Sphingolipids and cell signaling: involvement in apoptosis and atherogenesis.

This review considers various functional aspects of cell sphingolipids (sphingomyelin, ceramides) and lysosphingolipids (sphingosine-1-phosphate (S1P) and sphingosine phosphorylcholine). Good evidence now exists that they are actively involved in numerous cell-signaling processes. The enzymes responsible for formation and interconversion of cell sphingolipids (sphingomyelinases, ceramidase, sphingosine kinase, S1P-lyase) exhibit high sensitivity to various stimulating factors. This determines the content of individual cell sphingolipids and therefore the mode of cell response. Special attention is paid to preferential localization of sphingolipids in the rigid plasma membrane domains (rafts) coupled to many signal proteins. The suggestion is discussed that ceramide signaling may be based on the modification of fine molecular interactions in lipid rafts, resulting in its clusterization inducing the signal transduction. The review also highlights involvement of sphingolipids in cell proliferation, apoptosis, and in processes implicated to atherosclerosis.