Disease relevance of PLA2G2A

• Beyond its potential diagnostic and prognostic significance, this result suggests the intriguing possibility that the activity of PLA2G2A may suppress progression or metastasis of human gastric cancer [1].
• Additional genes involved in osteoclastogenesis and bone resorption, which were statistically different, include annexin 2, SMAD, PLA2G2A, and TGFbeta1 [2].
• To test the hypothesis of a correlation between PLA2G2A gene alterations and human tumor development, we screened 14 patients with FAP and 20 patients with sporadic colorectal cancer for germline and somatic PLA2G2A gene mutations [3].
• Invading bacteria such as Staphylococcus aureus induce mobilization of professional phagocytes (e.g., neutrophils) and extracellular antibacterial proteins (e.g., group IIA phospholipase A2 (gIIA PLA2)) [4].
• Incubation with pertussis toxin prior to the addition of either sPLA2 or LPA only showed abrogation of the response to LPA, thus suggesting the involvement of pertussis-sensitive Gi-proteins in the case of LPA [5].

Psychiatry related information on PLA2G2A

• In addition, because many neurodegenerative diseases are associated with increased oxidative and inflammatory responses, an attempt was made to include studies on PLA2 in cerebral ischemia, Alzheimer's disease, and neuronal injury due to excitotoxic agents [6].
• A hereditary factor predisposing patients to affective disorders may be a gene defect at either PLA2 or in its regulation [7].
• The mechanisms of action of tricyclic antidepressants, lithium, electroconvulsive shock, and some novel antimanic agents can be described in terms of alterations of PLA2 activity [7].
• In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse [8].
• For PLA2, the rate of enzymatic activity was inversely correlated (p < 0.001) with the duration of the latency period of the enzymatic reaction [9].

High impact information on PLA2G2A

• SPH hydrolysis, which is provoked by various cytokines, regulates sPLA2 activity, and the novel lipid mediator LPA can be generated by this pathway [10].
• We conclude that PLA2/5-lipoxygenase-mediated leukotriene C4 production constitutes a novel and specific signal transduction pathway in growth factor action [11].
• We report the cloning and expression of a cDNA encoding a high molecular weight (85.2 kd) cytosolic phospholipase A2 (cPLA2) that has no detectable sequence homology with the secreted forms of PLA2 [12].
• Phospholipase A2 (PLA2) enzymes are critical regulators of prostaglandin and leukotriene synthesis and can directly modify the composition of cellular membranes [13].
• Here we report the refined, three-dimensional crystal structure at 2.2 A resolution of recombinant human rheumatoid arthritic synovial fluid PLA2 [14].

Chemical compound and disease context of PLA2G2A

• BACKGROUND: Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel diseases (IBD) involving synthesis of eicosanoids from arachidonic acid (AA), which is released from membrane phospholipids by phospholipase A2 (PLA2) [15].
• CONCLUSIONS: As PLAP values were increased in the intestinal mucosa of IBD patients and mice with colitis, as well as in LPS treated cultured HT-29 cells, a role was postulated for PLAP in increasing PLA2 activity, which leads to the increased synthesis of eicosanoids in intestinal tissues of patients with these inflammatory diseases [15].
• The levels of adenosine found in sputum from patients with cystic fibrosis with moderate to severe lung disease stimulated apical prostaglandin release in Calu-3 and CFBE41o- cells, implicating adenosine regulation of phospholipase A2 (PLA2) activity [16].
• However, regarding the comparatively low activity of PLA2 in gallbladder bile PLA2 seems to be of only minor pathophysiological importance in the formation of cholesterol gallstones [17].
• The sPLA2-induced [Ca2+]c peak was sensitive to Bordetella pertussis toxin and inhibited by caffeine, suggesting its mediation by inositol 1,4,5-trisphosphate (IP3). sPLA2 induced tyrosine phosphorylation and membrane targeting of phospholipase Cgamma-1 (PLCgamma-1) [18].

Biological context of PLA2G2A

• Expression of PLA2G2A, a gene previously implicated as a modifier of the Apc(Min/+) (multiple intestinal neoplasia 1) mutant phenotype in the mouse, was significantly correlated with patient survival [1].
• The Group IIA phospholipase gene (PLA2G2A) protein coding regions exhibit significant homology with recently described Group IIC (PLA2G2C) and Group V (PLA2GV) genes [19].
• Accumulation of gIIA PLA2 in inflammatory fluids confers potent extracellular antistaphylococcal activity and at lower concentrations promotes bacterial phospholipid degradation during phagocytosis of S. aureus by human neutrophils [4].
• D-alanylation of (lipo) teichoic acids of S. aureus increases bacterial resistance to gIIA PLA2 approximately 100-fold, raising the possibility that the resistance of ingested S. aureus to related gV and gX secretory PLA2 present in human neutrophil granules depends on D-alanylation mediated by the dlt operon [4].
• Phospholipase A2 (PLA2) proteins affect cellular activation, signal transduction, and possibly innate immunity [20].

