Differential apoptotic effect and metabolism of N-acetylsphingosine and N-hexanoylsphingosine in CHP-100 human neurotumor cells.
Biochem Biophys Res Commun
; 458(3): 456-461, 2015 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-25656578
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esfingosina
/
Ceramidas
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Apoptose
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Neoplasias Neuroepiteliomatosas
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Células Neuroepiteliais
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2015
Tipo de documento:
Article