APOPTOSIS INDUCED BY N-HEXANOYLSPHINGOSINE IN CHP-100 CELLS ASSOCIATES WITH ACCUMULATION OF ENDOGENOUS CERAMIDE AND IS POTENTIATED BY INHIBITION OF GLUCOCEREBROSIDE SYNTHESIS

We report that apoptosis induced by N-hexanoylsphingosine (C-6-Cer)in CHP-100 human neuroepithelioma cells associates with accumulation of m onohexosylsphingolipids produced not only by short-chain ceramide glyc osylation but also through glycosylation of a ceramide pool endogenous ly produced. By high-performance thin layer chromatography on berate s ilica gel plates, newly formed monohexosylsphingolipids were identifie d as glucosylceramides (GluCer); however, accumulation of lactosylcera mide or higher-order glycosphingolipids was not observed. GluCer accum ulation was fully suppressed by -1-phenyl-2-decanoylamino-3-morpholino -1-propanol; moreover, while this inhibitor had no effect on cell viab ility when administered alone, it markedly potentiated the apoptotic e ffect of C-6-Cer. These results provide evidence that activation of Gl uCer synthesis is an important mechanism through which CHP-100 cells a ttempt to escape ceramide-induced apoptosis.