Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During placental development cytotrophoblast stem cells fuse to form the syncytiotrophoblast, a multinucleate cytoplasm with a brush border in contact with the maternal blood. Biochemical differentiation including the expression of placental-specific proteins and hormones accompanies this maturation. However, the biochemical mechanisms responsible for these events are unknown. We have defined a system in which single cytotrophoblast-like cells of the human choriocarcinoma (BeWo) cell line undergo fusion and extensive morphological differentiation following their treatment with effectors of cyclic AMP metabolism. Forskolin incubation caused a dose-dependent increase in intracellular and secreted cyclic AMP and a coordinate fusion of cells which yielded syncytia containing hundreds of nuclei per cytoplasm and a mature dense "placental-like" brush border. These fused cells also synthesized and secreted large amounts of both subunits of chorionic gonadotropin. However, they continued to synthesize several other placenta-specific proteins--placental-like alkaline phosphatase, placental lactogen, and SP1--at rates similar to those in control cells. Other reported effectors of cyclic AMP metabolism also induced cell fusion, although theophylline, an inhibitor of phosphodiesterase, induced fusion by a cyclic AMP-independent mechanism. Additionally, unlike the case with forskolin, treatment of BeWo cells with theophylline did not induce other morphological features of mature syncytiotrophoblasts. Thus, this system will allow one to examine the biochemical mechanism of placental cell fusion in the absence of other variables of cell differentiation.
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PMID:Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. 215 59

Chronic ethanol (EtOH) use during pregnancy can be associated with fetal injury including the fetal alcohol syndrome (FAS). A contributing factor in this fetal injury may be the effect of EtOH on the placenta. In this study, we have examined the effect of in vitro EtOH treatment on adenosine 3':5'-cyclic monophosphate (cAMP) production by cultured trophoblasts, in response to various ligands. Epinephrine (10(-6) M) rapidly stimulated cAMP with a peak between 2.5 and 5 min, which gradually returned to basal levels over 3-4 hr. EtOH treatment for > 16 hr resulted in an up-regulation of epinephrine-stimulated cAMP production. Inhibition of phosphodiesterase with Rolipram enhanced the effect of EtOH on cAMP production, suggesting that the effect of EtOH treatment was not due to phosphodiesterase inhibition. In cultured trophoblasts, EtOH treatment increased both epinephrine and 16,16'-dimethylprostaglandin E2 (dm-PGE2)-dependent cAMP production at varying ligand concentrations, suggesting an increased capacity to respond. When trophoblasts were treated with forskolin, a stimulator of adenylyl cyclase, cAMP production was enhanced in EtOH-treated cells. This suggests that EtOH treatment enhances adenylyl cyclase activity in these intact, cultured cells. Unlike trophoblasts from term human placenta, JAR choriocarcinoma cells did not respond to epinephrine, adenosine, or dm-PGE2. The choriocarcinoma cells appeared to have lost the ability to respond to these ligands. Although the JAR cell adenylyl cyclase was stimulated by forskolin, EtOH treatment did not alter forskolin-stimulated cAMP production. In summary, EtOH-induced up-regulation of cAMP production appears to be cell specific, being present in normal human trophoblasts but not in undifferentiated choriocarcinoma cells.
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PMID:Ethanol enhancement of ligand-stimulated cAMP production by cultured human placental trophoblasts. 794 50

Ectonucleotide pyrophosphatase-phosphodiesterase 3 (ENPP3), a protein detected in the human uterus, has been found to play an important role in the development and invasion of tumours. It was recently discovered that ENPP3 was upregulated during the window of implantation in the human endometrium but its functional relevance remains elusive. The objective was to determine ENPP3 expression in human endometrium and its roles in endometrial receptivity and embryo implantation. ENPP3 expression was analysed using immunohistochemistry and western blot assay. The effects of ENPP3 on embryo implantation were evaluated using a BeWo cell (a human choriocarcinoma cell line) spheroid attachment assay and BeWo cells were dual cultured with Ishikawa cells transfected with lentiviral vectors (LV5-NC or LV5-ENPP3) to mimic embryo implantation in a Transwell model. The effects of endometrial ENPP3 on factors related to endometrial receptivity were also determined. The results showed that ENPP3 was expressed in human endometrial epithelial cells and its expression levels changed during the menstrual cycle, peaking in the mid-secretory phase, corresponding to the time of embryo implantation. The overexpression of endometrial ENPP3 not only increased the embryo implantation rate but also had positive effects on the expression of factors related to endometrial receptivity in human endometrial cells. The results indicate that ENPP3 levels undergo cyclic changes in the endometrium and affect embryo adhesion and invasion via altering the expression of implantation factors in the human endometrium. Therefore, ENPP3 may play an important role in embryo implantation and may be a unique biomarker of endometrial receptivity.
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PMID:Expression of ENPP3 in human cyclic endometrium: a novel molecule involved in embryo implantation. 2961 40