the enzyme harbors a consensus motif common to members of the GVIA-iPLA2 subfamily, the group VIA phospholipase A2 (GVIA-iPLA2) subfamily of enzymes functions independently of calcium within the cytoplasm of cells. The Caenorhabditis elegans genome encodes multiple putative GVIAiPLA2 isoforms
inhibition of cPLA2 abolishes release of arachidonate but not palmitate from cells treated with fetal bovine serum. Inhibition of PLA2 precludes fetal bovine serum-stimulated formation of lipid droplets. Silenced expression of cPLA2 inhibits the formation of lipid droplets. Inhibition of cPLA2alpha under lipid droplets forming conditions alters endoplasmic reticulum structure
progressive inactivation of Lp-PLA2 during low density lipoprotein oxidation leads to an increased uptake of oxidized low density lipoprotein by macrophages, which can be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxidized low density lipoprotein. Inhibition of Lp-PLA2 activity has no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from moderately oxidized low density lipoprotein, moderately oxidized low density lipoprotein with inhibited LpPLA2 activity, heavily oxidized low density lipoprotein and heavily oxidized low density lipoprotein with inhibited LpPLA2 activity
knockdown of the enzyme in hepatitis C virus-infected cells or hepatitis C virus replicon-containing cells by small interfering RNA significantly suppresses hepatitis C virus replication and assembly, not the viral entry, overview. In addition, the chemical inhibitor methyl arachidonyl fluorophosphonate, which specifically inhibits phospholipase A2, reduces hepatitis C virus replication and assembly. The membranous web structure formation is defective
compared with the wild type, the plpA mutant exhibis reduced mortality, systemic infection, and inflammation in mice as well as low cytotoxicity toward the human epithelial INT-407 cells
lack of cPLA2alpha prolongs the G1 phase and reduces the proliferating capacity in response to mitogen stimulation without a significant change in the duration of the other phases of the cell cycle
mice deficient in secreted phospholipase A2 IIF are protected from epidermal hyperplasia in psoriasis, contact dermatitis, and skin cancer, where ethanolamine lysoplasmalogen is selectively reduced in the KO skin relative to wild-type skin
primary microglial cells isolated from cPLA2alpha-deficient mice generate significantly less nitric oxide and reactive oxygen species as compared with the wild-type mice. Microglia isolated from iPLA2beta-deficient mice do not show a decrease in LPS-induced nitric oxide and reactive oxygen species production
when fed a high-fat diet, sPLA2-IIE-deficient mice display lower weight gain, adiposity, and fatty liver, accompanied by alterations in plasma lipoprotein profiles
compared with the wild type, the plpA mutant exhibis reduced mortality, systemic infection, and inflammation in mice as well as low cytotoxicity toward the human epithelial INT-407 cells
hydrolyzes dipalmitoylphosphatidylcholine monolayers in the presence of a supersaturated calcium oxalate subphase, inducing the rapid and plentiful nucleation of calcium oxalate at the lipid interface. Calcium oxalate crystal growth at a ternary monolayer of dipalmitoylphosphatidylcholine, palmitic acid, and a 22-carbon chain lysophospholipid dramatically increases relative to monolayers of just dipalmitoylphosphatidylcholine
a key role for JNK-mediated cPLA2alpha phosphorylation at Ser505 in the sequence of events leading to translocation and activation of the enzyme to phagosomal membranes in human macrophages
acidic PLA2-II, in contrast to the basic Asp49 counterparts present in the same venom, lacks myotoxic, cytotoxic, and anticoagulant activities. It does not show hypotensive and anti-platelet aggregation activities and is not lethal to mice at intravenous doses up to 100 microg (5.9 microg/g), indicating its lack of neurotoxic activity. It shows a moderate induction of local edema in vivo. Acidic PLA2-II does not play a key role in the pathophysiology of envenomings, its purpose may be restricted to digestive functions. Acidic and basic PLA2s form two different antigenic groups in venom
