Divergent role of ceramide generated by exogenous sphingomyelinases on NF-κB activation and apoptosis in human colon HT-29 cells
- 1 August 2002
- journal article
- Published by Wiley in FEBS Letters
- Vol. 526 (1-3) , 15-20
- https://doi.org/10.1016/s0014-5793(02)03106-x
Abstract
This study examined the role of ceramide generated by exogenous sphingomyelinases (SMases) on transcription nuclear factor-κB (NF-κB) activation and apoptosis in human colon epithelial HT-29 cells. Exogenous neutral (N) and acidic (A) SMase activated NF-κB with different kinetics, accounting for the diverse pattern of DNA binding of NF-κB complexes activated by tumor necrosis factor-α (TNF). NSMase activated predominantly RelA/p52 and RelA/p50 dimers within 30 min, while ASMase activated the p50/p50 homodimer by 20 h. The predominant activation of RelA-containing κB complexes by TNF or NSMase paralleled the induction of interleukin-8. HT-29 cells were sensitive to ASMase and TNF but resistant to NSMase. However, the apoptotic potential of NSMase was masked by NF-κB, as its prior inactivation sensitized HT-29 cells to NSMase. Thus, the generation of ceramide by exogenous SMases participates differentially in inflammation and apoptosis. © 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.The work presented was supported by the Research Center for Liver and Pancreatic Diseases, P50 AA11999, funded by the U.S. National Institute on Alcohol Abuse and Alcoholism, Plan Nacional de I+D, Grants SAF 99-0138, 2FD97-0988, SAF01-2118 and Fondo de Investigaciones Sanitarias FIS 00-907Peer RevieweKeywords
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