title: Apoptotic signal of Fas is not mediated by ceramide.
abstract: Ceramide has been suggested as the secondary messenger mediating the apoptotic signal for Fas engagement. By using different inhibitors, we demonstrated here that ceramide is unlikely a mediator of Fas-initiated apoptosis. First, cAMP prevented cell death induced by ceramide but not by Fas. Second, ceramide-triggered, but not Fas-triggered, apoptosis was antagonized by the free radical scavenger C60. Third, the metal chelator pyrrolidinedithiocarbamate suppressed ceramide-initiated DNA fragmentation but had no effect on the Fas-induced cell death. Fourth, the SAPK/ERK kinase dominant negative mutant, which attenuated ceramide-induced cell death, did not prevent Fas-induced apoptosis. Finally, activation of NF-kappaB inhibited ceramide-induced but not Fas-initiated apoptosis. The fact that many antagonists of ceramide-induced apoptosis could not suppress Fas-mediated cell death clearly indicates that ceramide is not the mediator for Fas-initiated apoptotic signal.
authors.affiliation: Graduate Institute of Microbiology, National Taiwan University School of Medicine, Taiwan, China.
authors.forename: S C
authors.initials: SC
authors.lastname: Hsu
authors.forename: C C
authors.initials: CC
authors.lastname: Wu
authors.forename: T Y
authors.initials: TY
authors.lastname: Luh
authors.forename: C K
authors.initials: CK
authors.lastname: Chou
authors.forename: S H
authors.initials: SH
authors.lastname: Han
authors.forename: M Z
authors.initials: MZ
authors.lastname: Lai
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002518:Ceramides / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
chemical_list: D002518:Ceramides; D016328:NF-kappa B; D019014:fas Receptor