activation of gIVaPLA2 is an essential step in polymophonuclear leukocyte migration in vitro. Change in polymorphonuclear leukocyte cell shape and migration correspond to increased activity of cytosolic gIVaPLA2 and translocation of gIVaPLA2 to the nuclear membrane. F-actin polymerization, another essential step for cell migration, is not regulated by gIVaPLA2
adsorption of PLA2 to model membranes is not primarily driven by electrostatic interactions. Subsequent lipid desorption, which is linked to the bilayer-disrupting activity of PLA2, is significantly affected by membrane electrostatics. Specifically, a nonhydrolytic bilayer-disrupting activity of PLA2 targets anionic membranes, triggering a change in bilayer topology
cPLA2 alpha plays an important role in the pathogenesis of collagen-induced arthritis. cPLA2 alpha activity increases in hind paws of collagen-induced arthritic mice
cPLA2 may be a potential source of fatty acid hydroperoxides. cPLA2 is a key mediator of the high state 1 Amplex Red signal (thought to be highly specific for hydrogen peroxide) that occurs in response to denervation, most likely by preventing the release of fatty acid hydroperoxides from lipid hydroperoxides in the bilayer. Elevation of cPLA2 is potentially a common phenomenon in mice that exhibit muscle atrophy associated with a loss of innervation
cPLA2-alpha is the major enzyme responsible for lipid mediator production in human macrophages. cPLA2-alpha is a critical enzyme for the release of arachidonic acid which is then available for conversion to eicosanoids
cPLA2alpha contribution to lipid droplets biogenesis. Overexpression of cPLA2alpha enhances occurrence of lipid droplets. Role in lipid droplets biogenesis is not because of the generation of arachidonic acid, nor is it related to neutral lipid synthesis. cPLA2 is not involved in the synthesis of neutral lipids during lipid droplets biogenesis. cPLA2alpha is not involved in the channeling of extracellular fatty acids into neutral lipids
GIIA PLA2 is a potent antimicrobial agent. Role of the GVIA PLA2 in different signaling pathways. GVIIA PLA2 has anti-inflammatory activity in vivo, is a positive risk factor in coronary heart disease
group III sPLA2 may play an important role in the initiation and development of hepatic fibrosis. Expression of collagen III is upregulated in LX-2 cells after incubation with the recombinant protein. Group III sPLA2 can bind to specific sites (specific receptor), not lipids, on LX-2 cells membrane. Group III sPLA2 is a component of excretory-secretory products
GVIA PLA2 plays an important role in bone formation, apoptosis, insulin secretion, and sperm development. GVIA PLA2 in combination with the GIVA PLA2 play an important role in Wallerian degeneration and axon regeneration in nerve injury. GIVA PLA2 is generally considered to be a central enzyme mediating generation of eicosanoids and hence many inflammatory processes
induces apoptotic death of human leukemia K562 cells in a concentration- and time-dependent manner. Degradation of procaspases, production of tBid, loss of mitochondrial membrane potential, Bcl-2 degradation, mitochondrial translocation of Bax, and cytochrome c release in PLA2-treated cells. PLA2 treatment increases Fas and FasL protein expression and activates p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun NH2-terminal kinase) in K562 cells. SB202190 pretreatment promotes the cytotoxic effect of PLA2 toward K562 cells in a time-dependent manner. SP600125 (JNK inhibitor) abolishes the cytotoxic effect of PLA2 and PLA2-induced autocrine Fas death pathway
interaction between hemocytes of bloodsucking bug and Saccharomyces cerevisiae cells is mediated by a rapid generation of arachidonic acid and its products through the action of PLA2
iPLA2 is responsible for the enhanced Mn2+ entry occurring upon Ca2+ store depletion, iPLA2 hydrolysis products are involved in the gating of store-operated channels
