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J. Lipid Res.
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A more recent version of this article appeared on February 1, 2008

Papers In Press, published online ahead of print November 16, 2007
J. Lipid Res., doi:10.1194/jlr.M700171-JLR200
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Submitted on April 6, 2007
Revised on October 26, 2007
Accepted on November 15, 2007

Lysophosphatidic acid and phosphatidic acid are differentially involved in autotaxin-, bacterial phospholipase D- and endogenous phospholipase D- dependent proliferation of ELT3 uterine leiomyoma cells

Emmanuelle Billon-Denis, Zahra Tanfin, and Philippe Robin

Université Paris Sud, IBBMC, Orsay cedex 91405

Corresponding Author: zahra.tanfin{at}u-psud.fr

Phospholipase D hydrolyses phosphatidylcholine into phosphatidic acid (PA), a lipidic mediator which may act directly on cellular proteins or may be metabolized into lysophosphatidic acid (LPA). We previously showed that PLD contributed to the mitogenic effect of endothelin-1 (ET-1) in a leiomyoma cell line (ELT3 cells). In this work we tested the ability of exogenous PA and PLD (scPLD), to reproduce the effect of endogenous PLD in ELT3 cells, and tested the possibility that these agents acted through LPA formation. We found that PA, scPLD and LPA stimulated thymidine incorporation. LPA and scPLD induced ERK1/2 MAP kinase activation. Using Ki16425, a LPA1/LPA3 receptors antagonist and siRNA targeting LPA1 receptor, we demonstrated that scPLD acted through LPA productionand LPA1 receptor activation. We found that scPLD induced LPA production by hydrolyzing lysophosphatidylcholine through its lysophospholipase D activity. Autotaxin, a naturally occurring lysophospholipase D, reproduced the effects of scPLD. By contrast, endogenous PLDstimulated by ET-1, failed to produce LPA. These results demonstrate that scPLD stimulated ELT3 cell proliferation by a LPA-dependent mechanism, different from that triggered by endogenous PLD. These data suggest that in vivo, an extracellular lysoPLD such as autotaxin may participate to leiomyoma growth through local LPA formation.


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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]




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