Phospholipase A2

Abstract

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins (PGs) and leukotrienes (LTs). The same reaction also produces lysophosholipids, which represent another class of lipid mediators. So far, at least 19 enzymes that possess PLA2 activity have been identified in mammals. The secretory PLA2 (sPLA2) family, in which 10 isozymes have been identified, consists of low-molecular-weight, Ca2+-requiring, secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, host defense, and atherosclerosis. The cytosolic PLA2 (cPLA2) family consists of 3 enzymes, among which cPLA2alpha plays an essential role in the initiation of AA metabolism. Intracellular activation of cPLA2alpha is tightly regulated by Ca2+ and phosphorylation. The Ca2+-independent PLA2 (iPLA2) family contains 2 enzymes and may play a major role in membrane phospholipid remodeling. The platelet-activating factor (PAF) acetylhydrolase (PAF-AH) family represents a unique group of PLA2 that contains 4 enzymes exhibiting unusual substrate specificity toward PAF and/or oxidized phospholipids. In this review, we will overview current understanding of the properties and functions of each enzyme belonging to the sPLA2, cPLA2, and iPLA2 families, which have been implicated in signal transduction.

Cross-talk between Cytosolic Phospholipase A2α (cPLA2α) and Secretory Phospholipase A2 (sPLA2) in Hydrogen Peroxide-induced Arachidonic Acid Release in Murine Mesangial Cells

“…Materials- [5,6,8,9,11,12,4, Generation of Primary Murine Mesangial Cells-Primary murine MC were cultivated from wild type and cPLA 2 ␣ knockout mice. Cell lines were generated from kidneys taken from 3 cPLA 2 ␣ ϩ/ϩ and 3 cPLA 2 ␣ Ϫ/Ϫ littermates.…”

“…Several mammalian intracellular and small molecular weight (13,000 -16,000) secretory PLA 2 s (sPLA 2 ) have been characterized and classified into different groups (1)(2)(3)(4). Non-secretory PLA 2 s include the Ca 2ϩ -sensitive arachidonoyl-selective 85-kDa group IV␣ cytosolic PLA 2 (cPLA 2 ␣) (5, 6), paralogs of this enzyme (7), and several Ca 2ϩ -independent PLA 2 s (iPLA 2 s) (8).…”

“…Non-secretory PLA 2 s include the Ca 2ϩ -sensitive arachidonoyl-selective 85-kDa group IV␣ cytosolic PLA 2 (cPLA 2 ␣) (5, 6), paralogs of this enzyme (7), and several Ca 2ϩ -independent PLA 2 s (iPLA 2 s) (8). A number of mammalian sPLA 2 s have been identified to date (groups IB, IIA, IIC, IID, IIE, IIF, III, V, X, and XII) and they display distinct yet partially overlapping tissue distributions (4,9,10). Whereas cPLA 2 ␣ has a preferential effect on AA-containing membrane phospholipids as compared with those containing other fatty acids, sPLA 2 s do not exhibit acyl chain specificity.…”

Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2

“…The sPLA 2 s form a growing family of enzymes that catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids, leading to the production of free fatty acids and lysophospholipids that serve as precursors for a variety of lipid-derived mediators involved in numerous biological activities (5,6). To date, 10 different sPLA 2 s, referred to as groups IB, IIA, IIC, IID, IIE, IIF, III, V, X, and XII, have been characterized in mammals (7)(8)(9)(10)(11)(12). Of particular interest, levels of sPLA 2 activity in bronchoalveolar lavage fluids (BALF) of patients with ARDS often correlate positively with the severity of the disease (13).…”

The First Potent Inhibitor of Mammalian Group X Secreted Phospholipase A2: Elucidation of Sites for Enhanced Binding

“…Removal of the benzenesulfonyl protecting group and reduction of the ketone was accomplished in one step by refluxing in excess lithium aluminum hydride. Deoxygenation at the 2-position was accomplished using NaBH 4 and trifluoroacetic acid to produce the 2-ethyl indole 9. N1-benzylation and 4-hydroxy deprotection followed by addition of tert-butyl bromoacetate yielded the tert-butyl oxyethanoate 11.…”