is a mixed-type inhibitor of thrombin and effectively inhibits thrombin-induced platelet aggregation. Does not require a plasma cofactor, the inhibition is direct. Strongly prolongs the thrombin clotting time (25fold at 0.0000475 mM) with whole human blood plasma. Possesses relatively weak enzymatic activity and is nontoxic to PC12 cells at concentrations up to 0.015 mM, but evokes neurite outgrowth in these cells at a concentration of approximately 0.001 mM, does not impair the adhesion of PC12 cells to plates. At concentrations up to approximately 0.00005 mM, at which the thrombin-clotting time is substantially prolonged, the enzyme exerts no detectable effects on both the intrinsic and extrinsic pathways of the coagulation cascade, thus is a selective thrombin inhibitor. Is at least 2 orders of magnitude less cytotoxic than PLA2 CM2 from Naja kaouthia
late stage of Golgi assembly occurs via membrane tubules, whose formation is dependent on PLA2 activity and dynein-dependent microtubule transport to complete the process
Lp-PLA2 activity reduces the uptake of oxidized low density lipoprotein by peritoneal macrophages. Lp-PLA2 does not affect the uptake of oxidized low density lipoprotein via the ApoB moiety. Lp-PLA2 reduces the uptake of oxidized low density lipoprotein via the lipid moiety
nPLA reduces infarct volume in rats subjected to focal transient cerebral ischemia and alleviates the neuronal damage in organotypic hippocampal slices subjected to oxygen-glucose deprivation. Staurosporine or oxygen-glucose deprivation mediated apoptotic cell death in astrocytoma cells is reduced by nPLA with a corresponding reduction in caspase 3 activity. Protective effects of nPLA at sub-lethal concentrations of the protein
PLA2 induces caspase-dependent death in human SK-N-SH cells. PLA2 treatment induces Fas and FasL protein expression, leads to activation of p38 MAPK, inactivation of ERK, reactive oxygen species generation and elevation in intracellular Ca2+ concentration. PLA2-induced cell death is, in part, elicited by upregulation of Fas and FasL, which is regulated by Ca2+- and reactive oxygen species-evoked p38 MAPK activation, and suggests that non-catalytic PLA2 plays a role for the signaling pathway
PLA2 inhibits efficiently tumor cells adhesion and migration. PLA2 is not cytotoxic up to 0.002 mM during 4 days on human cell lines IGR39 (melanoma) and HT1080 (fibrosarcoma). Completely abolishes cell adhesion of IGR39 cells to fibrinogen and fibronectin in a dose-dependent manner, while attachment to laminin-1 and vitronectin is only slightly affected. The enzyme has no effect on type I collagen, integrin-independent substratum and poly-L-lysine. PLA2 abolishes HT1080 cells migration towards fibronectin and fibrinogen in a dose-dependent manner. Anti-tumor effect of PLA2 is mediated by alpha5beta1 and alphav-containing integrins
promutoxin can provoke microvascular leakage in the skin of rats and induce a dose-dependent release of histamine from colon, lung and tonsil from human mast cells in vitro
role of iPLA2 in enhanced superoxide generation in neutrophils from people with diabetes mellitus, iPLA2 presents an alternate pathway independent of protein kinase C and phosphatidic acid phosphohydrolase-1 hydrolase signaling. The iPLA2 does not regulate cell apoptosis or cell death in neutrophils, iPLA2 regulates superoxide generation independently of p47phox or pleckstrin phosphorylation. The iPLA2-derived arachidonic acid activates NAPDH oxidase to generate superoxide anion
sPLA2 activity is present in lumbar cerebrospinal fluid from healthy individuals 20-77 years old that does not depend on either sex or age. Cerebrospinal fluid sPLA2 activity is increased in patients with Alzheimer disease
sPLA2 influences the proliferation and/or survival of limb mesenchymal cells. Treatment of wing bud mesenchymal cells with exogenous sPLA2 promotes cell death by activating MMP-9 (matrix metalloproteinase-9) through receptor-mediated signalling and increasing type I collagen degradation. Chondro-inhibitory actions by sPLA2 are prevented by functional blocking of FcRY (chicken yolk sac IgY receptor) and by inhibition of ERK (extracellular-signal-regulated kinase) activity
