N-oleoylethanolamine inhibits glucosylation of natural ceramides in CHP-100 neuroepithelioma cells: Possible implications for apoptosis

We report that N-oleoylethanolamine (NOE), widely employed as a ceramidase inhibitor, also inhibits glucosylation of naturally occurring ceramides. Wh en CHP-100 neuroepithelioma cells were exposed for 18h to non-toxic NOE con centrations (i.e. up to 70 mu M), basal incorporation of labelled hexose in to glucosylceramide (GlcCer) and higher order neutral glycosphingolipids wa s significantly inhibited. In cells treated with 30 mu M N-hexanoylsphingos ine (C-6-Cer), NOE affected only marginally short-chain glucocerebroside ac cumulation, but markedly decreased accumulation of glucocerebrosides origin ating from glucosylation of a long-chain ceramide (Lc-Cer) pool produced up on C-6-Cer treatment. Evidence is provided that NOE effects neither are med iated by their effects on ceramidase nor are due to enhanced long-chain Glc Cer (Lc-GlcCer) conversion to higher order glycosylated derivatives. NOE in hibition of Lc-GlcCer generation was accompanied by enhanced accumulation o f Lc-Cer and by potentiation of apoptosis induced by C-6-Cer; the possible causal relationships between these two phenomena are discussed. (C) 1999 Ac ademic Press.