Identification of Calcium-independent Phospholipase A2 (iPLA2) β, and Not iPLA2γ, as the Mediator of Arginine Vasopressin-induced Arachidonic Acid Release in A-10 Smooth Muscle Cells

Jenkins, Christopher M.; Han, Xianlin; Mancuso, David J.; Gross, Richard W.

doi:10.1074/jbc.m202568200

Cited by 167 publications

(201 citation statements)

References 58 publications

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“…The majority of immunoreactive protein for both isoforms was detected in the cytosol (Figure 4). A recent manuscript has described the selective inhibition of iPLA 2 β and iPLA 2 γ using the S-and R-enantiomers of BEL respectively [19]. We incubated the cytosolic fraction from human platelets with increasing concentrations of (R)-BEL, (S)-BEL or racemic BEL for 10 minutes prior to assay of iPLA 2 activity ( Figure 5).…”

Section: Resultsmentioning

confidence: 99%

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Phospholipase A2-catalyzed hydrolysis of plasmalogen phospholipids in thrombin-stimulated human platelets

Beckett

Kell

Creer

et al. 2007

Thrombosis Research

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In the present study, phospholipase A 2 (PLA 2 )-catalyzed hydrolysis of platelet membrane phospholipids was investigated by measuring PLA 2 activity, phospholipid hydrolysis, arachidonic acid release and choline lysophospholipid production in thrombin-stimulated human platelets. Thrombin-stimulated platelets demonstrated selective hydrolysis of arachidonylated plasmenylcholine and plasmenylethanolamine, with little change in diacyl phospholipids. Accelerated plasmalogen hydrolysis was accompanied by increased arachidonic acid and thromboxane B 2 release and increased lysoplasmenylcholine production. Thrombin stimulation caused an increase in PLA 2 activity measured in the cytosolic fraction with plasmenylcholine only; no increase in activity was measured with phosphatidylcholine. No change in membrane-associated PLA 2 activity was observed with either substrate tested. Pretreatment with the Ca 2+ -independent PLA 2 -selective inhibitor, bromoenol lactone, inhibited completely any thrombin-stimulated phospholipid hydrolysis. Thus, thrombin stimulation of human platelets activates a cytosolic PLA 2 that selectively hydrolyzes arachidonylated plasmalogen phospholipids.

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Section: Resultsmentioning

confidence: 99%

“…This isoform has recently been identified and characterized [7] and has been found to be uniquely sensitive to (R)-BEL [19]. Human iPLA 2 -γ has multiple alternative start sites for translation resulting in functional PLA 2 γ proteins with MW of 63-, 74-, 77-and 88-kDa [7].…”

Section: Discussionmentioning

confidence: 99%

Phospholipase A2-catalyzed hydrolysis of plasmalogen phospholipids in thrombin-stimulated human platelets

Beckett

Kell

Creer

et al. 2007

Thrombosis Research

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“…For iPLA 2 ␤, several important signaling functions have been suggested, including its role in agonist-induced stimulation of smooth muscle (20) and endothelial cells (21), in lymphocyte proliferation (22), and in endothelium-dependent vascular relaxation (21). Very recently, it was reported that myocardial ischemia activates iPLA 2 ␤ in intact myocardium, and that iPLA 2 ␤ activation is sufficient to induce malignant ventricular arrhythmias (23).…”

Section: Discussionmentioning

confidence: 99%

“…iPLA 2 has been shown to be implicated in many cellular functions ranging from basal fatty acid reacylation reactions (17), to playing major roles in intracellular signaling cascades, including its involvement in agonist-induced eicosanoid production (18,19), stimulation of smooth muscle (20) and endothelial cells (21), in lymphocyte proliferation (22), and in endothelium-dependent vascular relaxation (21). Very recently, it has been reported that myocardial ischemia activates iPLA 2 ␤ in intact myocardium, and that this iPLA 2 ␤ activation is sufficient to induce malignant ventricular arrhythmias (23), and also that functional iPLA 2 is required for activation of store-operated channels and capacitative Ca 2ϩ influx in several cell types (24).…”

mentioning

confidence: 99%

FcγRI-triggered Generation of Arachidonic Acid and Eicosanoids Requires iPLA2 but Not cPLA2 in Human Monocytic Cells

Tay¹,

Melendez

2004

Journal of Biological Chemistry

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Aggregation of receptors for immunoglobulin G (Fc␥Rs) on myeloid cells activates a series of events that are key in the inflammatory response and that can ultimately lead to targeted cell killing by antibody-directed cellular cytotoxicity. Generation of lipid-derived proinflammatory mediators is an important component of the integrated cellular response mediated by receptors for the constant region of immunoglobulins (Fc). We have demonstrated previously that, in interferon-␥-primed U937 cells, the high affinity receptor for IgG, Fc␥RI, is coupled to a novel intracellular signaling pathway that involves the sequential activation of phospholipase D, sphingosine kinase, calcium transients, and protein kinase C isoforms, leading to the activation of the NADPHoxidative burst. Here, we investigate the nature of the phospholipase that regulates arachidonic acid and eicosanoid production. Our data show that Fc␥RI couples to iPLA 2 ␤ for the release of arachidonic acid and the generation of leukotriene B 4 and prostaglandin E 2 . Activation of iPLA 2 ␤ was protein kinase C-dependent; on the other hand, platelet-activating factor triggered cPLA 2 ␣ by means of the mitogen-activated protein kinase pathway. These studies demonstrate that intracellular PLA 2 s can be selectively regulated by different stimuli and suggest a critical role for iPLA 2 ␤ in the intracellular signaling cascades initiated by Fc␥RI and its functional role in the generation of key inflammatory mediators.

