Ceramide generation by two distinct pathways in tumor necrosis factor α‐induced cell death

FEBS Letters

Idriss, Nadine Z¹  Liu, Bin⁴  El-Sabban, Marwan³  Dbaibo, Ghassan S¹  Krikorian, Armand¹  Perry, David K⁵  El-Assaad, Wissal¹  Hannun, Yusuf A⁵  Diab, Karim¹  Driscoll, Timothy A² 

[1] Department of Pediatrics, American University of Beirut, Beirut, Lebanon;Department of Pediatrics, Duke University, Durham, NC 27710, USA;Department of Human Morphology, American University of Beirut, Beirut, Lebanon;Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute for Environmental Health Sciences, Research Triangle Park, NC 27709, USA;Department of Biochemistry and Molecular Biology, Medical College of South Carolina, Charleston, SC 29425, USA

关键词: Cell death;    Apoptosis;    Ceramide;    Sphingomyelinase;    Ceramide synthase;    TNFα;    tumor necrosis factor α;    N-SMase;    neutral sphingomyelinase;    GSH;    glutathione;    FB1;    fumonisin B1;    ROI;    reactive oxygen intermediate;   

DOI  :  10.1016/S0014-5793(01)02625-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown