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 (C6-Cer) in CHP-100 human neuroepithelioma cells associates with accumulation of monohexosylsphingolipids produced not only by short-chain ceramide glycosylation but also through glycosylation of a ceramide pool endogenously produced. By high-performance thin layer chromatography on borate silica gel plates, newly formed monohexosylsphingolipids were identified as glucosylceramides (GluCer); however, accumulation of lactosylceramide or higher-order glycosphingolipids was not observed. GluCer accumulation was fully suppressed by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol; moreover, while this inhibitor had no effect on cell viability when administered alone, it markedly potentiated the apoptotic effect of C6-Cer. These results provide evidence that activation of GluCer synthesis is an important mechanism through which CHP-100 cells attempt to escape ceramide-induced apoptosis.
Spinedi
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Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy.
Bartolomeo
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Piacentini
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D017209:Apoptosis; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D005963:Glucosylceramides / Q000096:biosynthesis* / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D014407:Tumor Cells, Cultured
D002518:Ceramides; D005963:Glucosylceramides; D006028:Glycosphingolipids; C101954:N-caproylsphingosine