Modulation of lipid derived mediators by polyunsaturated fatty acids

Cell stimulation by a number of agonists triggers the formation of products of lipid hydrolysis, which act either as intracellular mediators of signal transduction or as modulators of cell-cell interactions. This process is mediated by the activation of hydrolytic enzymes, the phospholipases (PLase), especially the A2 and C, acting on cell phospholipids (PL). Among the major products being formed, the following: a) the inositol phosphates (IP), especially IP3, and diacylglycerols (DAG) generated intracellularly from phosphoinositides through PLase C, b) the eicosanoids, the arachidonic acid (AA) metabolites produced through combined PLase A2 and (cyclo- and lip-) oxygenase activities, and released from cells, c) the ether lipid PAF, derived from alkylacyl phosphatidylcholine through PLase A2, have attracted the attention of investigators for their important biological roles. Interest has also been recently developed towards products of sphingolipid hydrolysis, sphingosine and ceramide, which are generated by various cell types after stimulation, and exert biological activities. Cell glycerophospholipids are rich in long-chain polyunsaturated fatty acids (PUFA) of the n-6, namely AA 20:4 n-6, and n-3, mainly docosahexaenoic acid (DHA) 22:6, series. These compounds are differentially distributed among the various PL classes and their levels in cells are modulated through the intake with the diet of either the 18-C fatty acids (FA), precursors, linoleic 18:2 n-6, and, alpha-linolenic 18:3 n-3, respectively--followed by conversion to their long-chain PUFA derivatives, or through the intake of the performed compounds.(ABSTRACT TRUNCATED AT 250 WORDS)