The JNK binding domain of islet-brain 1 inhibits IL-1 induced JNK activity and apoptosis but not the transcription of key proapoptotic or protective genes in insulin-secreting cell lines.

Détails

ID Serval
serval:BIB_506CF7D2B81D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The JNK binding domain of islet-brain 1 inhibits IL-1 induced JNK activity and apoptosis but not the transcription of key proapoptotic or protective genes in insulin-secreting cell lines.
Périodique
Cytokine
Auteur(s)
Nikulina M.A., Sandhu N., Shamim Z., Andersen N.A., Oberson A., Dupraz P., Thorens B., Karlsen A.E., Bonny C., Mandrup-Poulsen T.
ISSN
1043-4666[print], 1043-4666[linking]
Statut éditorial
Publié
Date de publication
2003
Volume
24
Numéro
1-2
Pages
13-24
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The stress-activated protein kinase c-Jun NH2-terminal kinase (JNK) is a central signal for interleukin-1beta (IL-1beta)-induced apoptosis in insulin-producing beta-cells. The cell-permeable peptide inhibitor of JNK (JNKI1), that introduces the JNK binding domain (JBD) of the scaffold protein islet-brain 1 (IB1) inside cells, effectively prevents beta-cell death caused by this cytokine. To define the molecular targets of JNK involved in cytokine-induced beta-cell apoptosis we investigated whether JNKI1 or stable expression of JBD affected the expression of selected pro- and anti-apoptotic genes induced in rat (RIN-5AH-T2B) and mouse (betaTC3) insulinoma cells exposed to IL-1beta. Inhibition of JNK significantly reduced phosphorylation of the specific JNK substrate c-Jun (p<0.05), IL-1beta-induced apoptosis (p<0.001), and IL-1beta-mediated c-fos gene expression. However, neither JNKI1 nor JBD did influence IL-1beta-induced NO synthesis or iNOS expression or the transcription of the genes encoding mitochondrial manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase rho (GSTrho), heat shock protein (HSP) 70, IL-1beta-converting enzyme (ICE), caspase-3, apoptosis-inducing factor (AIF), Bcl-2 or Bcl-xL. We suggest that the anti-apoptotic effect of JNK inhibition by JBD is independent of the transcription of major pro- and anti-apoptotic genes, but may be exerted at the translational or posttranslational level.
Mots-clé
Adaptor Proteins, Signal Transducing, Animals, Apoptosis/physiology, Binding Sites, Insulin/metabolism, Interleukin-1/metabolism, Islets of Langerhans/metabolism, JNK Mitogen-Activated Protein Kinases, Mice, Mitogen-Activated Protein Kinases/metabolism, Nitric Oxide, Nitric Oxide Synthase/metabolism, Nuclear Proteins/metabolism, Protein Structure, Tertiary, Rats, Trans-Activators/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 14:41
Dernière modification de la notice
03/03/2018 17:08
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