Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors |
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Authors: | Gobeil Fernand Vazquez-Tello Alejandro Marrache Anne Marilise Bhattacharya Mosumi Checchin Daniella Bkaily Ghassan Lachapelle Pierre Ribeiro-Da-Silva Alfredo Chemtob Sylvain |
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Affiliation: | Department of Pharmacology, Université de Sherbrooke, 3001, 12th North Avenue, Fleurimont, Sherbrooke, QC J1H 5N4, Canada. fernand.gobeil@usherbrooke.ca |
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Abstract: | Prostaglandins are ubiquitous lipid mediators that play pivotal roles in cardiovascular homeostasis, reproduction, and inflammation, as well as in many important cellular processes including gene expression and cell proliferation. The mechanism of action of these lipid messengers is thought to be primarily dependent on their interaction with specific cell surface receptors that belong to the heptahelical transmembrane spanning G protein-coupled receptor superfamily. Accumulating evidence suggests that these receptors may co-localize at the cell nucleus where they can modulate gene expression through a series of biochemical events. In this context, we have recently demonstrated that prostaglandin E2-EP3 receptors display an atypical nuclear compartmentalization in cerebral microvascular endothelial cells. Stimulation of these nuclear EP3 receptors leads to an increase of eNOS RNA in a cell-free isolated nuclear system. This review will emphasize these findings and describe how nuclear prostaglandin receptors, notably EP3 receptors, may affect gene expression, specifically of eNOS, by identifying putative transducing elements located within this organelle. The potential sources of lipid ligand activators for these intracellular sites will also be addressed. The expressional control of G-protein-coupled receptors located at the perinuclear envelope constitutes a novel and distinctive mode of gene regulation. |
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