Functional Association of Type IIA Secretory Phospholipase A2 with the Glycosylphosphatidylinositol-anchored Heparan Sulfate Proteoglycan in the Cyclooxygenase-2-mediated Delayed Prostanoid-biosynthetic Pathway

Characterization of Secretory Type IIA Phospholipase A2 (sPLA2-IIA) as a Glycyrrhizin (GL)-Binding Protein and the GL-Induced Inhibition of the CK-II-Mediated Stimulation of sPLA2-IIA Activity in Vitro.

“…This correlation will be elucidated by the in vivo experiments for direct detection of the specific phosphorylation of cellular sPLA 2 -IIA with membrane-associated CK-II 17) in interleukin-1 (IL-1)/tumor necrosis factor (TNF)-stimulated cells. This possibility is strongly supported by the following recent reports: (i) sPLA 2 -IIA is the most widely distributed isozyme in humans and rats, 20) and is extremely induced by proinflammatory stimuli, such as bacterial endotoxin, IL-1 and TNF 21) ; (ii) this isozyme is localized in the punctate and perinuclear domains in IL-1/TNF-stimulated cells and is accumulated in the caveolae of cytokine-stimulated cells; 22,23) and (iii) caveolae are highly enriched in caveolins (structural proteins), b 2 -adrenergic receptor, cAMP-dependent protein kinase (A-kinase) 24) and receptor tyrosine kinases, such as platelet-derived growth factor receptor 25) and ErbB receptor, 26) corresponding signal transduction for metabolic and mitogenic effects, and functions as a lipid scaffold for organizing the molecular interactions of multiple signaling pathways. 27) For understanding clearly the biochemical mechanism involved in the GL-induced anti-inflammatory effect in vivo, further analytical studies will be required (i) to confirm a GL-sensitive sPLA 2 among at least five isozymes (sPLA 2 -IIA, sPLA 2 -IIC, sPLA 2 -IID, sPLA 2 -IIE and sPLA 2 -IIF) 28,29) of the sPLA 2 -II family in various clinical materials, such as synovial fluid of patients with rheumatoid arthritis and sera of patients with autoimmune diseases; (ii) to characterize the regulatory mechanism of the GL-sensitive sPLA 2 by membrane-associated CK-II or other protein kinases [A-kinase, Ca 2ϩ /phospholipid-dependent protein kinase (C-kinase), mitogen-activated protein kinase (MAP-kinase) and receptor tyrosine kinases] in vivo and in vitro; and (iii) to determine the suppressive effects of GL, GA and oGA on the induction of a GL-sensitive sPLA 2 in the cytokine-mediated response at the cellular level.…”

The role of phospholipases A2 in schizophrenia

“…14 PLA2G4A initiates AA release and eicosanoid production, whereas PLA2G2A enhances the production of AA (Figure 2). [15][16][17][18] Mice with the genes for PLA2G4A and PLA2G2A nullified (knocked out) do not produce eicosanoids, have reduced incorporation rates of free AA into cell membranes, yet normal AA levels. 19,20 PLA2G6A cleavage of phospholipids is primarily for the purpose of cellular membrane remodelling, by altering phospholipids/fatty acid ratios and modifying membrane fluidity.…”

“…5,11,17,28 The colocalisation of monoaminergic receptors with PLA2G4A, PLA2G2A and eicosanoid-synthesising enzymes further emphasise their importance for monoaminergic neurotransmission. 15,[29][30][31] The proper functioning and availability of these PLA2s are therefore crucial for G-proteincoupled neurotransmission.…”

Localization of Group V Phospholipase A2 in Caveolin-enriched Granules in Activated P388D1 Macrophage-like Cells

“…To test this possibility, cellular treatment with LPS was conducted in the presence of heparin in the extracellular medium. Heparin, a cell-impermeable polysaccharide, tightly binds Group V sPLA 2 in the incubation medium, thereby preventing the enzyme from interacting with the plasma membrane (8,20). As a result of this action, heparin strongly blunts agonist-induced delayed AA mobilization in macrophages as well as other cells (20 -22).…”