Long-chain ceramide produced in response to N-hexanoylsphingosine does not induce apoptosis in CHP-100 cells.
It has been previously reported that treatment of CHP-100 human neuroepithelioma cells with N-hexanoylsphingosine (C6-Cer) induces intracellular accumulation of long-chain ceramide (LC-Cer) and apoptosis. Herein, we investigated the existence of any causal relationship between the two phenomena. We report that C6-Cer-evoked LC-Cer accumulation is potently attenuated by the ceramide synthase inhibitor fumonisin B1; however, fumonisin B1 neither affects the apoptotic response evoked by C6-Cer administration, nor is toxic by itself to CHP-100 cells. Different to fumonisin B1, the serine-palmitoyltransferase inhibitor L: -cycloserine does not attenuate C6-Cer-evoked LC-Cer accumulation, thus suggesting that LC-Cer is produced via the sphingosine salvage pathway. Consistently, CHP-100 cells accumulate LC-Cer in response to sphingosine administration; however, their viability is not affected. The above-reported results indicate that, in the cell system investigated, C6-Cer, but not LC-Cer, is involved in apoptosis induction. As this finding is discussed in the light of the evidence that C6-Cer-induced apoptosis associates with cytochrome c release into the cytosol and caspase-9 activation, thus calling for an involvement of the mitochondrial pathway, it also lends support to the notion that caution must be exercised when investigating the biological effects of endogenous ceramide by use of exogenously administered short-chain analogues.
Dipartimento Di Biologia, Università Di Roma 'Tor Vergata', Via Della Ricerca Scientifica 1, 00133, Rome, Italy.
Adriano
A
Mancinetti
Sabrina
S
Di Bartolomeo
Angelo
A
Spinedi
D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans
D002518:Ceramides; C101954:N-caproylsphingosine; D053453:Caspase 9