scholarly journals Bromoenol Lactone Promotes Cell Death by a Mechanism Involving Phosphatidate Phosphohydrolase-1 Rather than Calcium-independent Phospholipase A2

2003 ◽  
Vol 278 (45) ◽  
pp. 44683-44690 ◽  
Author(s):  
Lucía Fuentes ◽  
Rebeca Pérez ◽  
María L. Nieto ◽  
Jesús Balsinde ◽  
María A. Balboa
Keyword(s):  
Cell Death ◽  
Phospholipase A2 ◽  
Phosphatidate Phosphohydrolase ◽  
Bromoenol Lactone ◽  
Calcium Independent Phospholipase A2

Parathyroid hormone inhibits Na(+)-K(+)-ATPase through Gq/G11 and the calcium-independent phospholipase A2

1997 ◽  
Vol 272 (6) ◽  
pp. F781-F788 ◽  
Author(s):  
B. H. Derrickson ◽  
L. J. Mandel
Keyword(s):  
Arachidonic Acid ◽  
Parathyroid Hormone ◽  
Phospholipase A2 ◽  
Signaling Pathway ◽  
G Proteins ◽  
Proximal Tubules ◽  
Gtp Binding ◽  
Bromoenol Lactone ◽  
Acid Release ◽  
Calcium Independent Phospholipase A2

Previous studies from this laboratory have demonstrated that the 3–34 analog of parathyroid hormone (PTH) causes a 15–30% inhibition of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity in rat renal proximal tubules through the generation of an increase in intracellular arachidonic acid, followed by its conversion to 20-hydroxyeicosatetraenoic acid (20-HETE) [C. P. Ribeiro and L. J. Mandel. Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F209-F216, 1992; and C. P. Ribeiro, G. Dubay, J. R. Falk, and L. J. Mandel. Am. J. Physiol. 266 (Renal Fluid Electrolyte Physiol. 35): F497-F505, 1994]. The present study also uses proximal tubule suspensions to further elucidate this signaling pathway. Guanosine 5'-O-(2-thiodiphosphate), 500 microM, an inhibitor of heterotrimeric GTP-binding proteins (G proteins), and an anti-Gq/G11 antibody (1:500) both blocked the inhibition of the Na(+)-K(+)-ATPase by PTH-(3–34). Furthermore, a 42-kDa protein was identified in proximal tubules by the anti-Gq/G11 antibody (1:1,000). Bromoenol lactone (BEL), 1 microM, a suicide inhibitor of the calcium-independent 40-kDa phospholipase A2 (PLA2), prevented PTH-(3–34) inhibition of the Na(+)-K(+)-ATPase, unless exogenous 10 microM 20-HETE was added. In addition, BEL blocked the PTH-(3–34)-induced increase in arachidonic acid release in the proximal tubules. We conclude that a member of the Gq family and the calcium-independent 40-kDa PLA2 participate in the PTH-(3–34) signaling pathway in rat proximal tubules by mediating the steps between the binding of PTH-(3–34) to its receptor and the subsequent generation of arachidonic acid.

Bromoenol lactone, an inhibitor of Group V1A calcium-independent phospholipase A2 inhibits antigen-stimulated mast cell exocytosis without blocking Ca2+ influx

Cell Calcium ◽  
2007 ◽  
Vol 41 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Amanda Fensome-Green ◽  
Naina Stannard ◽  
Michelle Li ◽  
Stephen Bolsover ◽  
Shamshad Cockcroft
Keyword(s):  
Mast Cell ◽  
Phospholipase A2 ◽  
Bromoenol Lactone ◽  
Calcium Independent Phospholipase A2

Phospholipase A2 Enzymes Regulate αIIbβ3-mediated, but not FcγRII Receptor-mediated, pp125FAK Phosphorylation in Platelets

