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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotrophoblasts (from term placentae) and cells from the choriocarcinoma cell line JAr were cultivated either separately or in co-culture for 72 h. RNA was isolated from the cell cultures and Northern blots were developed using equal amounts of RNA. The RNA was hybridized with cDNA probes for CG alpha, CG beta and hPL. Corresponding m-RNAs were detected in the three RNAs except for hPL m-RNA which was absent from JAr cells RNA. The abundance of CG alpha and CG beta m-RNA in the RNA of the co-culture was higher than their accumulative abundances in the RNAs from cytotrophoblasts and JAr cells cultured alone and the abundance of hPL m-RNA in the RNA of the co-cultures was as high as that in the RNA from cytotrophoblasts cultured alone. On the basis of previous findings (Hochberg et al, 1991), it can be assumed that the cytotrophoblasts in the co-cultures are responsible for the increase in hormonal m-RNA production. It could be calculated that the abundances of the CG alpha, CG beta and hPL m-RNAs in the RNA which originated in the cytotrophoblast nuclei were 20, 100 and 10-fold higher respectively in the co-culture compared to those in the culture of cytotrophoblasts. This effect is limited to certain genes only as the concentration of the 92kD collagenase m-RNA and uPA (urokinase type plasminogen activator) m-RNA, which are both produced in cytotrophoblasts to a much higher extent than in JAr cells, and are not increased by cultivating the cytotrophoblasts with JAr cells in co-culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Placenta
PMID:Interaction between choriocarcinoma cell line (JAr) and human cytotrophoblasts in vitro. 768 96

We have investigated plasmin mediated proteolysis associated with trophoblast invasion during early stages of pregnancy in the rhesus monkey. In situ hybridization and immunocytochemical localization were used to define the cellular and tissue distribution of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and 2 (PAI-2) and urokinase receptor in early monkey placenta and uterus. Our results indicate: (1) uPA is expressed in proliferating and invasive cytotrophoblast located in chorionic villi as well as in extravillous trophoblast associated with uterine arterioles. This raises the possibility that urokinase may play an important role in trophoblast invasion. (2) PAI-1 mRNA is specifically localized in two areas where invasive trophoblast cells encounter maternal tissue directly. The extravillous cytotrophoblast cells at the maternofetal junction express PAI-1 mRNA. The invasive endovascular trophoblast cells within the uterine arterioles also express PAI-1 mRNA. The location sensitive expression of PAI-1 mRNA at the maternofetal junction may imply a protective function of this protease inhibitor that might be induced through interaction with decidual cells. (3) Urokinase receptor antigen has also been found at the maternofetal junction and in endovascular trophoblast cells of the invaded maternal blood vessel. (4) PAI-2 immunoreactivity is found in association with cytotrophoblast cells in anchoring choronic villi suggesting its association with early placentation. In conclusion, we propose that the plasmin/plasminogen activator system may not only regulate extracellular matrix degradation, but also modify migration and invasive behaviour of extravillous trophoblast cells, during early placentation.
Placenta
PMID:Expression of urokinase, plasminogen activator inhibitors and urokinase receptor in pregnant rhesus monkey uterus during early placentation. 1073 41

Changes in oxygen levels characterize normal and pathological human placentation. For example, relatively low Po(2)values are present around the blastocyst during implantation and in the placenta of the first trimester of pregnancy, a time of maximal trophoblast invasion. Our studies have revealed that low oxygen levels stimulate the in vitro invasiveness of cultured first trimester trophoblasts. This increased invasive ability is linked to elevated expression of some components of the plasminogen activator system and requires the participation of a putative haem protein. As gestation proceeds beyond the first trimester, and the extent of trophoblast invasion decreases, placental oxygen levels rise with a corresponding increase in blood flow. However, during certain pathological conditions, such as pre-eclampsia/intrauterine growth restriction, impaired remodelling of the uterine spiral arterioles leads to vessels with reduced diameters and localized regions of placental ischaemia/hypoxia. Placental hypoxia in the second half of gestation, as a consequence of reduced uteroplacental blood flow, may result in aberrant expression of genes that contribute to the pathophysiology of pre-eclampsia. Some of these genes encode certain cytokines and vasoactive molecules. We have also identified other genes whose expression is regulated by oxygen. Expression of one of them is induced in trophoblast and other cell types cultured under low oxygen levels and the product of the gene is a 43-kDa protein which we have termed PROXY-1. Compared to placental tissues and membranes isolated from uncomplicated pregnancies, PROXY-1 expression is elevated in tissues from pre-eclamptic pregnancies such as chorionic villi of peri-infarct regions, basal plate and membrane decidua, as well as chorion. Overall, these observations suggest that oxygen levels play an important role in placentation and in the pathophysiology of certain complications of pregnancy.
Placenta
PMID:Adriana and Luisa Castellucci award lecture 1999: role of oxygen in the regulation of trophoblast gene expression and invasion. 1094 Jan 94

