EFFECT OF LYSOPHOSPHATIDYLCHOLINE ON TRANSMEMBRANE SIGNAL-TRANSDUCTION

Lysophosphatidylcholine (LPC), 1-acyl-sn-glycero-3-phosphocholine, is well known as an intermediate of metabolism of phosphatidylcholine (PC ), the main phospholipid component in all eukaryotic and many prokaryo tic cells. LPC is produced as a result of PC hydrolysis by several iso forms of phospholipase A(2) (PLA(2)) and in the reaction mediated by l ecithin-cholesterol acyltransferase that transfers the fatty acid resi due from PC to cholesterol. LPC is classified as a second messengers t hat is produced by activation of cytosolic hormone-activated PLA(2). I t was shown that LPC inhibits transmembrane signaling via receptors, w hich in their active form are linked to G-proteins. There is a viewpoi nt that LPC abolishes formation of the complex between the receptor an d G-protein. The effect of LPC on protein kinase C (PKC) activation is considered in this review. It was shown that low (less than 20 mu M) and high (more than 30 mu M) concentrations of LPC activated and inhib ited PKC, respectively. The mechanism of LPC-induced activation of PKC still remains unclear. However, the studies of the effect of LPC on s ignal transduction through the PKC-mediated pathway showed that LPC pr obably plays an auxiliary role. It was suggested that LPC may prolong the effect of the direct activators of PKC (such as 1,2-diacylglycerol or phorbol esters). The physiological role of the elevation of LPC le vel in tissues is associated with its ability to enhance or even evoke cell proliferation, stimulate adhesion and differentiation of lymphoi d cells, have mitogenic effect on macrophages, activate human T-lympho cytes, initiate monocyte chemotaxis, decrease myocardial sensitivity t o cholinergic stimulation, impair contractility of arterial smooth mus cle, and modulate aggregation of platelets.