The role of sphingolipids in arachidonic acid metabolism

The arachidonic acid (aa) cascade is regulated mainly by the actions of two rate-limiting enzymes,phospholipase a2 (pla2) and inducible cyclooxygenase-2 (cox-2). pla2 acts to generate aa,which serves as the precursor substrate for cox-2 in the metabolic pathway leading to prostaglandin production. amongst more than 30 members of the pla2 family,cytosolic pla2α (cpla2α,group iva) plays a major role in releasing aa from cellular membranes. sphingolipids are a novel class of bioactive lipids that play key roles in the regulation of several cellular processes including growth,differentiation,inflammatory responses,and apoptosis. recent studies implicated a regulatory function of sphingolipids in prostaglandin production. whereas ceramide-1-phosphate and lactosylceramide activate cpla2α directly,sphingosine-1-phosphate induces cox-2 expression. sphingomyelin has been shown to inhibit the activity of cpla 2α. in addition,several sphingolipid analogs including a therapeutic agent currently used clinically are also reported to be inhibitors of cpla2α. this review explores the role of sphingolipids in the regulation of cpla2α and cox-2. © the japanese pharmacological society.