The cross roles of sphingosine kinase 1/2 and ceramide glucosyltransferase in cell growth and death.

Sphingosine-1-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1in mouse skin fibroblasts. However, in SK2 cells, SK1 expression was markedly increased to SK2 levels whereas in SK1 cells, SK2 expression was unaffected. Ceramide, glucosylceramide and sphingosine levels were all increased in SK1 but less so in SK2 cells and S1P levels were not significantly reduced in either SK1 or SK2 cells.

Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia.

Hypoxia has been previously shown to inhibit the dihydroceramide (DHC) desaturase, leading to the accumulation of DHC. In this study, we used metabolic labeling with [3H]-palmitate, HPLC/MS/MS analysis, and specific inhibitors to show numerous sphingolipid changes after oxygen deprivation in cerebral microendothelial cells. The increased DHC, particularly long-chain forms, was observed in both whole cells and detergent-resistant membranes.

Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons.

Neurons (both primary cultures of 3-day rat hippocampal neurons and embryonic chick neurons) rapidly converted exogenous NBD-sphingomyelin (SM) to NBD-Cer but only slowly converted NBD-Cer to NBD-SM. This was confirmed by demonstrating low in vitro sphingomyelin synthase (SMS) and high sphingomyelinase (SMase) activity in neurons. Similar results were observed in a human neuroblastoma cell line (LA-N-5).