TNFα-Induced IEC-6 Cell Apoptosis Requires Activation of ICE Caspases whereas Complete Inhibition of the Caspase Cascade Leads to Necrotic Cell Death
| Autor: | Serge Dionne, Frank M. Ruemmele, Emile Levy, Ernest G. Seidman |
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| Rok vydání: | 1999 |
| Předmět: |
Programmed cell death
Necrosis Biophysics Apoptosis Cysteine Proteinase Inhibitors Biochemistry Amino Acid Chloromethyl Ketones Cell Line Western blot medicine Animals Humans Molecular Biology Caspase biology medicine.diagnostic_test Tumor Necrosis Factor-alpha Intrinsic apoptosis Cell Biology Flow Cytometry Caspase Inhibitors Rats Cell biology Jejunum Cell culture Caspases biology.protein Tumor necrosis factor alpha Interferons medicine.symptom Cell Division |
| Zdroj: | Biochemical and Biophysical Research Communications. 260:159-166 |
| ISSN: | 0006-291X |
| Popis: | Tumor necrosis factor (TNF)alpha is considered to play a key pathogenetic role in inflammatory bowel diseases. In this study we analyzed the mechanisms by which TNFalpha induces intestinal epithelial cell apoptosis. TNFalpha alone, and more potently in combination with IFNgamma, induced a high degree of IEC-6 cell apoptosis. This effect was more than 100-fold stronger if both of the TNF-R were stimulated, compared to stimulation of the p55-TNF-R alone, indicating an important apoptosis enhancing effect of the p75-TNF-R. TNFalpha-induced apoptosis required activation of ICE caspases and was completely abolished by its inhibitor, zVAD-fmk. Specific inhibition of caspase-3 with zDEVD-fmk did not alter the effect of TNFalpha. Western blot analyses confirmed that caspase-3 was not activated in response to TNFalpha. In the presence of complete inhibition of the caspase cascade with zVAD-fmk (>/=50 microM), TNFalpha induced cell necrosis rather than apoptosis. Our data reveal that TNFalpha can trigger enterocyte cell death via apoptosis or necrosis, depending upon the activation or blockade of specific caspases. |
| Databáze: | OpenAIRE |
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