Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Long-chain ceramide produced in response to N-hexanoylsphingosine does not induce apoptosis in CHP-100 cells. 1978 83

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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PMID:Differential apoptotic effect and metabolism of N-acetylsphingosine and N-hexanoylsphingosine in CHP-100 human neurotumor cells. 2565 78