| Peroxide-inducible Ets-1 mediates platelet-derived growth factor receptor-alpha gene transcription in vascular smooth muscle cells. | |
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MedLine Citation:
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PMID: 16192649 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of vascular occlusive disorders such as atherosclerosis and restenosis in part due to its regulation of smooth muscle cell phenotype. The molecular mechanisms regulating the expression of PDGF-Ralpha, which binds all known dimeric forms of PDGF except PDGF-DD, are poorly understood. Here we demonstrate that the winged helix-turn-helix proto-oncogene Ets-1 controls PDGF-Ralpha transcription and mRNA expression in smooth muscle cells. Mutational analysis, electrophoretic mobility shift assay, and chromatin immunoprecipitation revealed the existence of a reverse Ets binding motif (-45TTCC-42) in the proximal region of the PDGF-Ralpha promoter, which bound both recombinant and endogenous Ets-1. Ets-1-inducible PDGF-Ralpha expression depended on the integrity of both the -45TTCC-42 motif and the -61G10(-52) element, which resides upstream of -45TTCC-42 and mediates Sp1 induction. Hydrogen peroxide (H2O2) at nanomolar concentrations stimulated levels of Ets-1 and increased PDGF-Ralpha transcription and mRNA expression without affecting Sp1 expression. H2O2 activation of the PDGF-Ralpha promoter was abolished by disrupting -45TTCC-42 or -61G10(-52). These studies identify a functional Ets motif in the PDGF-Ralpha promoter that plays a pivotal role in agonist-inducible PDGF-Ralpha transcription. |
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Authors:
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Michelle R Bonello; Yuri V Bobryshev; Levon M Khachigian |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of pathology Volume: 167 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-29 Completed Date: 2005-11-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1149-59 Citation Subset: AIM; IM |
Affiliation:
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Centre for Vascular Research, Department of Pathology, The University of New South Wales, Sydney, NSW 2052, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta / cytology Arteriosclerosis / metabolism, pathology Blotting, Western Carotid Arteries / pathology Cell Proliferation Cells, Cultured Chromatin Immunoprecipitation Dose-Response Relationship, Drug Electrophoretic Mobility Shift Assay Genes, Reporter Humans Hydrogen Peroxide / pharmacology* Luciferases / metabolism Muscle, Smooth, Vascular / metabolism* Mutation Oligonucleotides, Antisense / pharmacology Oxidants / pharmacology* Promoter Regions, Genetic Proto-Oncogene Protein c-ets-1 / genetics, metabolism* RNA, Messenger / metabolism Rats Rats, Inbred WKY Receptors, Platelet-Derived Growth Factor / genetics* Sp1 Transcription Factor / metabolism Transcription, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/ETS1 protein, human; 0/Oligonucleotides, Antisense; 0/Oxidants; 0/Proto-Oncogene Protein c-ets-1; 0/RNA, Messenger; 0/Sp1 Transcription Factor; 7722-84-1/Hydrogen Peroxide; EC 1.13.12.-/Luciferases; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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