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Apoptotic Signal of Fas Is Not Mediated by Ceramide

Shu-Ching Hsu, Chia-Cheng Wu, Tien-Yau Luh, Chen-Kung Chou, Shau-Hwa Han, and Ming-Zong Lai

From the Graduate Institute of Microbiology, National Taiwan University School of Medicine, Taiwan, China; the Institute of Molecular Biology, Academia Sinica, Taiwan, China; the Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taiwan, China; the Department of Chemistry, National Taiwan University, Taiwan, China; and the Department of Medical Research, Veteran General Hospital, Taipei, Taiwan, China.

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-kappa B 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.

Blood, Vol. 91 No. 8 (April 15), 1998: pp. 2658-2663
© 1998 by The American Society of Hematology.


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