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“…Cytosolic iPLA 2 (Group VIA-1 and VIA-2 PLA 2 ) are suggested to me-diate ischemia-induced myocardial dysfunction (13), cAMP release in rat mesangial cells (14), arginine vasopressin-induced arachidonic acid release in A-10 smooth muscle cells (15), and nuclear phospholipid mass decreases after myocardial ischemia (16). However, the exact mechanisms controlling cytosolic iPLA 2 , such as Group VIA-1 and VIA-2 PLA 2 , in these processes and the exact phospholipids involved are not known.…”

mentioning

confidence: 99%

Inactivation of Endoplasmic Reticulum Bound Ca2+-Independent Phospholipase A2 in Renal Cells during Oxidative Stress

Cummings¹,

Gelasco

Kinsey³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. The purpose of this study was to determine the actions of oxidants on endoplasmic reticulum bound Ca 2ϩ -independent phospholipase A 2 (ER-iPLA 2 ) and phospholipids in renal cells. Exposure of renal proximal tubule cells (RPTC) to the oxidants tert-butyl hydroperoxide (TBHP), cumene hydroperoxide, and cisplatin resulted in time-and concentrationdependent decreases in the activity of ER-iPLA 2 . TBHP-induced ER-iPLA 2 inactivation was reversed by the addition of dithiothreitol to microsomes isolated from treated RPTC. TBHP also directly inactivated ER-iPLA 2 in microsomes isolated from untreated RPTC. Similar to RPTC, dithiothreitol prevented TBHP-induced ER-iPLA 2 inactivation in microsomes as did the reactive oxygen scavengers butylated hydroxytoluene and N,N'-diphenyl-p-phenylenediamine and the iron chelator deferoxamine. Electron paramagnetic resonance spin trapping demonstrated that TBHP initiated a carbon-centered radical after 1 min of exposure in microsomes, preceding ER-iPLA 2 inactivation, and further studies suggested that the formation of the carbon-centered radical species occurred after or in concert with the formation of oxygen-centered radicals. Phospholipid content was determined after TBHP exposure in the presence and absence of the ER-iPLA 2 inhibitor bromoenol lactone. Treatment of RPTC with TBHP resulted in 35% decreases in (16:0, 20:4)-phosphatidylethanolamine (PtdEtn), (18:0, 18:1)-plasmenylethanolamine (PlsEtn), a 30% decrease in (16:0, 18:3)-phosphatidylcholine (PtdCho), and a 25% decrease in (16:0, 20:4)-phosphatidylcholine (PtdCho). In contrast, treatment of RPTC with bromoenol lactone before TBHP exposure decreased the content of 11 phospholipids, decreasing a majority of PlsEtn phospholipids 60%, and 4 of the 8 PlsCho phospholipids 40%, while PtdCho and PtdEtn were marginally affected compared with TBHP. These data demonstrate that ER-iPLA 2 is inactivated by oxidants, that the mechanism of inactivation involves the oxidation of ER-iPLA 2 sulfhydryl groups, and that ER-iPLA 2 inhibition increases oxidant-induced RPTC phospholipid loss.Phospholipase A 2 (PLA 2 ) are esterases that cleave glycerophospholipids at the sn-2 position, resulting in the release of a fatty acid and a lysophospholipid (1). To date, over 19 different types of PLA 2 exist, differing in size, localization, and Ca 2ϩ requirement (2,3). Within the last 4 yr, a number of novel Ca 2ϩ -independent PLA 2 (iPLA 2 ) isoforms have been identified. Ma et al.

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Identification of Calcium-independent Phospholipase A2 (iPLA2) β, and Not iPLA2γ, as the Mediator of Arginine Vasopressin-induced Arachidonic Acid Release in A-10 Smooth Muscle Cells

Cited by 167 publications

References 58 publications

Phospholipase A2-catalyzed hydrolysis of plasmalogen phospholipids in thrombin-stimulated human platelets

Phospholipase A2-catalyzed hydrolysis of plasmalogen phospholipids in thrombin-stimulated human platelets

FcγRI-triggered Generation of Arachidonic Acid and Eicosanoids Requires iPLA2 but Not cPLA2 in Human Monocytic Cells

Inactivation of Endoplasmic Reticulum Bound Ca2+-Independent Phospholipase A2 in Renal Cells during Oxidative Stress

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