The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells

Détails

ID Serval
serval:BIB_8D44E3D36666
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta-cells
Périodique
Diabetes
Auteur(s)
Ammendrup  A., Maillard  A., Nielsen  K., Aabenhus Andersen  N., Serup  P., Dragsbaek Madsen  O., Mandrup-Poulsen  T., Bonny  C.
ISSN
0012-1797 (Print)
Statut éditorial
Publié
Date de publication
09/2000
Volume
49
Numéro
9
Pages
1468-76
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Résumé
To characterize the differentiation events that selectively target insulin-producing cells to interleukin (IL)-1beta-induced apoptosis, we studied IL-1beta signaling via mitogen-activated protein kinase (MAPK) and stress-activated protein kinase in 2 pancreatic endocrine cell lines. We studied the glucagon-secreting AN-glu cell line and the insulin and the islet amyloid polypeptide-producing beta-cell line (AN-ins cells), which is derived by stable transfection of AN-glu cells with the transcription factor pancreatic duodenal homeobox factor-1. AN-ins cells were more sensitive to the cytotoxic action of IL-1beta. This increased sensitivity was not associated with a more pronounced IL-l-induced nitric oxide production in AN-ins cells, but it correlated with a more marked activation of the 3 MAPKs extracellular signal-regulated kinases (ERKs)-1/2, c-Jun NH2-terminal kinase (JNK), and p38 MAPK (p38). This led to increased phosphorylation of the transcription factors c-Jun, Elk-1, and ATF2 and of heat shock protein 25. Inhibition of ERK-1/2 and p38 did not prevent but aggravated IL-1beta-induced cell death. In contrast, inhibition of JNK by transfection with the dominant negative inhibitor of the JNK-binding domain prevented apoptosis in both cell types. Cell death could be elicited by overexpressing the catalytic domain of MAPK kinase kinase 1, a specific activator of JNK and nuclear factor-kappaB, which does not recruit ERK-1/2 or p38. Coactivation of ERK-1/2 with JNK did not prevent apoptosis. In conclusion, increased MAPK signaling in response to IL-1beta may represent a novel molecular marker of beta-cell differentiation. JNK inhibition represents an effective means of preventing IL-1beta-activated beta-cell destruction.
Mots-clé
Apoptosis/drug effects/*physiology Cell Differentiation/*physiology Cell Line Homeodomain Proteins/metabolism Humans Interleukin-1/*pharmacology Islets of Langerhans/*cytology/drug effects/*physiology JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/*metabolism/*pharmacology Nitric Oxide/metabolism Protein-Serine-Threonine Kinases/metabolism Recombinant Proteins/metabolism/pharmacology Trans-Activators/metabolism Transfection p38 Mitogen-Activated Protein Kinases
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:16
Dernière modification de la notice
08/05/2019 21:48
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