensitive mechanisms that regulate hepatocyte expression of inducible nitric-oxide synthase (iNOS) and its antioxidant functions are largely unknown. We have demonstrated previously that oxidative stress induced by benzenetriol-mediated superoxide production increases interleukin-1beta-induced iNOS protein synthesis, steady state iNOS mRNA expression, NO production, iNOS gene transcription, and trans-activation of the iNOS promoter in primary cultures of rat hepatocytes. In this study, we extend these studies by establishing the sequence specificity and binding of nuclear protein to the previously described 15-base cis-regulatory element of the rat hepatocyte iNOS promoter, isolating and identifying the cis-regulatory element transcription factor as hepatocyte nuclear factor-4alpha (HNF-4alpha), and confirming the functional role of HNF-4alpha in mediating redox-sensitive iNOS promoter trans-activation. In addition, we demonstrate that binding of HNF-4alpha to the transcriptional coactivator, PC4, in the presence of oxidative stress and interleukin-1beta stimulation is essential for increased iNOS promoter activity in this setting. Our results indicate that HNF-4alpha is the transcription factor that mediates redox regulation of hepatocyte iNOS gene transcription.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 4, http://linkedlifedata.com/resource/pubmed/chemical/IFRD2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II, http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5054-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11741883-Animals, pubmed-meshheading:11741883-Binding Sites, pubmed-meshheading:11741883-Blotting, Western, pubmed-meshheading:11741883-Cells, Cultured, pubmed-meshheading:11741883-DNA-Binding Proteins, pubmed-meshheading:11741883-Gene Expression Regulation, Enzymologic, pubmed-meshheading:11741883-Hepatocyte Nuclear Factor 4, pubmed-meshheading:11741883-Hepatocytes, pubmed-meshheading:11741883-Immediate-Early Proteins, pubmed-meshheading:11741883-Male, pubmed-meshheading:11741883-Membrane Proteins, pubmed-meshheading:11741883-Mutagenesis, Site-Directed, pubmed-meshheading:11741883-Nitric Oxide, pubmed-meshheading:11741883-Nitric Oxide Synthase, pubmed-meshheading:11741883-Nitric Oxide Synthase Type II, pubmed-meshheading:11741883-Oxidation-Reduction, pubmed-meshheading:11741883-Oxidative Stress, pubmed-meshheading:11741883-Phosphoproteins, pubmed-meshheading:11741883-Precipitin Tests, pubmed-meshheading:11741883-Promoter Regions, Genetic, pubmed-meshheading:11741883-Protein Binding, pubmed-meshheading:11741883-Rats, pubmed-meshheading:11741883-Rats, Inbred Lew, pubmed-meshheading:11741883-Repressor Proteins, pubmed-meshheading:11741883-Trans-Activators, pubmed-meshheading:11741883-Transcription, Genetic, pubmed-meshheading:11741883-Transcription Factors, pubmed-meshheading:11741883-Transcriptional Activation, pubmed-meshheading:11741883-Transfection, pubmed-meshheading:11741883-Ultraviolet Rays
pubmed:year
2002
pubmed:articleTitle
Hepatocyte nuclear factor-4alpha mediates redox sensitivity of inducible nitric-oxide synthase gene transcription.
pubmed:affiliation
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't