scholarly journals Secretory and cytosolic phospholipase A2 activities and expression are regulated by oxytocin and estradiol during labor

Reproduction ◽  
2007 ◽  
Vol 134 (2) ◽  
pp. 355-364 ◽  
Author(s):  
Mariana Gabriela Farina ◽  
Silvia Billi ◽  
Gustavo Leguizamón ◽  
Carina Weissmann ◽  
Tamara Guadagnoli ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Estrogen Receptors ◽  
Steroid Hormones ◽  
Cytosolic Phospholipase A2 ◽  
Ovarian Steroid ◽  
Rat Uterus ◽  
Cytosolic Phospholipase ◽  
17Β Estradiol

The release of arachidonic acid from membrane glycerophospholipids through the action of phospholipases (PLs) is the first step in the biosynthesis of prostaglandins (PGs). In reproductive tissues, the most important PLs are cytosolic PLA2(cPLA2) and types IIA and V of the secretory isoform (sPLA2). The aim of this work was to investigate the role of ovarian steroid hormones and oxytocin (OT) in the regulation of rat uterine PLA2activity and expression during pregnancy and labor. The activity of sPLA2increased near labor, whereas cPLA2activity augmented towards the end of gestation. The levels of sPLA2IIA and cPLA2mRNA showed an increase before labor (P<0.05, day 21), whereas sPLA2V mRNA was not regulated during pregnancy. The administration of atosiban (synthetic OT antagonist) together with tamoxifen (antagonist of estrogen receptors) was able to decrease cytosolic and secretory PLA2activities, diminish the expression of sPLA2IIA and cPLA2, as well as decrease PGF2αproduction before the onset of labor (P<0.01). The ovarian steroid did not affect PLA2during pregnancy. Collectively, these findings indicate that in the rat uterus, both 17β-estradiol and OT could be regulating the activity and the expression of the secretory and the cytosolic isoforms of PLA2, thus controlling PGF2αsynthesis prior to the onset of labor.

scholarly journals Involvement of cytosolic phospholipase A2, and the subsequent release of arachidonic acid, in signalling by Rac for the generation of intracellular reactive oxygen species in Rat-2 fibroblasts

2000 ◽  
Vol 348 (3) ◽  
pp. 525-530 ◽  
Author(s):  
Chang-Hoon WOO ◽  
Zee-Won LEE ◽  
Byung-Chul KIM ◽  
Kwon-Soo HA ◽  
Jae-Hong KIM
Keyword(s):  
Reactive Oxygen Species ◽  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Active Form ◽  
Reactive Oxygen ◽  
Cytosolic Phospholipase A2 ◽  
Signalling Pathway ◽  
Oxygen Species ◽  
Cytosolic Phospholipase

Although there have been a number of recent studies on the role of Rac in the generation of reactive oxygen species (ROS), details of the signalling pathway remain unclear. In the present study we analysed the extent to which the activation of cytosolic phospholipase A2 and the resultant release of arachidonic acid (AA) are involved in the Rac-mediated generation of ROS. Transfection of Rat-2 cells with RacV12, a constitutively active form of Rac1, induced elevated levels of ROS, as reflected by increased H2O2-sensitive fluorescence of 2ʹ,7ʹ-dichlorofluorescein. These effects could be blocked by inhibiting phospholipase A2 or 5-lipoxygenase but not by inhibiting cyclo-oxygenase. The application of exogenous AA increased levels of ROS but the effect was dependent on the further metabolism of AA to leukotrienes C4/D4/E4 by 5-lipoxygenase. Indeed, the exogenous application of a mixture of leukotrienes C4/D4/E4 elicited transient elevations in the levels of ROS that were blocked by catalase. These findings indicate that phospholipase A2 and subsequent AA metabolism by 5-lipoxygenase act as downstream mediators in a Rac signalling pathway leading to the generation of ROS.

scholarly journals Role of Phosphorylation Sites and the C2 Domain in Regulation of Cytosolic Phospholipase A2

1999 ◽  
Vol 145 (6) ◽  
pp. 1219-1232 ◽  
Author(s):  
Miguel A. Gijón ◽  
Diane M. Spencer ◽  
Alan L. Kaiser ◽  
Christina C. Leslie
Keyword(s):  
Arachidonic Acid ◽  
Nuclear Envelope ◽  
Phospholipase A2 ◽  
Okadaic Acid ◽  
Cytosolic Phospholipase A2 ◽  
Phosphorylation Sites ◽  
C2 Domain ◽  
Arachidonic Acid Release ◽  
Cytosolic Phospholipase ◽  
Acid Release

