Prostaglandin Gbetagamma signaling stimulates gastrulation movements by limiting cell adhesion through Snai1a stabilization.

Gastrulation movements form the germ layers and shape them into the vertebrate body. Gastrulation entails a variety of cell behaviors, including directed cell migration and cell delamination, which are also involved in other physiological and pathological processes, such as cancer metastasis. Decreased Prostaglandin E(2) (PGE(2)) synthesis due to interference with the Cyclooxygenase (Cox) and Prostaglandin E synthase (Ptges) enzymes halts gastrulation and limits cancer cell invasiveness, but how PGE(2) regulates cell motility remains unclear. Here we show that PGE(2)-deficient zebrafish embryos, impaired in the epiboly, internalization, convergence and extension gastrulation movements, exhibit markedly increased cell-cell adhesion, which contributes to defective cell movements in the gastrula. Our analyses reveal that PGE(2) promotes cell protrusive activity and limits cell adhesion by modulating E-cadherin transcript and protein, in part through stabilization of the Snai1a (also known as Snail1) transcriptional repressor, an evolutionarily conserved regulator of cell delamination and directed migration. We delineate a pathway whereby PGE(2) potentiates interaction between the receptor-coupled G protein betagamma subunits and Gsk3beta to inhibit proteasomal degradation of Snai1a. However, overexpression of beta-catenin cannot stabilize Snai1a in PGE(2)-deficient gastrulae. Thus, the Gsk3beta-mediated and beta-catenin-independent inhibition of cell adhesion by Prostaglandins provides an additional mechanism for the functional interactions between the PGE(2) and Wnt signaling pathways during development and disease. We propose that ubiquitously expressed PGE(2) synthesizing enzymes, by promoting the stability of Snai1a, enable the precise and rapid regulation of cell adhesion that is required for the dynamic cell behaviors that drive various gastrulation movements.

Role of endoperoxides in arachidonic acid-induced vasoconstriction in the isolated perfused kidney of the rat.

1. Administration of arachidonic acid caused dose-dependent vasoconstriction in the isolated rat kidney perfused in situ with Krebs-Henseleit solution. 2. Inhibition of cyclo-oxygenase with indomethacin or meclofenamate reduced the renal vasoconstrictor effect of arachidonic acid. 3. The renal vasoconstrictor effect of arachidonic acid was unaffected by CGS-13080 at concentrations that effectively reduced thromboxane A2 (TxA2) synthesis by platelets and the kidney. 4. The endoperoxide/TxA2 receptor antagonist, SQ 29,548, abolished the renal vasoconstrictor effect of arachidonic acid and of U46619, an endoperoxide analogue. In contrast, SQ 29,548 did not affect the renal vasoconstrictor response to angiotensin II, prostaglandin E2 or F2 alpha. 5. These data suggest that the vasoconstrictor effect of arachidonic acid in the isolated kidney of the rat is mediated by its metabolites, including the prostaglandin endoperoxides.

[Effect of the hormonal environment on the human oocyte and its later development in vitro]. / Influence de l'environnement hormonal de l'ovocyte humain sur son évolution ultérieure in vitro.

The biosynthesis of progesterone by the granulosa cells that come from follicles from which the oocyte has been fertilized and has divided in vitro is far superior to that from the cells coming from follicles in which the oocyte has failed to develop. This result is in accordance with the raised levels of progesterone and the influence of androgens on lower levels of oestrogens in follicular fluid that evolved favourably. In the same follicles the ratio of concentrations of prostaglandins PGE2 to PGF2 alpha is twice as high as in the liquid from other follicles.

Biosynthesis and biological properties of prostaglandin endoperoxides and thromboxane A2.

Two prostaglandin endoperoxides, i. e. PGG2 and PGH2 were detected and isolated. They were unstable in aqueous medium (t1/2 at 37 degrees C about 5 min) and were converted to PGF2alpha by mild reducing agents. Human platelets as well as guinea pig lung and spleen converted the endoperoxides into thromboxane A2, an unstable (t1/2 at 37 degrees C about 30 s) oxetane/oxane derivative. Thromboxane A2 was converted into a stable hemiacetal derivative, thromboxane B2, by addition of 1 H2O. The two prostaglandin endoperoxides as well as thromboxane A2 caused platelet aggregation and the platelet release reaction. In addition they were potent stimulators of vascular and airway smooth muscle in vitro and in vivo.