Coyle, Adrian T.Adrian T.CoyleKinsella, B. ThereseB. ThereseKinsella2011-09-022011-09-022006 Elsev2006-04-28Biochemical Pharmacology0006-2952http://hdl.handle.net/10197/3149The 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.2364875 bytesapplication/pdfenThis 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.Thromboxane receptorPromoterPeroxisome proliferator-activated receptor (delta)Thiazolidinedione15-deoxy -(grdelta)12,14-prostaglandin J2ThromboxanesPromoters (Genetics)Cell receptorsThiazolesReceptors, ThromboxanePromoter Regions, GeneticPeroxisome Proliferator-Activated ReceptorsThiazolidinedionesProstaglandin D2--analogs & derivativesJournal Article7191308132310.1016/j.bcp.2006.01.011 |https://creativecommons.org/licenses/by-nc-sa/1.0/