Ceramide, a Sphingolipid Second Messenger

A sphingomyelin cycle was discovered in human myelocytic leukemia HL-60 cells which is activated during differentiation induced with lα,25-dihydroxyvitamin D3. In turn, ceramide, the product of sphingomyelin hydrolysis, plays an important role as a lipid messenger in cell functions including proliferation, differentiation and apoptosis. A novel magnesium-independent, neutral, cytosolic sphingomyelinase was identified as a key enzyme up-stream of ceramide-related signal transduction. The use of cell-permeable ceramides has identified protein phosphorylation and dephosphorylation and nuclear transcription factors as down-stream effectors of the ceramide signal. The implications of this novel lipid signal pathway are discussed.