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Am J Physiol Cell Physiol (May 14, 2003). doi:10.1152/ajpcell.00040.2003
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Submitted on January 28, 2003
Accepted on April 30, 2003

A critical role for PKC {zeta} in endothelin-1-induced uterine contractions at the end of pregnancy

G Di Liberto1, E Dallot1, I Eude-Le Parco1, D Cabrol2, F Ferre1, and M Breuiller-Fouche1*

1 u361, INSERM, Paris, France; Rene Descartes, University, Paris, France
2 Hopital Cochin, AP-HP, Paris, France

* To whom correspondence should be addressed. E-mail: breuiller-fouche{at}cochin.inserm.fr.

We have previously shown that protein kinase C (PKC){zeta} and/or PKC{delta} are necessary for endothelin-1 (ET-1)-induced human myometrial contraction at the end of pregnancy (Eude I, Paris P, Cabrol D, Ferre F and Breuiller-Fouche M, Biol Reprod 2000. 63:1567). Here we report that the selective inhibitor of PKC{delta} isoform, Rottlerin, does not prevent ET-1-induced contractions, whereas LY294002, a phosphatidylinositol (PI) 3-kinase inhibitor, affects the contractile response. This study characterized the in vitro contractile response of cultured human pregnant myometrial cells to ET-1 known to induce in vitro contractions of intact uterine smooth muscle strips. Cultured myometrial cells incorporated into collagen lattices have the capacity to reduce the size of these lattices, referred as lattices contraction. Neither the selective cPKC isoform inhibitor, Go 6976, nor Rottlerin affected myometrial cell-mediated gel contraction by ET-1 whereas this effect was blocked by LY294002. We found that treatment of myometrial cell lattices with an inhibitory peptide specific for PKC{zeta} or with an antisense against PKC{zeta} resulted in a significant lost of ET-1-induced contraction. Evidence is also presented, using confocal microscopy, that ET-1 induced translocation of PKC{zeta} to a structure coincident with the actin-rich micro-filaments of the cytoskeleton. We have shown that PKC{zeta} has a role in the actin organization in ET-1-stimulated cells. Accordingly, our results suggest that PKC{zeta} play a role in myometrial contraction of pregnant women.




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