Cytosolic phospholipase A2 (cPLA2) mediates agonist-induced arachidonic acid release, the first step in eicosanoid production. cPLA2 is regulated by phosphorylation and by calcium, which binds to a C2 domain and induces its translocation to membrane. The functional roles of phosphorylation sites and the C2 domain of cPLA2 were investigated. In Sf9 insect cells expressing cPLA2, okadaic acid, and the calcium-mobilizing agonists A23187 and CryIC toxin induce arachidonic acid release and translocation of green fluorescent protein (GFP)-cPLA2 to the nuclear envelope. cPLA2 is phosphorylated on multiple sites in Sf9 cells; however, only S505 phosphorylation partially contributes to cPLA2 activation. Although okadaic acid does not increase calcium, mutating the calcium-binding residues D43 and D93 prevents arachidonic acid release and translocation of cPLA2, demonstrating the requirement for a functional C2 domain. However, the D93N mutant is fully functional with A23187, whereas the D43N mutant is nearly inactive. The C2 domain of cPLA2 linked to GFP translocates to the nuclear envelope with calcium-mobilizing agonists but not with okadaic acid. Consequently, the C2 domain is necessary and sufficient for translocation of cPLA2 to the nuclear envelope when calcium is increased; however, it is required but not sufficient with okadaic acid.

Evidence for a Role for Phospholipase C, but not Phospholipase A2, in Platelet Activation in Response to Low Concentrations of Collagen

2001 ◽  
Vol 85 (05) ◽  
pp. 882-889 ◽  
Author(s):  
Leslie Lockhart ◽  
Caroline Pampolina ◽  
Brent Nickolaychuk ◽  
Archibald McNicol
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Phospholipase C ◽  
Platelet Activation ◽  
Cytosolic Phospholipase A2 ◽  
Arachidonic Acid Release ◽  
Cytosolic Phospholipase ◽  
Low Concentrations ◽  
Acid Release ◽  
Induced Aggregation

SummaryThe release of arachidonic acid is a key component in platelet activation in response to low concentrations (1-20 g/ml) of collagen. The precise mechanism remains elusive although a variety of pathways have been implicated. In the present study the effects of inhibitors of several potentially key enzymes in these pathways have been examined. Collagen (1-10 g/ml) caused maximal platelet aggregation which was accompanied by the release of arachidonic acid, the synthesis of thromboxane A2, and p38MAPK phosphorylation. Preincubation with the dual cyclooxygenase/lipoxygenase inhibitor BW755C inhibited aggregation and thromboxane production, and reduced p38MAPK phosphorylation. A phospholipase C inhibitor, U73122, blocked collagen-induced aggregation and reduced arachidonic acid release, thromboxane synthesis and p38MAPK phosphorylation. Pretreatment with a cytosolic phospholipase A2 inhibitor, AACOCF3, blocked collagen-induced aggregation, reduced the levels of thromboxane formation and p38MAPK phosphorylation but had no significant effect on arachidonic acid release. In contrast inhibition of PKC by Rö31-8220 inhibited collagen-induced aggregation, did not affect p38MAPK phosphorylation but significantly potentiated arachidonic acid release and thromboxane formation. Collagen caused the tyrosine phosphorylation of phospholipase C 2 which was inhibited by pretreatment with U73122, unaffected by AACOCF3 and enhanced by Rö31-8220. These results suggest that cytosolic phospholipase A2 plays no role in the arachidonic acid release in response to collagen. In contrast, the data are consistent with phospholipase C 2 playing a role in an intricately controlled pathway, or multiple pathways, mediating the release of arachidonic acid in collagen-stimulated platelets.

Downregulation of nitric oxide formation by cytosolic phospholipase A2-released arachidonic acid

2004 ◽  
Vol 36 (3) ◽  
pp. 319-329 ◽  
Author(s):  
Letizia Palomba ◽  
Marzia Bianchi ◽  
Tiziana Persichini ◽  
Mauro Magnani ◽  
Marco Colasanti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Cytosolic Phospholipase A2 ◽  
Oxide Formation ◽  
Nitric Oxide Formation ◽  
Cytosolic Phospholipase
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