Synthetic peroxisome proliferator-activated receptor gamma agonists rosiglitazone and troglitazone suppress transcription by promoter 3 of the human thromboxane A2 receptor gene in human erythroleukemia cells

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dc.contributor.author Coyle, Adrian T.
dc.contributor.author Kinsella, B. Therese
dc.date.accessioned 2011-09-02T14:35:05Z
dc.date.available 2011-09-02T14:35:05Z
dc.date.copyright 2006 Elsevier Inc. en
dc.date.issued 2006-04-28
dc.identifier.citation Biochemical Pharmacology en
dc.identifier.issn 0006-2952
dc.identifier.uri http://hdl.handle.net/10197/3149
dc.description.abstract The human thromboxane (TX)A2 receptor (TP) gene encodes two TP isoforms, TPalpha and TP beta that are regulated by distinct promoters designated promoter (Prm) 1 and Prm3, respectively. Previous studies established that 15d-delta 12,14-prostaglandin J2 (15d-PGJ2) selectively inhibits Prm3 activity and TP beta expression through a peroxisome proliferator-activated receptor (PPAR)gamma mechanism without affecting Prm1 activity or TPalpha expression in human megakaryocytic erythroleukemia (HEL) 92.1.7 cells. Herein, we investigated the effect of synthetic thiazolidinedione (TZD) PPARgamma ligands rosiglitazone and troglitazone on TP gene expression in HEL cells. Like 15d-PGJ2, both TZDs suppressed Prm3 activity, TPbeta mRNA expression and TP-mediated calcium mobilization without affecting Prm1 or TPalpha mRNA expression. However, unlike 15d-PGJ2, both TZDs mediated their PPARgamma-dependent effects through trans-repression of an activator protein-1 (AP-1) element, a site previously found to be critical for basal Prm3 activity. These data provide further evidence for the role of PPARgamma in regulating the human TP gene; they highlight further differences in TPalpha and TPbeta expression/regulation and point to essential differences between natural and synthetic PPARgamma agonists in mediating those effects. en
dc.description.sponsorship Health Research Board en
dc.format.extent 2364875 bytes
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.requires Biomolecular and Biomedical Science Research Collection en
dc.relation.requires Conway Institute Research Collection en
dc.rights This is the author’s version of a work that was accepted for publication in Biochemical Pharmacology. 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 Biochemical Pharmacology Volume 71, Issue 9, 28 April 2006, Pages 1308-1323 DOI 10.1016/j.bbalip.2006.07.012. en
dc.subject Thromboxane receptor en
dc.subject Promoter en
dc.subject Peroxisome proliferator-activated receptor (delta) en
dc.subject Thiazolidinedione en
dc.subject 15-deoxy -(grdelta)12,14-prostaglandin J2 en
dc.subject.lcsh Thromboxanes en
dc.subject.lcsh Promoters (Genetics) en
dc.subject.lcsh Cell receptors en
dc.subject.lcsh Thiazoles en
dc.subject.mesh Receptors, Thromboxane en
dc.subject.mesh Promoter Regions, Genetic en
dc.subject.mesh Peroxisome Proliferator-Activated Receptors en
dc.subject.mesh Thiazolidinediones en
dc.subject.mesh Prostaglandin D2--analogs & derivatives en
dc.title Synthetic peroxisome proliferator-activated receptor gamma agonists rosiglitazone and troglitazone suppress transcription by promoter 3 of the human thromboxane A2 receptor gene in human erythroleukemia cells en
dc.title.alternative Effect of thiazolidinedione derivatives on thromboxane A2 receptor gene expression en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.internal.webversions Publisher's version en
dc.internal.webversions http://dx.doi.org/10.1016/j.bcp.2006.01.011 en
dc.status Peer reviewed en
dc.identifier.volume 71 en
dc.identifier.issue 9 en
dc.identifier.startpage 1308 en
dc.identifier.endpage 1323 en
dc.identifier.doi 10.1016/j.bcp.2006.01.011 |
dc.neeo.contributor Coyle|Adrian T.|aut| en
dc.neeo.contributor Kinsella|B. Therese|aut| en
dc.description.othersponsorship Wellcome Trust en
dc.description.admin ot, ke, -SB01/09/2011 en


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