Plasminogen activators and inhibitors may be important early in primate implantation but evidence for this is sparse in non-human primates. We define the expression of urokinase type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and type 2 (PAI-2), the receptor for uPA (uPAR) and fibrin/fibrinogen in monkey implantation sites. In situ hybridization and immuno-histochemical localization of rhesus monkey implantation sites (day 15-16 postovulation) indicate: (1) uPA mRNA is localized to placental trophoblast, epithelial plaque and endometrial stroma. (2) tPA mRNA is mainly expressed in glandular cells of endometrium. (3) PAI-1 expression is linked to a specific population of trophoblasts that confront maternal cells, adding support to our view that it has a regulatory role in trophoblast invasion. (4) Localization of tPA antigen confirms that uterine glands are the major source of tPA and that it is also closely associated with fibrin(ogen) suggesting its possible function during implantation is fibrinolysis. (5) Unlike uPA mRNA, however, the distribution of uPA protein and its cell surface receptor uPAR suggests that it mediates trophoblast invasion and plays a significant role in angiogenesis. (6) PAI-2, the inhibitor associated with pregnancy in humans, was found in unidentified cells located specifically along the maternofetal junction. This localization adjacent to areas of cell death at the maternofetal junction implies that it may have a role as a protective curtain with anti-apoptotic function. In conclusion our results suggest that gene expression of PAs and PAIs in early implantation sites are tissue-specific, location-sensitive and function-related.
Placenta
PMID:Plasminogen activators and inhibitors are transcribed during early macaque implantation. 1117 Aug 23

In order to clarify the possible interactions between nitric oxide (NO) and arachidonic acid (AA) pathways, human amnion-like WISH cells were perifused to measure the effects of the following substances on [(3)H]arachidonic acid release: (1) sodium nitroprusside (SNP), a nitric oxide donor; (2) 1,1,1-trifluoromethyl-6,9,12,15-heicosatetraen-2-one, a cytosolic phospholipase A(2) (cPLA(2)) inhibitor; (3)L -arginine, the substrate of nitric oxide synthase (NOS); (4) 3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole and 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, activator and inhibitor of soluble guanylyl cyclase, respectively; (5) a membrane-permeable non-hydrolyzable analogue of guanosine-3',5'-cyclic monophosphate (cGMP). Furthermore, the effect of SNP on prostaglandin E(2) (PGE(2)) release was tested. Exogenous and endogenous NO, as well as the guanylyl cyclase activator and cGMP analogue, significantly increased [(3)H]arachidonic acid release. Both soluble guanylyl cyclase and PLA(2) inhibitors counteracted SNP response. Exogenous NO increased PGE(2) release, although to a much lesser degree compared with arachidonic acid release. Our results indicate that NO stimulates AA release in WISH cells by activating PLA(2) through a cyclic GMP-dependent mechanism.
Placenta
PMID:Effect of nitric oxide on arachidonic acid release from human amnion-like WISH cells. 1236 77

