Type IIA Secretory PLA2-Mediated Delayed PGE2 Biosynthesis is Regulated by the Products of the Cytosolic PLA2
Phospholipase A2s (PLA2s) comprises a growing family of enzymes that hydrolyze membrane glycerophospholipids at the sn-2 position, generating free fatty acids containing arachidonic acid (AA) and lysophospholipids. The released AA is converted to prostaglandins (PGs) and leukotrienes by cyclooxygenases (COXs) and 5lipoxygenases (5-LOX), respectively. Lysophospholipids themselves often act as lipid mediators and are also metabolized to other bioactive lipids, such as platelet-activating factor. To date, more than ten PLA2 1 and two COX2 isozymes have been identified in mammals. Type IIA secretory PLA2 (sPLA2-IIA) is a 14-kDa PLA2 that requires millimolar levels of calcium for its activation and is induced by various stimuli such as proinflammatory cytokines and endotoxin in many cell types3’6. sPLA2-IIA is referred to as the inflammatory-type PLA2, since it is highly expressed in the plasma and synovial fluids of patients with various inflammatory diseases such as rheumatoid arthritis, pancreatitis, Crohn’s disease, and endotoxic shock6 as well as various cancers’. Cytosolic PLA2 (cPLA2: type IV) is an 85 kDa PLA2 that is constitutively expressed in various cells and tissues8’9. This enzyme preferentially hydrolyzes AA from membrane phospholipids and requires micromolar calcium for its activation. Both the phosphorylation and calcium-dependent translocation of cPLA2 to the membranes are essential for its activation10. Current evidence suggests that the existence of two kinetically distinct PG-biosynthetic responses, the immediate and delayed phases, implies the recruitment of different sets of biosynthetic enzymes to this pathway11.
KeywordsArthritis Aspirin Pancreatitis Ketone Prostaglandin
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