HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 40, 38875-38883, October 3, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/40/38875    most recent M212481200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gobeil, F. Articles by Chemtob, S. Search for Related Content PubMed PubMed Citation Articles by Gobeil, F., Jr. Articles by Chemtob, S. Social Bookmarking                      What's this?

Modulation of Pro-inflammatory Gene Expression by Nuclear Lysophosphatidic Acid Receptor Type-1^*

Fernand Gobeil, Jr.  , Sylvie G. Bernier , Alejandro Vazquez-Tello , Sonia Brault  ¶, Martin H. Beauchamp , Christiane Quiniou , Anne Marilise Marrache  ¶, Daniella Checchin  ¶, Florian Sennlaub , Xin Hou , Mony Nader ||, Ghassan Bkaily ||, Alfredo Ribeiro-da-Silva ¶, Edward J. Goetzl ** and Sylvain Chemtob  ¶ 

From the Departments of Pediatrics, Ophthalmology and Pharmacology, Research Center of Hôpital Sainte-Justine, Montréal, Québec H3T 1C5, Canada, the ^||Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada, the ^¶Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec H3G 1Y6, Canada, and the ^**Department of Medicine and Microbiology-Immunology, University of California, San Francisco, California 94143-0711

Lysophosphatidic acid (LPA) is a bioactive molecule involved in inflammation, immunity, wound healing, and neoplasia. Its pleiotropic actions arise presumably by interaction with their cell surface G protein-coupled receptors. Herein, the presence of the specific nuclear lysophosphatidic acid receptor-1 (LPA₁R) was revealed in unstimulated porcine cerebral microvascular endothelial cells (pCMVECs), LPA₁R stably transfected HTC4 rat hepatoma cells, and rat liver tissue using complementary approaches, including radioligand binding experiments, electron- and cryomicroscopy, cell fractionation, and immunoblotting with three distinct antibodies. Coimmunoprecipitation studies in enriched plasmalemmal fractions of unstimulated pCMVEC showed that LPA₁Rs are dually sequestrated in caveolin-1 and clathrin subcompartments, whereas in nuclear fractions LPA₁R appeared primarily in caveolae. Immunofluorescent assays using a cell-free isolated nuclear system confirmed LPA₁R and caveolin-1 co-localization. In pCMVEC, LPA-stimulated increases in cyclooxygenase-2 and inducible nitric-oxide synthase RNA and protein expression were insensitive to caveolea-disrupting agents but sensitive to LPA-generating phospholipase A₂ enzyme and tyrosine kinase inhibitors. Moreover, LPA-induced increases in Ca²⁺ transients and/or iNOS expression in highly purified rat liver nuclei were prevented by pertussis toxin, phosphoinositide 3-kinase/Akt inhibitor wortmannin and Ca²⁺ chelator and channel blockers EGTA and SK&F96365, respectively. This study describes for the first time the nucleus as a potential organelle for LPA intracrine signaling in the regulation of pro-inflammatory gene expression.

Received for publication, December 9, 2002 , and in revised form, June 18, 2003.

^* This work was supported in part by grants from the Canadian Institute of Health Research (CIHR), the Heart and Stroke Foundation of Québec, and the March of Dimes and by the National Institutes of Health Grant HL-31809. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

A recipient of a Canada Research Chair.

A recipient of a fellowship award from the CIHR and is currently on professorship staff at the University of Sherbrooke. To whom correspondence should be addressed: Dept. of Pharmacology, Université de Sherbrooke, 3001, 12th North Ave., Fleurimont, Québec J1H 5N4, Canada. Tel.: 819-564-5341; Fax: 819-564-5400; E-mail: Fernand.Gobeil{at}USherbrooke.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. U. Schraufstatter, R. G. DiScipio, M. Zhao, and S. K. Khaldoyanidi C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation J. Immunol., March 15, 2009; 182(6): 3827 - 3836. [Abstract] [Full Text] [PDF]

				E. Liszewska, P. Reinaud, E. Billon-Denis, O. Dubois, P. Robin, and G. Charpigny Lysophosphatidic Acid Signaling during Embryo Development in Sheep: Involvement in Prostaglandin Synthesis Endocrinology, January 1, 2009; 150(1): 422 - 434. [Abstract] [Full Text] [PDF]

				H. P. Kim and A. M. K. Choi Caveolin-1 stops profibrogenic signaling? Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L841 - L842. [Full Text] [PDF]

				E. J. Goetzl Diverse pathways for nuclear signaling by G protein-coupled receptors and their ligands FASEB J, March 1, 2007; 21(3): 638 - 642. [Abstract] [Full Text] [PDF]