1999 ◽  
Vol 81 (04) ◽  
pp. 618-624 ◽  
Author(s):  
Beatrice Haimovich ◽  
Ping Ji ◽  
Ernest Ginalis ◽  
Ruth Kramer ◽  
Ralph Greco
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Platelet Adhesion ◽  
Specific Inhibitor ◽  
Cytosolic Calcium ◽  
Irreversible Inhibitor ◽  
Mobility Shift ◽  
Bromoenol Lactone ◽  
Calcium Independent Phospholipase A2 ◽  
Platelet Spreading

SummaryThe αIIbβ3 integrin and FcγRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca+2-sensitive cytosolic phospholipase A2 (cPLA2) but failed to trigger arachidonic acid (AA) release. Full mobility shift of cPLA2 and a massive release of AA release were stimulated by platelet adhesion to IgG or addition of thrombin to the fibrinogen adherent platelets. IgG and thrombin induced AA production were blocked by methyl arachidonyl fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and the Ca+2-independent phospholipase A2 (iPLA2). In contrast, bromoenol lactone (BEL), a specific inhibitor of iPLA2 had no effect on the release of AA. MAFP and BEL prevented pp125FAK phosphorylation and platelet spreading on fibrinogen having no effect on pp125FAK phosphorylation or platelet spreading on immobilized IgG. We conclude that αIIbβ3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PLA2 enzymes.Abbreviations: cPLA2, cytosolic calcium-dependent phospholipase A2; iPLA2, calcium-independent phospholipase A2; BSA, bovine serum albumin; mAB, monoclonal antibody; MAFP, methyl arachidonyl fluorophosphonate; pp125FAK, focal adhesion kinase; BEL, bromoenol lactone; AA, arachidonic acid.

Inhibition of mitochondrial calcium-independent phospholipase A2 (iPLA2) attenuates mitochondrial phospholipid loss and is cardioprotective

2002 ◽  
Vol 362 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Scott D. WILLIAMS ◽  
Roberta A. GOTTLIEB
Keyword(s):  
Infarct Size ◽  
Phospholipase A2 ◽  
Specific Inhibitor ◽  
Rabbit Heart ◽  
Adult Rabbit ◽  
Mitochondrial Fractions ◽  
Pathophysiological Role ◽  
Bromoenol Lactone ◽  
Calcium Independent Phospholipase A2 ◽  
And Function

Calcium-independent phospholipase A2 (iPLA2) is the predominant phospholipase A2 present in myocardium, and its pathophysiological role in acute myocardial infarction has been suggested by the rapid increase in membrane-associated iPLA2 activity during myocardial ischaemia and reperfusion (I/R). We therefore examined iPLA2 in mitochondrial fractions prepared from Langendorff-perfused adult rabbit hearts. Our studies indicate that iPLA2β is present in rabbit heart mitochondrial inner membranes with no apparent translocation during ischaemia, I/R or preconditioning. Mitochondrion-associated iPLA2 was catalytically competent and exhibited 2-, 3- and 2.5-fold increases in measured iPLA2 activity following ischaemia, I/R and preconditioning, respectively, when compared with the activity of iPLA2 measured in mitochondria from control hearts. Mitochondrial phospholipids are essential for maintaining the ordered structure and function of the organelle. I/R resulted in a rapid overall decrease in phosphatidylcholine and phosphatidylethanolamine glycerophospholipid species, as determined by electrospray ionization MS, that was partially alleviated by pretreatment of hearts with the iPLA2-specific inhibitor, bromoenol lactone (BEL). Pretreatment of I/R hearts with 10μM BEL significantly reduced the infarct size almost to that of continuously perfused hearts and was cardioprotective only when administered prior to ischaemia. Cardioprotection by BEL was reversed by the simultaneous perfusion of 100μM 5-hydroxydecanoate, implicating the mitochondrial KATP channel in BEL-mediated protection from I/R. Preconditioning also significantly reduced the infarct size in response to I/R but protection was lost by concurrent perfusion of 10μM arachidonic acid. Taken together, these data strongly implicate mitochondria-associated iPLA2 in the signal transduction of myocardial I/R injury.

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