title: Nuclear prostaglandin signaling system: biogenesis and actions via heptahelical receptors.
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.
authors.affiliation: Department of Pharmacology, Université de Sherbrooke, 3001, 12th North Avenue, Fleurimont, Sherbrooke, QC J1H 5N4, Canada. fernand.gobeil@usherbrooke.ca
authors.forename: Fernand
authors.initials: F
authors.lastname: Gobeil
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Tello
authors.forename: Anne Marilise
authors.initials: AM
authors.lastname: Marrache
authors.forename: Mosumi
authors.initials: M
authors.lastname: Bhattacharya
authors.forename: Daniella
authors.initials: D
authors.lastname: Checchin
authors.forename: Ghassan
authors.initials: G
authors.lastname: Bkaily
authors.forename: Pierre
authors.initials: P
authors.lastname: Lachapelle
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-Da-Silva
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000818:Animals; D020555:GTP-Binding Protein Regulators / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D009685:Nuclear Envelope / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D011453:Prostaglandins / Q000235:genetics* / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
chemical_list: D020555:GTP-Binding Protein Regulators; D011453:Prostaglandins; D018078:Receptors, Prostaglandin E