				S. Brault, F. Gobeil Jr., A. Fortier, J.-C. Honore, J.-S. Joyal, P. S. Sapieha, A. Kooli, E. Martin, P. Hardy, A. Ribeiro-da-Silva, et al. Lysophosphatidic acid induces endothelial cell death by modulating the redox environment Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1174 - R1183. [Abstract] [Full Text] [PDF]

				J.-J. Liao, M.-C. Huang, M. Graler, Y. Huang, H. Qiu, and E. J. Goetzl Distinctive T Cell-suppressive Signals from Nuclearized Type 1 Sphingosine 1-Phosphate G Protein-coupled Receptors J. Biol. Chem., January 19, 2007; 282(3): 1964 - 1972. [Abstract] [Full Text] [PDF]

				C. Pilquil, J. Dewald, A. Cherney, I. Gorshkova, G. Tigyi, D. English, V. Natarajan, and D. N. Brindley Lipid Phosphate Phosphatase-1 Regulates Lysophosphatidate-induced Fibroblast Migration by Controlling Phospholipase D2-dependent Phosphatidate Generation J. Biol. Chem., December 15, 2006; 281(50): 38418 - 38429. [Abstract] [Full Text] [PDF]

				C. Han, A. J. Demetris, D. B. Stolz, L. Xu, K. Lim, and T. Wu Modulation of Stat3 Activation by the Cytosolic Phospholipase A2{alpha} and Cyclooxygenase-2-controlled Prostaglandin E2 Signaling Pathway J. Biol. Chem., August 25, 2006; 281(34): 24831 - 24846. [Abstract] [Full Text] [PDF]

				B. Boivin, C. Lavoie, G. Vaniotis, A. Baragli, L.-R. Villeneuve, N. Ethier, P. Trieu, B. G. Allen, and T. E. Hebert Functional {beta}-adrenergic receptor signalling on nuclear membranes in adult rat and mouse ventricular cardiomyocytes Cardiovasc Res, July 1, 2006; 71(1): 69 - 78. [Abstract] [Full Text] [PDF]

				F. Gobeil Jr., T. Zhu, S. Brault, A. Geha, A. Vazquez-Tello, A. Fortier, D. Barbaz, D. Checchin, X. Hou, M. Nader, et al. Nitric Oxide Signaling via Nuclearized Endothelial Nitric-oxide Synthase Modulates Expression of the Immediate Early Genes iNOS and mPGES-1 J. Biol. Chem., June 9, 2006; 281(23): 16058 - 16067. [Abstract] [Full Text] [PDF]

				M. Enari, K. Ohmori, I. Kitabayashi, and Y. Taya Requirement of clathrin heavy chain for p53-mediated transcription Genes & Dev., May 1, 2006; 20(9): 1087 - 1099. [Abstract] [Full Text] [PDF]

				K. E. Morris, L. M. Schang, and D. N. Brindley Lipid Phosphate Phosphatase-2 Activity Regulates S-phase Entry of the Cell Cycle in Rat2 Fibroblasts J. Biol. Chem., April 7, 2006; 281(14): 9297 - 9306. [Abstract] [Full Text] [PDF]

				C. Quiniou, F. Sennlaub, M. H. Beauchamp, D. Checchin, I. Lahaie, S. Brault, F. Gobeil Jr., M. Sirinyan, A. Kooli, P. Hardy, et al. Dominant Role for Calpain in Thromboxane-Induced Neuromicrovascular Endothelial Cytotoxicity J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 618 - 627. [Abstract] [Full Text] [PDF]

				M. Rahaman, R. W. Costello, K. E. Belmonte, S. S. Gendy, and M.-T. Walsh Neutrophil Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors in Pneumonia Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 233 - 241. [Abstract] [Full Text] [PDF]

				J. Rubenfeld, J. Guo, N. Sookrung, R. Chen, W. Chaicumpa, V. Casolaro, Y. Zhao, V. Natarajan, and S. Georas Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L66 - L74. [Abstract] [Full Text] [PDF]

				I. Harfi, F. Corazza, S. D'Hondt, and E. Sariban Differential Calcium Regulation of Proinflammatory Activities in Human Neutrophils Exposed to the Neuropeptide Pituitary Adenylate Cyclase-Activating Protein J. Immunol., September 15, 2005; 175(6): 4091 - 4102. [Abstract] [Full Text] [PDF]

				I. Ben-Shlomo and A. J. W. Hsueh Three's Company: Two or More Unrelated Receptors Pair with the Same Ligand Mol. Endocrinol., May 1, 2005; 19(5): 1097 - 1109. [Abstract] [Full Text] [PDF]