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

This Article Full Text Full Text (PDF) All Versions of this Article: M500095-JLR200v1 46/9/1833    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johnstone, E. D. Articles by Guilbert, L. J. Search for Related Content PubMed PubMed Citation Articles by Johnstone, E. D. Articles by Guilbert, L. J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 1833-1839, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Sphingosine-1-phosphate inhibition of placental trophoblast differentiation through a G_i-coupled receptor response

Edward D. Johnstone^*,, Gary Chan^*,**, Colin P. Sibley, Sandra T. Davidge^,**, Bonnie Lowen^* and Larry J. Guilbert^1,*,**

^* Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada
^** Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada
Academic Unit of Child Health, University of Manchester, Manchester, United Kingdom

Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.M500095-JLR200

¹ To whom correspondence should be addressed. e-mail: larry.guilbert{at}ualberta.ca

The failure of placental trophoblasts to differentiate properly is thought to play an important role in the cause of pregnancy disorders such as preeclampsia. We looked at the effects of the bioactive lipid sphingosine-1-phosphate (S1P) on the differentiation of primary human cytotrophoblasts (CTs) into syncytiotrophoblasts (STs) in culture. We found that S1P inhibited CT differentiation measured by human chorionic gonadotropin (hCG) secretion and the expression of placental alkaline phosphatase but had no effect on their fusion into multinucleated syncytialized cells. G-protein-linked S1P receptors 1, 2, and 3 were found in CTs by reverse transcriptase-polymerase chain reaction, and receptor 1 was found by Western blot analysis. Disruption of G_i signaling with pertussis toxin reversed the inhibitory effects of S1P. S1P reduced intracellular cAMP, and the addition of 8-bromo-cAMP reversed S1P inhibition of hCG secretion.

Therefore, we suggest that S1P inhibits the differentiation of CTs into STs through G_i-coupled S1P receptor interaction(s), leading to the inhibition of adenylate cyclase and reduced production of intracellular cAMP. This is the first reported effect of S1P on placental trophoblast function.

Supplementary key words sphingosine-1-phosphate receptors • adenosine 3',5'-cyclic monophosphate • chorionic gonadotropin • fusion • epidermal growth factor • G_i proteins

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

This article has been cited by other articles:

				X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system Hum. Reprod. Update, June 25, 2008; (2008) dmn023v2. [Abstract] [Full Text] [PDF]

				E. D. Johnstone, P. F. Speake, and C. P. Sibley Epidermal growth factor and sphingosine-1-phosphate stimulate Na+/H+ exchanger activity in the human placental syncytiotrophoblast Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2290 - R2294. [Abstract] [Full Text] [PDF]

				T. Kaneko-Tarui, L. Zhang, K. J Austin, L. E Henkes, J. Johnson, T. R Hansen, and J. K Pru Maternal and Embryonic Control of Uterine Sphingolipid-Metabolizing Enzymes During Murine Embryo Implantation Biol Reprod, October 1, 2007; 77(4): 658 - 665. [Abstract] [Full Text] [PDF]