Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling.

Détails

ID Serval
serval:BIB_78FD74B434BB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling.
Périodique
Diabetes
Auteur(s)
Ling Z., Van de Casteele M., Dong J., Heimberg H., Haefliger J.A., Waeber G., Schuit F., Pipeleers D.
ISSN
0012-1797
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
52
Numéro
10
Pages
2497-502
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
We previously reported that interleukin-1beta (IL-1beta) alone does not cause apoptosis of beta-cells, whereas when combined with gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), it exerts a distinct apoptotic effect. Studies in beta-cell lines indicated that IL-1beta reduced expression of islet brain (IB)-1/JNK interacting protein (JIP)-1, a JNK scaffold protein with antiapoptotic action. We examined whether variations in IB1/JIP-1 expression in purified primary beta-cells affect their susceptibility to cytokine-induced apoptosis. Exposure to IL-1beta for 24 h decreased cellular IB1/JIP-1 content by 66 +/- 17%; this IL-1beta effect was maintained in the presence of TNF-alpha + IFN-gamma, which did not influence IB1/JIP-1 levels by themselves. Addition of IL-1beta to TNF-alpha + IFN-gamma increased apoptosis from 20 +/- 2% to 59 +/- 5%. A similar increase in TNF-alpha + IFN-gamma-induced apoptosis was produced by adenoviral expression of antisense IB1/JIP-1 and was not further enhanced by addition of IL-1beta, indicating that IL-1beta-mediated suppression of IB1/JIP-1 in beta-cells increases their susceptibility to cytokine-induced apoptosis. However, adenovirally mediated overexpression of IB1/JIP-1 also potentiated TNF-alpha + IFN-gamma-induced apoptosis, suggesting that the antiapoptotic effect of IB1/JIP-1 depends on well-defined cellular levels. We conclude that the IB1/JIP-1 level in beta-cells can control their susceptibility to apoptosis independent of JNK signaling.
Mots-clé
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Carrier Proteins, Cells, Cultured, Cytokines, Drug Administration Schedule, Drug Combinations, Drug Synergism, Gene Transfer Techniques, Humans, Interferon-gamma, Interleukin-1, Islets of Langerhans, JNK Mitogen-Activated Protein Kinases, Male, Mitogen-Activated Protein Kinases, Nuclear Proteins, Rats, Rats, Wistar, Recombinant Proteins, Signal Transduction, Trans-Activators, Tumor Necrosis Factor-alpha
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 14:48
Dernière modification de la notice
20/08/2019 15:35
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