Caspase-dependent apoptosis induced by okadaic acid (OA) in CHP-100 neuroepithelioma cells has previously been shown to associate with a rapid and sustained elevation in intracellular ceramide concentration. We now report that treatment of CHP-100 cells with OA also evoked a rapid elevation in glucosylceramide levels that was maintained at steady state as cells underwent apoptosis; moreover, as observed for ceramide, OA-induced glucosylceramide accumulation was not blocked by fumonisin B-1. Remarkably, when cell death was prevented by caspase inhibition, glucosylceramide accumulation was potentiated and ceramide elevation reduced, thus suggesting that, during apoptosis completion, accumulation of ceramide was partly driven by impairment of its glucosylation through a caspase-dependent mechanism. We studied whether ceramide glucosylation provided a mechanism for negative modulation of OA-induced apoptosis. We observed that the blocking of glucosylceramide synthesis markedly potentiated OA-induced ceramide elevation, but neither accelerated apoptosis onset nor potentiated the apoptotic response. These results indicate that modulation of ceramide glucosylation does not affect the apoptotic response to okadaic acid and suggest that caution must be exercised concerning the possibility that ceramide plays a key role in apoptosis induction. (C) 2001 Elsevier Science Inc. All rights reserved.
Di Bartolomeo S., S.A. (2001). Potentiation of okadaic acid-induced ceramide elevation but not apoptosis by inhibition of glucosylceramide synthase in human neuroepithelioma cells. BIOCHEMICAL PHARMACOLOGY, 61(7), 851-856.
|Tipologia:||Articolo su rivista|
|Citazione:||Di Bartolomeo S., S.A. (2001). Potentiation of okadaic acid-induced ceramide elevation but not apoptosis by inhibition of glucosylceramide synthase in human neuroepithelioma cells. BIOCHEMICAL PHARMACOLOGY, 61(7), 851-856.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/09|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0006-2952(01)00569-X|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2001|
|Titolo:||Potentiation of okadaic acid-induced ceramide elevation but not apoptosis by inhibition of glucosylceramide synthase in human neuroepithelioma cells|
|Autori:||Di Bartolomeo S., Spinedi A.|
|Appare nelle tipologie:||01 - Articolo su rivista|