The cytotoxic effects of N-acetylsphingosine (C2-Cer) and N-hexanoylsphingosine (C6-Cer) were compared together with their specific intracellular accumulation profiles and metabolism in human CHP-100 neuroepithelioma cells. The two short-chain ceramides, administered in the culture medium at an equimolar concentration, evoked a differential apoptotic response, with C6-Cer showing markedly more cytotoxic than C2-Cer. Apoptosis, that was suppressed in both cases by inhibition of caspase-9, but not of caspase-8, associated with a higher intracellular accumulation of C6-Cer over C2-Cer, notwithstanding C6-Cer was actively metabolized by direct glucosylation or by conversion to natural ceramide via the sphingosine salvage pathway, whereas C2-Cer was apparently metabolically inhert. C2-Cer cytotoxicity was markedly enhanced by increasing its concentration in the culture medium, and this response associated with a higher intracellular accumulation of this compound, in the absence of any natural ceramide elevation. These results support the notion that the differential apoptotic effect evoked by C2-Cer and C6-Cer in CHP-100 cells is driven by their differential intracellular accumulation profiles, but not by their differential property to generate natural ceramide via the sphingosine salvage pathway.

DI BARTOLOMEO, S., Agostini, A., Spinedi, A. (2015). Differential apoptotic effect and metabolism of N-acetylsphingosine and N-hexanoylsphingosine in CHP-100 human neurotumor cells. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 458(3), 456-461 [10.1016/j.bbrc.2015.01.107].

Differential apoptotic effect and metabolism of N-acetylsphingosine and N-hexanoylsphingosine in CHP-100 human neurotumor cells

DI BARTOLOMEO, SABRINA;SPINEDI, ANGELO
2015-03-01

Abstract

The cytotoxic effects of N-acetylsphingosine (C2-Cer) and N-hexanoylsphingosine (C6-Cer) were compared together with their specific intracellular accumulation profiles and metabolism in human CHP-100 neuroepithelioma cells. The two short-chain ceramides, administered in the culture medium at an equimolar concentration, evoked a differential apoptotic response, with C6-Cer showing markedly more cytotoxic than C2-Cer. Apoptosis, that was suppressed in both cases by inhibition of caspase-9, but not of caspase-8, associated with a higher intracellular accumulation of C6-Cer over C2-Cer, notwithstanding C6-Cer was actively metabolized by direct glucosylation or by conversion to natural ceramide via the sphingosine salvage pathway, whereas C2-Cer was apparently metabolically inhert. C2-Cer cytotoxicity was markedly enhanced by increasing its concentration in the culture medium, and this response associated with a higher intracellular accumulation of this compound, in the absence of any natural ceramide elevation. These results support the notion that the differential apoptotic effect evoked by C2-Cer and C6-Cer in CHP-100 cells is driven by their differential intracellular accumulation profiles, but not by their differential property to generate natural ceramide via the sphingosine salvage pathway.
mar-2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/09 - FISIOLOGIA
English
Con Impact Factor ISI
N-Acetylsphingosine; N-Hexanoylsphingosine; Long-Chain Ceramide; Sphingosine salvage pathway: Apoptosis
DI BARTOLOMEO, S., Agostini, A., Spinedi, A. (2015). Differential apoptotic effect and metabolism of N-acetylsphingosine and N-hexanoylsphingosine in CHP-100 human neurotumor cells. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 458(3), 456-461 [10.1016/j.bbrc.2015.01.107].
DI BARTOLOMEO, S; Agostini, A; Spinedi, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/110827
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