Phospholipase D (PLD) is present in human placental tissue. Since purinergic receptor agonists activate PLD in many different cell types, we evaluated the purinergic activation of the enzyme in cultured trophoblasts from the placenta. We found that P(2) receptor agonists stimulate PLD. The preferred ligand for P(2X7) (P(2Z)) receptor subtype, BzBz-ATP (10(-3)M ), induced the enzyme more than ten times over basal (unstimulated) activity, while ATP caused a much smaller increase. ATPgammaS, ADP and UTP were even less effective, compared to BzBz-ATP or ATP. AMP and alpha,beta-methyl-ATP, a P(2X) agonist that is uniquely inactive on the P(2X7) subtype, had no effect. This represents the first suggestion of the presence of the P(2X7) type of receptor in human trophoblasts that was directly confirmed by immunoblot detection. The action of BzBz-ATP was dependent upon the presence of calcium in the culture medium and was inhibited by high (5m M ) Mg(++) concentration. P(2X7) receptor subtype specific antagonists, ATP-2',3'-dialdehyde (o-ATP), CBB and the broad specificity P(2) inhibitor PPADS inhibited the effect of BzBz-ATP. Pertussis toxin treatment did not inhibit the effect. Down-regulation of cPKC/nPKC isoforms by prolonged PMA treatment (36 h, 10(-7)M ) prevented the stimulation of PLD by P(2) agonists or the calcium ionophore A-23187. PLA(2) inhibitors did not block the effect of BzBz-ATP. The possibility for a calcium influx related interdependence of PLC and PLD was evaluated. For PLC activation, UTP and ATP surpassed BzBz-ATP, while ionophore did not elevate PLC (assessed by IP(3) measurements). This suggested the predominance of a P(2Y2) receptor in the whole cell in gross activation of PLC. PLD was affected with a reversed order of potency. These results and the dependence of PLD on PKC activity implies that a restricted, membrane localized calcium flux activates PKC and in turn, mediates the P(2X7) dependent stimulation of PLD. This may have implications for physiologic regulation of trophoblast function.
Placenta
PMID:Regulation of phospholipase D in human placental trophoblasts by the P(2) purinergic receptor. 1236 78

Plasminogen activator inhibitor (PAI)-1 plays a key role in the regulation of fibrinolysis and cellular invasion by virtue of suppression of plasminogen activator function. Excessive production of placental PAI-1 has been associated with aberrant periplacental fibrin deposition in pregnancies complicated by pre-eclampsia (PE) and intrauterine growth restriction (IUGR). In the current study we used HTR-8/SVneo cells and primary cultures of cytotrophoblasts as models for study of PAI-1 regulation by transforming growth factor (TGF)-beta, and dexamethasone (DEX), a synthetic glucocorticoid (GC). ELISA and Northern blotting assays revealed that DEX treatment significantly enhanced TGF-beta effects on PAI-1 protein and mRNA expression in HTR-8/SVneo cells and cytotrophoblasts. These effects were GC-specific in that DEX and cortisol, but not estradiol, progesterone or testosterone, augmented PAI-1 levels in TGF-beta-treated cells. Conversely, DEX and TGF-beta treatment suppressed PAI-2 levels in HTR-8/SVneo cells and did not affect PAI-2 levels in cytotrophoblasts. PAI-1 promoter assays revealed that TGF-beta, but not DEX, enhanced PAI-1 expression in HTR-8/SVneo cells through a transcriptional mechanism. These results suggest that GC and TGF-beta may alter fibrinolytic and invasive properties of trophoblasts through their effects on PAI-1 expression.
Placenta 2002 Nov
PMID:Regulation of plasminogen activator inhibitor (PAI)-1 expression in a human trophoblast cell line by glucocorticoid (GC) and transforming growth factor (TGF)-beta. 1239 12

Decidual acute atherosis is associated with pre-eclampsia, but the underlying mechanism is still unclear. We have previously demonstrated elevated level of the oxidative stress marker 8-isoprostaglandin F(2 alpha)(8-isoprostane) and lipids in pre-eclamptic decidual tissue. Arachidonic acid (AA) in tissue phospholipids is a source for 8-isoprostane generation, and 8-isoprostane is liberated from tissue phospholipids by phospholipase A(2)(PLA(2)). The aims of this study were to explore whether AA content or PLA(2)expression in pre-eclamptic decidual tissue differed from controls. Decidua basalis tissues were obtained by vacuum aspiration at Caesarean delivery in pre-eclamptic and control pregnancies. We demonstrated a statistically significantly higher total PLA(2)activity in pre-eclamptic decidua compared to control tissue. On the other hand, no differences in AA content of tissue phospholipids or protein expression of secretory and cytosolic PLA(2)between pre-eclamptic and control decidual tissue were found. In conclusion, the elevated level of free 8-isoprostane in pre-eclamptic decidual tissue could be caused by augmented PLA(2)activity. We speculate that an elevated PLA(2)enzyme activity in pre-eclamptic decidual tissue could be of importance in the pathogenesis of 'acute atherosis', comparable to the atherogenesis in cardiovascular diseases.
Placenta 2003 Nov
PMID:Augmented PLA2 activity in pre-eclamptic decidual tissue--a key player in the pathophysiology of 'acute atherosis' in pre-eclampsia? 1458 Mar 79