sPLA2s (sPLA2-IIA) and Lp-PLA2 are associated with atherogenesis and its complications. Increased levels of these two phospholipases are related with an increase in complex coronary lesions and increase in major cardiovascular clinical events, respectively. sPLA2 may play an important role in atherogenesis by modifying low density lipoprotein particles in the arterial wall, thereby enhancing their aggregation, retention, and macrophage uptake. Cytotoxic compounds from Lp-PLA2 play an important in plaque vulnerability, Lp-PLA2 has a predominantly proinflammatory role in atherogenesis
ex vivo, whole venom and TX-I phospholipases A2 cause blockade of the neuromuscular transmission in young chick biventer cervicis preparations similar to other isolated snake venom toxins from the Bothrops genus. In vivo, both induce local myotoxicity and systemic interleukin-6 response upon intramuscular injection, additionally, induce moderate footpad edema. In vitro, both induce low cytotoxicity in skeletal muscle myoblasts, however TX-I phospholipases A2 is able to lyse myotubes
group X secreted phospholipase A2 (sPLA2) acts as a potent inhibitor of sperm motility that decreases track speed and lateral displacement of the head of both noncapacitated and capacitated sperm. sPLA2 selects a sperm subpopulation for fertilization based on its effect on sperm motility
phospholipase A2 enzymes have an important role in the earliest steps of membrane tubule formation at the trans-Golgi network, which are utilized for membrane trafficking
the enzyme does not show myotoxic activity, but induces edema and actively participates in the pathogenesis of snake bite. The enzyme is able to induce increments in interleukin-12p40, TNF-alpha, interleukin-1beta and interleukin-6 levels and no variation of interleukin-8 and interleukin-10 in human peripheral blood mononuclear cells stimulated in vitro, suggesting that the enzyme induces proinflammatory cytokine production by human mononuclear cells
the enzyme inhibits the blood coagulation cascade non-enzymatically by binding with coagulation factor Xa, even in the absence of phospholipids and Ca2+ and thus slows down the blood coagulation by partially inhibiting the prothrombin activation
the functions of 1-CysPrx/aiPLA2 include the protection of cell membrane phospholipids against oxidative damage (peroxidation) and the metabolism (hydrolysis) of phospholipids, such as those of lung surfactant
the phospholipase A2 toxin I displays a heparin binding C-terminal region, which is probably responsible for the cytotoxic and bactericidal effects. Toxin I is able to induce cytotoxicity on THP-1 cells in vitro as well as lethality in BALB/c mice. Toxin II also induces mild myotoxic effects on mouse skin, but is devoid of hemolytic effects on human erythrocytes up to 0.5 mg/ml
enzyme presents bactericidal and Ca2+-independent liposome membrane-damaging activities. Phospholipid bilayer permeabilization by the enzyme is independent of catalytic activity
enzyme shows strong anticoagulant effect via thrombin inhibition with a Ki value of 380 nM as well as by binding to pro-coagulant phospholipids of plasma. In ex-vivo conditionsthe enzyme at 1.0 microM is non-hemolytic and non-cytotoxic to mammalian cells. It does not inhibit the collagen-induced aggregation of platelets. At a dose of 5 mg/kg, the enzyme is not lethal to mice after 48 h of injection
isoform PLA2IValpha is selectively activated upon Fc receptor-mediated phagocytosis in macrophages and rapidly translocates to the site of the nascent phagosome. Pharmacological inhibition of PLA2IValpha by pyrrophenone reduces particle internalization by up to 50%. Fibroblasts from PLA2IValpha knock-out mice overexpressing FcRIIA and able to internalize IgG-opsonized beads show 50% lower phagocytosis, compared with wild-type cells. Transfection of the catalytically inactive deleted PLA2IValpha mutant PLA2IValpha(1-525) and point mutant PLA2IValpha-S228C promotes recovery of this impaired function. Transfection of the PLA2IValpha C2 domain, but not of PLA2IValpha-D43N, which cannot bind to membranes, rescues FcR-mediated phagocytosis
