Estrogen increases expression of the human prostacyclin receptor within the vasculature through an ERα-dependent mechanism

DC FieldValueLanguage
dc.contributor.authorTurner, Elizebeth C.-
dc.contributor.authorKinsella, B. Therese-
dc.date.accessioned2011-09-21T15:26:35Z-
dc.date.available2011-09-21T15:26:35Z-
dc.date.copyright2010 Elsevier Ltden
dc.date.issued2010-02-26-
dc.identifier.citationJournal of Molecular Biologyen
dc.identifier.issn0022-2836-
dc.identifier.urihttp://hdl.handle.net/10197/3162-
dc.description.abstractProstacyclin and the prostacyclin receptor (IP) are implicated in mediating many of the atheroprotective effects of estrogen in both humans and in animal models but through unknown mechanisms. Hence, herein the influence of estrogen on IP gene expression in endothelial EA.hy926, human erythroleukemia 92.1.7 and primary human (h) aortic smooth muscle (1o hAoSM) cells was investigated. Estrogen increased hIP mRNA levels, promoter (PrmIP)-directed reporter gene expression and cicaprost-dependent cAMP generation in all cell types, effects that were abrogated by actinomycinD and the general estrogen receptor (ER)-α/ERβ antagonist ICI 182,780. Furthermore, the ERα-selective agonist 4,4’,4”-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), but not the ERβ-agonist 2,3-bis(4-Hydroxyphenly)-propionitrile, significantly increased hIP mRNA and PrmIP-directed gene expression. Deletional and mutational analysis of PrmIP uncovered an evolutionary conserved estrogen-response element (ERE) while electrophoretic mobility shift, antibody-supershift and chromatin immunoprecipitations assays confirmed the direct binding of ERα, but not ERβ, to PrmIP both in vitro and in vivo. Moreover, immunofluorescence microscopy corroborated that estrogen and PPT increased hIP expression in 1o hAoSMCs. In conclusion, the hIP gene is directly regulated by estrogen that largely occurs through an ERα-dependent transcriptional mechanism and thereby provides critical insights into the role of prostacyclin/hIP in mediating the atheroprotective effects of estrogen within the human vasculature.en
dc.description.sponsorshipScience Foundation Irelanden
dc.description.sponsorshipHealth Research Boarden
dc.format.extent765132 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherElsevieren
dc.relation.requiresBiomolecular and Biomedical Science Research Collectionen
dc.relation.requiresConway Institute Research Collectionen
dc.rightsThis is the author’s version of a work that was accepted for publication in Journal of Molecular Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Molecular Biology, 396 (3): 473-486 DOI 10.1016/j.jmb.2010.01.010.en
dc.subjectProstacyclin receptoren
dc.subjectEstrogenen
dc.subjectGene expressionen
dc.subjectTranscriptionen
dc.subjectEstrogen-response element (ERE)en
dc.subjectPromoteren
dc.subject.lcshProstacyclin--Receptorsen
dc.subject.lcshGene expressionen
dc.subject.lcshTranscription factorsen
dc.subject.lcshEstrogenen
dc.subject.lcshPromoters (Genetics)en
dc.subject.meshReceptors, Epoprostenolen
dc.subject.meshGene Expressionen
dc.subject.meshTranscription Factorsen
dc.subject.meshResponse Elementsen
dc.subject.meshPromoter Regions, Geneticen
dc.titleEstrogen increases expression of the human prostacyclin receptor within the vasculature through an ERα-dependent mechanismen
dc.title.alternativeProstacyclin receptor gene regulation by estrogenen
dc.typeJournal Articleen
dc.internal.availabilityFull text availableen
dc.internal.webversionshttp://dx.doi.org/10.1016/j.jmb.2010.01.010-
dc.statusPeer revieweden
dc.identifier.volume396en
dc.identifier.issue3en
dc.identifier.startpage473en
dc.identifier.endpage486en
dc.identifier.doi10.1016/j.jmb.2010.01.010-
dc.neeo.contributorTurner|Elizebeth C.|aut|-
dc.neeo.contributorKinsella|B. Therese|aut|-
dc.description.adminot,ke, -SB01/09/2011en
item.grantfulltextopen-
item.fulltextWith Fulltext-
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Biomolecular and Biomedical Science Research Collection
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