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IP receptor-dependent activation of PPAR gamma by stable prostacyclin analogues

Falcetti, E; Flavell, DM; Staels, B; Tinker, A; Haworth, SG; Clapp, LH; (2007) IP receptor-dependent activation of PPAR gamma by stable prostacyclin analogues. BIOCHEM BIOPH RES CO , 360 (4) 821 - 827. 10.1016/j.bbrc.2007.06.135. Gold open access

Abstract

Stable prostacyclin analogues can signal through cell surface IP receptors or by ligand binding to nuclear peroxisome proliferator-activated receptors. (PPARs). So far these agents have been reported to activate PPAR alpha and PPAR delta but not PPAR gamma. Given PPAR gamma agonists and prostacyclin analogues both inhibit cell proliferation, we postulated that the IP receptor might elicit PPAR gamma activation. Using a dual luciferase reporter gene assay in HEK-293 cells stably expressing the IP receptor or empty vector, we found that prostacyclin analogues only activated PPAR gamma in the presence of the IP receptor. Moreover, the novel IP receptor antagonist, RO1138452, but not inhibitors of the cyclic AMP pathway, prevented activation. Likewise, the anti-proliferative effects of treprostinil observed in IP receptor expressing cells, were partially inhibited by the PPAR gamma antagonist, GW9662. We conclude that PPAR gamma is activated through the IP receptor via a cyclic AMP-independent mechanism and contributes to the anti-growth effects of prostacyclin analogues. (c) 2007 Elsevier Inc. All rights reserved.

Type: Article
Title: IP receptor-dependent activation of PPAR gamma by stable prostacyclin analogues
Open access status: An open access publication
DOI: 10.1016/j.bbrc.2007.06.135
Publisher version: http://ukpmc.ac.uk/abstract/MED/17624303
Keywords: prostacyclin (IP) receptor, peroxisome proliferator-activated receptors, luciferase reporter gene assay, prostacyclin analogues, cell proliferation, NUCLEAR RECEPTORS, PEROXISOME, ALPHA, PHOSPHORYLATION, DELTA, ANTAGONISTS, EXPRESSION, CHANNELS, LIGANDS, INSULIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/175749
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