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. When CHP-100 neuroepithelioma cells were exposed for 18h to non-toxic NOE concentrations (i.e. up to 70 microM), basal incorporation of labelled hexose into glucosylceramide (GlcCer) and higher order neutral glycosphingolipids was significantly inhibited. In cells treated with 30 microM 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.
Spinedi
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A
Department of Biology, University of Rome 'Tor Vergata', Italy. spinedi@uniroma2.it
Di Bartolomeo
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S
Piacentini
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M
D000215:Acylation / Q000187:drug effects; D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects*; D002250:Carbon Radioisotopes / Q000378:metabolism; D055572:Ceramidases; D002518:Ceramides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D007790:Lactosylceramides / Q000378:metabolism / Q000502:physiology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism* / Q000473:pathology; D009829:Oleic Acids; D019308:Palmitic Acid / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D002250:Carbon Radioisotopes; D002518:Ceramides; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D007790:Lactosylceramides; D009829:Oleic Acids; C033595:N-oleoylethanolamine; D019308:Palmitic Acid; C009744:CDw17 antigen; D000581:Amidohydrolases; D055572:Ceramidases