The Susceptibility to Fas-Induced Apoptosis in Normal Enterocytes Is Regulated on the Level of cIAP1 and 2

Various members of the tumor necrosis factor receptor superfamily are implicated in the regulation of enterocyte apoptosis. Previously, we observed that human intestinal epithelial cells are rather unsusceptible to Fas-induced apoptosis. In the present study we analyzed these protective mechanisms i...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-02, Vol.290 (4), p.1308-1314
Main Authors: Ruemmele, F.M., Beaulieu, J.F., O'Connell, J., Bennett, M.W., Seidman, E.G., Lentze, M.J.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis - physiology
Carrier Proteins - genetics
Carrier Proteins - metabolism
CASP8 and FADD-Like Apoptosis Regulating Protein
Caspase 3
Caspase 8
Caspase 9
Caspases - genetics
Caspases - metabolism
Cell Line
Cycloheximide - pharmacology
Down-Regulation
Enterocytes - cytology
Enterocytes - metabolism
fas Receptor - genetics
fas Receptor - metabolism
Fas-Associated Death Domain Protein
Humans
Inhibitor of Apoptosis Proteins
Intracellular Signaling Peptides and Proteins
Leupeptins - pharmacology
NF-kappa B - metabolism
Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Ubiquitin-Protein Ligases
Up-Regulation
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Summary:Various members of the tumor necrosis factor receptor superfamily are implicated in the regulation of enterocyte apoptosis. Previously, we observed that human intestinal epithelial cells are rather unsusceptible to Fas-induced apoptosis. In the present study we analyzed these protective mechanisms in the human intestinal epithelial cell line HIEC, focusing on antiapoptotic molecules of the IAP family which block apoptosis at the level of the caspase cascade. HIEC expressed all key molecules required to trigger Fas-induced apoptosis. However, no apoptosis occurred after activation of Fas, whereas an upregulation of antiapoptotic cIAP1 and 2 was observed. Suppression of this upregulation with the proteasome inhibitor MG132 or the protein synthesis inhibitor cycloheximide highly sensitized HIEC toward Fas-induced apoptosis. Western blot analyses revealed that both inhibitors potently suppressed endogenously produced cIAP1 and 2. No effect was observed on XIAP expression. These data indicate that enterocytes are particularly protected against Fas-induced apoptosis on the level of executionary caspases.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2002.6348