Fig. 5.

Schematic of sphingolipid signaling and pharmacological manipulations used in this study. Sphingomyelin is a major lipid component of the cell membrane. Ceramide species are generated from sphingomyelin via the action of sphingomyelinase (SMASE), which is increased by p75 activation. Ceramide is freely interconverted between various signaling lipids in a manner dependent upon the activity of each enzyme. For example, on activation of SMASE intracellular ceramide levels increase, leading to increased sphingosine levels via the action of ceramidase, which converts ceramide to sphingosine. Conversely, increased sphingosine levels will lead to increased ceramide via sphingosine conversion by ceramide synthase. Application of the sphingomyelinase inhibitor sphingolactone-24 blocks the endogenous generation of ceramide and therefore also reduces the other sphingolipid signaling species. Fumonisin B1 blocks the activity of ceramide synthase, inhibiting the conversion of sphingosine to ceramide. However, ceramidase will convert intracellular ceramide to sphingosine; therefore fumonisin B1 application leads to a depletion of ceramide and an increase in sphingosine species.