Anatomical context of PLA2G2A

• The extreme potency of the gIIA PLA2 toward dltA S. aureus suggests that even small amounts of this extracellular enzyme mobilized early in inflammation could contribute substantially to the overall cytotoxicity of acute inflammatory exudates toward S. aureus when D-alanylation of (lipo)teichoic acids is limiting [4].
• Synergistic effect of interleukin-1 beta and tumor necrosis factor alpha on PGE2 production by articular chondrocytes does not involve PLA2 stimulation [21].
• There was no cross-reactivity with other (secretory) isoforms of PLA2 (sPLA2 types I-III) either from porcine pancreas, human synovial fluid, or bee venom [22].
• Phospholipase A2 (PLA2) activities in rheumatoid synovial fibroblasts (RSF) stimulated with interleukin-1 beta (IL-1 beta) were investigated [23].
• IL-1 beta treatment did not increase the level of secretory PLA2 (sPLA2) activity or sPLA2 protein in the conditioned medium or subcellular fractions of lysed RSF [23].

Associations of PLA2G2A with chemical compounds

• The purpose of this study was to define the role of secretory phospholipase A2 (sPLA2), calcium-independent PLA2, and cytosolic PLA2 (cPLA2) in arachidonic acid (AA) release from fMLP-stimulated human neutrophils [24].
• Treatments with inhibitors of the catalytic effect of sPLA2 such as p-bromophenacyl bromide and dithiothreitol did not prevent the effect on cPLA2 activation [5].
• In contrast, preincubation of 1321N1 cells with the antagonist of the sPLA2 receptor p-aminophenyl-alpha-D-mannopyranoside-bovine serum albumin, blocked cPLA2 activation with a EC50 similar to that described for the inhibition of binding of sPLA2 to its receptor [5].
• In contrast, IL-1-induced sPLA2 gene expression determined in the same cell samples was weak and most often rapid, and dexamethasone further stimulated it [25].
• (2) cPLA2 is active at nM calcium (Ca2+) concentrations; sPLA2 requires microM Ca2+ levels [26].

Physical interactions of PLA2G2A

• Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2 [27].
• In addition, sPLA2 potentiated the binding of C-reactive protein (CRP) to these cells [28].

Regulatory relationships of PLA2G2A

• In an attempt to investigate early molecular events in CD69-mediated cell activation we studied the relative contribution of phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase C-dependent pathways during platelet activation induced by CD69 stimulation [29].
• Moreover, maximum sPLA2 levels induced by IL-2 were higher in patients who had progressive disease after therapy than in patients who had stable disease or a partial response [30].
• TNF-induced NF-kappaB activation was also strongly reduced in cells stimulated in the presence of the secretory PLA2 (sPLA2) inhibitors 12-epi-scalaradial and LY311727 [31].
• As sPLA2 requires Ca2+ for activity, these results indicate that both Ca2+ mobilization and cPLA2 activation induced by sPLA2 are unrelated to phospholipase activity but dependent on signaling mechanisms [18].
• The non-proteinaceous polycationic hexadimethrine and acidic protein casein failed to inhibit platelet sPLA2 activity [32].

Other interactions of PLA2G2A

• RESULTS: Expression of PLA2G2A and PLA2G5, the main placenta phospholipases, was greater (P < 0.05) in placenta of obese compared with control neonates and was associated with increased 20:3 and 20:5 omega-3 polyunsaturated fatty acids [33].
• The genes PLA2G2A (1p35.1-36) and TP73 (1p36.3) were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss [34].
• Moreover, treatment of 1321N1 cells with the MAP kinase kinase inhibitor PD-98059 inhibited the activation of both cPLA2 and p42 MAP kinase produced by sPLA2 [5].
• In contrast, 14 kDa, secreted PLA2 (sPLA2), which was also produced by RSF, was not affected by IL-1 beta treatment [35].
• HVSMC contained mRNA encoding both the secreted and cytosolic forms of phospholipase A2 (sPLA2 and cPLA2, respectively) [36].

Analytical, diagnostic and therapeutic context of PLA2G2A

• The mRNA levels of cPLA2, sPLA2, and COX-2 were also measured by Northern blotting, using specific complementary DNA probes [21].
• Synovial fluid from arthritic patients contains multiple forms of phospholipase A2 (PLA2), as resolved by high performance liquid chromatography (Seilhamer, J.J., Plant, S., Pruzanski, W., Schilling, J., Stefanski, E., Vadas, P., and Johnson, L. K. (1989) J. Biochem. (Tokyo), submitted for publication) [37].
• To date, there are very limited data on PLA2 protein by Western blotting after cerebral ischemia, though some immunohistochemical studies (for cPLA2 and sPLA2) have been reported [38].
• Bone marrow transplantation to LDL receptor-deficient mice was performed to study sPLA2 IIa in atherosclerosis [39].
• Cacospongionolide B, that is bioavailable when is given orally, reduced the elevated levels of sPLA2 present in paw homogenates of rats with adjuvant arthritis [40].

References