phospholipase A2 activity plays key roles in generating lipid second messengers and regulates membrane topology through the generation of asymmetric lysophospholipids. The Group VIA phospholipase A2 (GVIA-iPLA2) subfamily of enzymes is implicated in numerous cellular processes, including proliferation, apoptosis, and membrane transport steps. Role for acidic phospholipids in regulating GVIA-iPLA2 function. Membrane composition and the presence of nucleotides play key roles in recruiting and modulating the isozyme activity in cells
the cytosolic phospholipase A2 gamma contributes to membranous web formation, hepatitis C virus replication, and assembly. The PLA2G4C gene is identified as a host gene with upregulated expression upon hepatitis C virus infection. The enzyme colocalizes with the hepatitis C virus proteins NS4B and NS5A in cells infected with JFH-1 and interacts with NS4B. In addition, the enzyme is able to transport the hepatitis C virus nonstructural proteins from replication sites to lipid droplets, the site for hepatitis C virus assembly
phosphatidylinositol is a substrate of cPLA2alpha in the human platelet and the majority of phosphatidylinositol lost during thrombin stimulation is a result of cPLA2alpha activity
phospholipases A2 (PLA2s) play key roles in the pathogenesis of the local tissue damage characteristic of crotaline and viperine snake envenomations. ColTx-I induces a complex series of degenerative events associated with edema, inflammatory infiltrate and skeletal muscle necrosis. IT plays a relevant role in Crotalus oreganus lutosus envenomation
role in adaptive immunity. secreted phospholipase A2-IID preferentially hydrolyzes arachidonic acid- or docosahexaenoic acid-containing phosphatidylethanolamine in lymph nodes, thereby mobilizing arachidonic acid- and particularly docosahexaenoic acid-derived antiinflammatory lipid mediators that attenuate the Th1-mediated immunity
secreted phospholipase A2 IIF referentially hydrolyzes plasmalogen secreted from keratinocytes to produce lysoplasmalogen, which in turn promotes the hyperproliferation and activation of keratinocytes, leading to aggravation of epidermal-hyperplasic disorders. sPLA2-IIF transgenic mice spontaneously developed psoriasis-like epidermal hyperplasia and alopecia, with preferential hydrolysis of DHA-containing phosphatidylethanolamine to give rise to acyl and plasmalogen (P-) forms of lysophosphatidylethanolamine molecular species in addition to (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoate (DHA)
the crude venom of Daboia r. russelii has prominent cytotoxic effect on HEK-293 and MCF-7 cells in a dose dependent manner. Phospholipase A2 enzyme from Indian viper (Daboia russelii russelii) venom targets both factor X and factor Xa for its anticoagulant activity
the enzyme has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2
the enzyme has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2
the enzyme has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2
the enzyme has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2
the enzyme has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2. The enzyme has been implicated in acute lung injury, carcinogenesis, neurodegenerative diseases, diabetes and male infertility
the enzyme plays a role as an omega3 PUFA mobilizer. sPLA2-X secreted from sperm acrosomes selectively hydrolyzes docosahexaenoic acid- or docosapentaenoic acid-containing phosphatidylcholine in the sperm membrane to release docosahexaenoic acid, docosapentaenoic acid, and lysophosphatidylcholine, and the defective fertilization ability of sPLA2-X KO sperm was corrected by these lipids (docosapentaenoic acid in particular), suggesting the importance of the sPLA2-X-driven docosapentaenoic acid for successful fertilization
the enzyme displayed an anticoagulant action, inhibition of platelet aggregation induced by epinephrine (about 80%) and ADP (24%). The enzyme induces myonecrosis and the release of cytokines (IL-10, IL-12 and TNF-alpha) in macrophages culture