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Ceramide generation by two distinct pathways in tumor necrosis factor α‐induced cell death
Author(s) -
Dbaibo Ghassan S,
El-Assaad Wissal,
Krikorian Armand,
Liu Bin,
Diab Karim,
Idriss Nadine Z,
El-Sabban Marwan,
Driscoll Timothy A,
Perry David K,
Hannun Yusuf A
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02625-4
Subject(s) - ceramide , sphingomyelin , lipid signaling , programmed cell death , microbiology and biotechnology , sphingomyelin phosphodiesterase , ceramide synthase , second messenger system , tumor necrosis factor alpha , biology , chemistry , signal transduction , biochemistry , apoptosis , immunology , enzyme , membrane
Ceramide accumulation in the cell can occur from either hydrolysis of sphingomyelin or by de novo synthesis. In this study, we found that blocking de novo ceramide synthesis significantly inhibits ceramide accumulation and subsequent cell death in response to tumor necrosis factor α. When cells were pre‐treated with glutathione, a proposed cellular regulator of neutral sphingomyelinase, inhibition of ceramide accumulation at early time points was achieved with attenuation of cell death. Inhibition of both pathways achieved near‐complete inhibition of ceramide accumulation and cell death indicating that both pathways of ceramide generation are stimulated. This illustrates the complexity of ceramide generation in cytokine action.