N-Oleoylethanolamine inhibits glucosylation of natural ceramides in CHP-100 neuroepithelioma cells: possible implications for apoptosis.

Abstract

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.

• Authors: A Spinedi, S Di Bartolomeo, M Piacentini
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 255 Issue 2 Pg. 456-9 (Feb 16 1999) ISSN: 0006-291X [Print] United States
• PMID: 10049730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1999 Academic Press.

Chemical References

• Antigens, CD
• Carbon Radioisotopes
• Ceramides
• Endocannabinoids
• Enzyme Inhibitors
• Ethanolamines
• Lactosylceramides
• Oleic Acids
• N-oleoylethanolamine
• Palmitic Acid
• CDw17 antigen
• Amidohydrolases
• Ceramidases

Topics

• Acylation (drug effects)
• Amidohydrolases (antagonists & inhibitors)
• Antigens, CD
• Apoptosis (drug effects)
• Carbon Radioisotopes (metabolism)
• Ceramidases
• Ceramides (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Endocannabinoids
• Enzyme Inhibitors (pharmacology)
• Ethanolamines (pharmacology)
• Glycosylation
• Humans
• Lactosylceramides (metabolism, physiology)
• Neuroectodermal Tumors, Primitive, Peripheral (metabolism, pathology)
• Oleic Acids
• Palmitic Acid (metabolism)
• Tumor Cells, Cultured