Add time:08/23/2019         Source:sciencedirect.com

We report that N-oleoylethanolamine (NOE), widely employed as a ceramidase inhibitor, also inhibits glucosylation of naturally occurring ceramides. When CHP-100 neuroepithelioma cells were exposed for 18h to non-toxic NOE concentrations (i.e. up to 70 μM), basal incorporation of labelled hexose into glucosylceramide (GlcCer) and higher order neutral glycosphingolipids was significantly inhibited. In cells treated with 30μM N-hexanoylsphingosine (C6-Cer), NOE affected only marginally short-chain glucocerebroside accumulation, but markedly decreased accumulation of glucocerebrosides originating from glucosylation of a long-chain ceramide (Lc-Cer) pool produced upon C6-Cer treatment. Evidence is provided that NOE effects neither are mediated by their effects on ceramidase nor are due to enhanced long-chain GlcCer (Lc-GlcCer) conversion to higher order glycosylated derivatives. NOE inhibition of Lc-GlcCer generation was accompanied by enhanced accumulation of Lc-Cer and by potentiation of apoptosis induced by C6-Cer; the possible causal relationships between these two phenomena are discussed.

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