title: Brefeldin A limits N-hexanoylsphingosine-induced accumulation of natural ceramide via the salvage pathway by enhancing glucosylation.
abstract: Cells actively metabolize exogenously administered N-hexanoylsphingosine (C6-Cer) to natural (i.e. long-chain) ceramide (LC-Cer) via the sphingosine (Sph) salvage pathway, namely via C6-Cer deacylation and Sph reacylation with a long-chain fatty acid. Based on the observation that the mycotoxin brefeldin A (BFA), a Golgi complex disassembler, impairs C6-Cer-evoked LC-Cer accumulation, it has been hypothesized that the integrity of the above-mentioned organelle might be necessary for C6-Cer processing via the salvage pathway and that BFA might block the phenomenon at the step short-chain ceramide deacylation. The present study shows that BFA indeed attenuates C6-Cer-evoked LC-Cer accumulation in human neurotumor CHP-100 cells: evidence is however provided that the phenomenon is not due to impaired synthesis of LC-Cer, but to its enhanced conversion to glucosylceramide. The possibility is discussed that this outcome might be a consequence of the BFA well-established property to induce the merging of the cis-Golgi region with endoplasmic reticulum, namely the compartments in which glucosylceramide synthase and ceramide synthases have been reported to reside.
authors.affiliation: Dipartimento di Biologia, Università di Roma 'Tor Vergata', Via della Ricerca Scientifica 1, 00133, Rome, Italy, spinedi@uniroma2.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Spinedi
mesh_terms: D020126:Brefeldin A / Q000378:metabolism*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D005963:Glucosylceramides / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009183:Mycotoxins / Q000378:metabolism*; D013110:Sphingosine / Q000378:metabolism
chemical_list: D002518:Ceramides; D005963:Glucosylceramides; D009183:Mycotoxins; C101954:N-caproylsphingosine; D020126:Brefeldin A; D013110:Sphingosine