Increased prostaglandin E(2)(PGE(2)) synthesis involves multiple enzymes and two isoforms of the terminal enzyme of this biosynthetic pathway, PGE synthase (PGES), were recently identified. Cytosolic PGES (cPGES) is identical to the Hsp90 chaperone, p23, and is reportedly functionally coupled to constitutive PG endoperoxide H synthase-1 (PGHS-1). Microsomal PGES (mPGES), on the other hand, is inducible by proinflammatory cytokines such as IL-1beta. We have studied the cellular localization of both enzyme isoforms in human placenta at term and early gestation (10 weeks). Cytosolic PGES was immunolocalized to the fibroblasts and macrophages in villous stroma, whereas mPGES was localized in the extravillous trophoblasts (EVTs) as well as macrophages in both term and early gestation tissues. Microsomal PGES was also observed in cytotrophoblasts (CTs), but not in syncytiotrophoblasts (STs), in early gestation. Apoptotic early gestational STs were heavily stained with cPGES. We also investigated the cellular localization of cPLA(2)and PGHS-2 in early gestation and at term. Cytosolic PLA(2)was immunolocalized to the stroma and STs at term, but was only observed in CTs in early gestation. PGHS-2, on the other hand, was immunolocalized to both extravillous and STs in early gestation and at term. Our results suggest that mPGES could play a role in trophoblast invasion via its association with EVTs in the basal plate, whereas cPGES could be involved in apoptosis or repair mechanisms.
Placenta 2004 Apr
PMID:Differential localization of prostaglandin E synthase isoforms in human placental cell types. 1502 17

Phospholipid-derived mediators, inflammatory cytokines and extracellular matrix remodelling enzymes are all involved in the initiation of human labour and delivery. We have previously demonstrated that natural and synthetic PPAR-gamma ligands regulate LPS-stimulated pro-inflammatory cytokine release from human gestational tissues, however, the effect of these ligands on the basal and/or LPS-induced expression of prostaglandins and proteases is not known. Therefore, the aim of this study was to determine the effects of 15d-PGJ(2) and troglitazone on the expression of basal and LPS-stimulated inflammatory mediators in human gestational tissues. Human placenta, amnion and choriodecidua (n=5) were incubated in the presence or absence of 15 microM 15d-PGJ(2) and 30 microM troglitazone under basal and LPS-stimulated (10 microg/ml) conditions. Treatment of placenta, amnion and choriodecidua with both 15d-PGJ(2) and troglitazone decreased basal and LPS-stimulated IL-1beta, IL-6, IL-10 and TNF-alpha release. Basal type II PLA(2) release from placental tissues was also significantly decreased by 15d-PGJ(2) and troglitazone. There was no effects of 15d-PGJ(2) and troglitazone on cPLA(2) protein expression. Both 15d-PGJ(2) and troglitazone significantly decreased basal and LPS-stimulated PGE(2) and PGF(2alpha) release from placenta and amnion. However, in choriodecidua, although 15d-PGJ(2) decreased basal and/or LPS-stimulated PGE(2) and PGF(2alpha) release, there was an increase in PGE(2) and PGF(2alpha) release in the presence of troglitazone. 15d-PGJ(2) and troglitazone inhibited MMP-9 release from human amnion. NF-kappaB DNA binding activity and NF-kappaB p65 protein expression was inhibited by treatment with 15d-PGJ(2) in human amnion. There was no effect of 15d-PGJ(2) or troglitazone on PPAR-gamma protein, and GW9662 failed to alleviate 15d-PGJ(2) and troglitazone inhibition of IL-6 and TNF-alpha release in placenta, amnion and choriodecidua. The data demonstrated in this study suggest that the 15d-PGJ(2) and troglitazone exhibit anti-inflammatory properties in human gestational tissues via PPAR-gamma independent actions.
Placenta
PMID:15-Deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone regulation of the release of phospholipid metabolites, inflammatory cytokines and proteases from human gestational tissues. 1643 95


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