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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- 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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