Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1998-10-1
pubmed:abstractText
Reactive oxygen species generated by treatment of smooth muscle cells (SMCs) with either phorbol 12-myristate 13-acetate or with the combination of H2O2 and vanadate strongly induce expression of the class A scavenger receptor (SR-A) gene. In the current studies, cis-acting elements in the proximal 245 bp of the SR-A promoter were shown to direct luciferase reporter expression in response to oxidative stress in both SMCs and macrophages. A composite activating protein-1 (AP-1)/ets binding element located between -67 and -50 bp relative to the transcriptional start site is critical for macrophage SR-A activity. Mutation of either the AP-1 or the ets component of this site also prevented promoter activity in SMCs. Mutation of a second site located between -44 and -21 bp, which we have identified as a CCAAT/enhancer binding protein (C/EBP) element, reduced the inducible activity of the promoter in SMCs by 50%, suggesting that combinatorial interactions between these sites are necessary for optimal gene induction. Interactions between SMC nuclear extracts and the SR-A promoter were analyzed by electrophoretic mobility shift assay. c-Jun/AP-1 binding activity, specific for the -67- to -50-bp site, was induced in SMCs by the same conditions that increased SR-A expression. Moreover, phorbol 12-myristate 13-acetate, H2O2, or the combination of H2O2 and sodium orthovanadate (vanadate) activated c-Jun-activating kinase. The binding activity within SMC extracts specific for the C/EBP site was shown to be C/EBPbeta in SMCs. Taken together, these findings demonstrate that reactive oxygen species regulate the interactions between c-Jun/AP-1 and C/EBPbeta in the SR-A promoter. Furthermore, induction of oxidative stress in THP-1 cells, with a combination of 10 micromol/L vanadate and 100 micromol/L H2O2, induced macrophage differentiation, adhesion, and SR activity. These data suggest that vascular oxidative stress may contribute to the induction of SR-A expression and thereby promote the uptake of oxidatively modified low density lipoprotein by both macrophage and SMCs to produce foam cells in atherosclerotic lesions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase..., http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lipoprotein, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Scavenger, http://linkedlifedata.com/resource/pubmed/chemical/Scarb1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Scavenger Receptors, Class A, http://linkedlifedata.com/resource/pubmed/chemical/Scavenger Receptors, Class B, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1079-5642
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1440-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9743233-Animals, pubmed-meshheading:9743233-Binding Sites, pubmed-meshheading:9743233-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:9743233-Cell Line, pubmed-meshheading:9743233-DNA, pubmed-meshheading:9743233-DNA-Binding Proteins, pubmed-meshheading:9743233-Gene Expression, pubmed-meshheading:9743233-Humans, pubmed-meshheading:9743233-Hydrogen Peroxide, pubmed-meshheading:9743233-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:9743233-MAP Kinase Kinase 4, pubmed-meshheading:9743233-Macrophages, pubmed-meshheading:9743233-Membrane Proteins, pubmed-meshheading:9743233-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:9743233-Muscle, Smooth, pubmed-meshheading:9743233-Mutation, pubmed-meshheading:9743233-Nuclear Proteins, pubmed-meshheading:9743233-Oxidative Stress, pubmed-meshheading:9743233-Promoter Regions, Genetic, pubmed-meshheading:9743233-Protein Kinases, pubmed-meshheading:9743233-Proto-Oncogene Proteins c-jun, pubmed-meshheading:9743233-Rabbits, pubmed-meshheading:9743233-Receptors, Immunologic, pubmed-meshheading:9743233-Receptors, Lipoprotein, pubmed-meshheading:9743233-Receptors, Scavenger, pubmed-meshheading:9743233-Scavenger Receptors, Class A, pubmed-meshheading:9743233-Scavenger Receptors, Class B, pubmed-meshheading:9743233-Tetradecanoylphorbol Acetate, pubmed-meshheading:9743233-Transcription, Genetic, pubmed-meshheading:9743233-Transcription Factor AP-1
pubmed:year
1998
pubmed:articleTitle
Transcriptional activation of scavenger receptor expression in human smooth muscle cells requires AP-1/c-Jun and C/EBPbeta: both AP-1 binding and JNK activation are induced by phorbol esters and oxidative stress.
pubmed:affiliation
Gladstone Institute of Cardiovascular Disease, and Department of Pediatrics, University of California, San Francisco 94141-9100, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.