Disease relevance of PLA2G1B

• A specific secretory PLA2, sPLA2-X, is shown here to neutralize human immunodeficiency virus type 1 (HIV-1) through degradation of the viral membrane [1].
• Constitutive and LPA-induced LPA synthesis by ovarian cancer cells is differentially regulated with respect to the requirement of specific phospholipase A2 (PLA2) subgroups [2].
• Enhanced secretory group II PLA2 activity in the tears of chronic blepharitis patients [3].
• INTRODUCTION: There is circumstantial and contradictory evidence of the role of group IIA phospholipase A2 (PLA2) in acute pancreatitis [4].
• Inhibition of PLA2 similarly abolished the cold responses of the majority of cold-sensitive dorsal root ganglion neurons [5].

Psychiatry related information on PLA2G1B

• We have found evidence of an allelic association between bipolar disorder and a marker at the pancreatic phospholipase A2 gene (PLA2A) in this region (p < or = 0.01) [6].
• 1. The maximum evidence for linkage was given by a polymorphism at the gene encoding secretory phospholipase A2 (PLA2A), a candidate gene for affective disorder [7].

High impact information on PLA2G1B

• These results are consistent with the constitutive expression of PLA2 and COX-2 in spinal cord, the spinal release of prostaglandins by persistent afferent input, and the effects of prostaglandins on spinal excitability [8].
• The lacking H+ efflux could be restored (1) by adding lysophosphatidylcholine (LPC), a product of PLA2 activity, to vacuoles in situ and (2) by exposing intact cells to isotonic, near-neutral HEPES buffers [9].
• Under physiological conditions mitochondria can repair peroxidative damage in part through a remodeling mechanism via the deacylation-reacylation cycle mediated by phospholipase A2 (PLA2) and acyl-coenzyme A-dependent monolysocardiolipin acyltransferase [10].
• Related group V and X PLA2, which are present within PMN granules, do not contribute to bacterial phospholipid degradation during and after phagocytosis even when added at concentrations 30-fold higher than that needed for action of the gIIA-PLA2 [11].
• MPIF-1 induces a rapid dose-dependent release of [3H]arachidonic acid from monocytes that is dependent on extracellular calcium and is blocked by phospholipase A2 (PLA2) inhibitors [12].

Biological context of PLA2G1B

• Thus, the MPIF-1 signal transduction pathway appears to include binding to CCR1; transduction by G proteins; effector function by phospholipase C, protein kinase C, calcium flux, and PLA2; and cytoskeletal remodeling [12].
• Phospholipase A2s (PLA2) are a class of enzymes, which catalyze the hydrolysis of membrane phospholipids at the sn-2 position to release fatty acids and lysophospholipids [13].
• The positive correlation of spatial descriptor Pmiz with inhibitory activity shows that proper orientation of the substitution at R position towards Z-axis is necessary to facilitate the possible interactions of the indole core with active site residues of the PLA2 enzyme [13].
• The PLA2 substrate specificity test revealed group II PLA2 activity [3].
• One resulting clone which encoded the entire porcine PLA2 enzyme was then used to screen various human cDNA and gene libraries [14].

Anatomical context of PLA2G1B

• Furthermore, PLA2 activation is shown to be necessary for filamentous actin formation in monocytes [12].
• We used 2 experimental models in order (1) to determine the presence and functionality of cyclooxygenase (COX) and phospholipase A2 (PLA2) enzymes in human osteoclasts and (2) to study their role in cell metabolism [15].
• PURPOSE: Phospholipase A2 (PLA2) hydrolyzes phospholipids, one of the important constituents of human meibomian gland secretions [3].
• These findings demonstrate that a large number of PLA2 types are expressed in the normal human nasal mucosa [16].
• These results suggest that stimulation of three isoforms of PLA2 by thapsigargin liberates free AA that, in turn, induces capacitative calcium influx in human T-cells [17].

Associations of PLA2G1B with chemical compounds

• Treatment of the cells with the PLA2 inhibitor 4-bromophenacyl bromide (BPB) decreased the cytokine-induced mPGES-1 expression accompanied by decreased PGE2 production whereas the addition of arachidonic acid (AA) upregulated mPGES-1 expression and PGE2 production [18].
• The results indicate that the inflammatory-induced mPGES-1 expression is regulated by PLA2 and 15d-PGJ2 but not by PKC, tyrosine kinase or p38 MAP kinase providing new insights into the regulation of mPGES-1 [18].
• The characterization of PLA2 was performed by the head group preference test and the dithiothreitol (DTT) sensitivity test [3].
• Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor [16].
• In addition, pretreatment of ES cells with mepacrine decreased PRL/IGFBP1 expression and inhibited morphological change, whereas pretreatment with propranolol caused no changes, as compared to cAMP-treated cells, which suggests that PA induces decidualization through phospholipase A2 (PLA2G1B) [19].

Regulatory relationships of PLA2G1B

• Taken together, these results suggest that PLD1 regulates 8-Br-cAMP-induced decidualization through PLA2G1B, and that PLD1 upregulation is essential for the decidualization of ES cells [19].

Other interactions of PLA2G1B

• COX and PLA2 enzymatic activity was evaluated at the single-cell level by fluorescence microscopy [15].
• The relative abundance of the different PLA2 transcripts were aiPLA2 > X approximately = IVA > IIA approximately = IIE approximately = IVB approximately = VI > IB approximately = IID approximately = III approximately = IVC approximately = VII approximately = iPLA2-2 [16].
• Expression of selected genes was confirmed by RT-PCR; p-XSC reduced the levels of COX-2, PLA2, NF-kappaB and Cyclin D1 but enhanced the levels of glutathione peroxidase-5 [20].
• Single-point Monks-Kaplan analysis provided evidence of association between central fat mass and SNPs in two genes - PLA2G1B (P = 0.0067) and P2RX4 (P = 0.017) [21].
• Conclusions: Induction of MMP9 by uPA in THP-1 monocytes is via a pathway involving MEK1-ERK1/2-mediated activation of cytosolic PLA2 and eicosanoid generation [22].

Analytical, diagnostic and therapeutic context of PLA2G1B

• The classification of PLA2 type was done using Western blot analysis with anti-human secretory PLA2 antibody [3].
• Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2 types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected in only one individual on one single occasion [16].
• Electrospray ionization mass spectrometry of cellular phospholipids revealed that iPLA2gamma and other intracellular PLA2 enzymes acted on different phospholipid subclasses [23].
• A fluorimetric assay was applied using the PLA2 specific substrate NBDC6-HPC, thin-layer chromatography of reaction products, and digital image scanning for signal detection [24].
• The aim of this study was to test the proinflammatory action of human secreted phospholipase A2 (sPLA2) in an animal model of synovitis-like inflammation and to compare it with a Group 1 (porcine pancreatic) and a Group 2 (Naja mocambique mocambique) PLA2 [25].

References