|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
doi: 10.1242/10.1242/jcs.00356
Research Article |
1 Department of Internal Medicine, CHUV-1011 Lausanne, Switzerland
2 Institute of Pharmacology and Toxicology, University Hospital, CHUV-1011
Lausanne, Switzerland
Author for correspondence (e-mail:
jhaeflig{at}chuv.hospvd.ch)
Accepted 7 January 2003
In insulin-secreting cells, cytokines activate the c-Jun N-terminal kinase
(JNK), which contributes to a cell signaling towards apoptosis. The JNK
activation requires the presence of the murine scaffold protein
JNK-interacting protein 1 (JIP-1) or human Islet-brain 1(IB1), which organizes
MLK3, MKK7 and JNK for proper signaling specificity. Here, we used
adenovirus-mediated gene transfer to modulate IB1/JIP-1 cellular content in
order to investigate the contribution of IB1/JIP-1 to ß-cell survival.
Exposure of the insulin-producing cell line INS-1 or isolated rat pancreatic
islets to cytokines (interferon-
, tumor necrosis factor-
and
interleukin-1ß) induced a marked reduction of IB1/JIP-1 content and a
concomitant increase in JNK activity and apoptosis rate. This JNK-induced
pro-apoptotic program was prevented in INS-1 cells by overproducing IB1/JIP-1
and this effect was associated with inhibition of caspase-3 cleavage.
Conversely, reducing IB1/JIP-1 content in INS-1 cells and isolated pancreatic
islets induced a robust increase in basal and cytokine-stimulated apoptosis.
In heterozygous mice carrying a selective disruption of the IB1/JIP-1 gene,
the reduction in IB1/JIP-1 content in happloinsufficient isolated pancreatic
islets was associated with an increased JNK activity and basal apoptosis.
These data demonstrate that modulation of the IB1-JIP-1 content in ß
cells is a crucial regulator of JNK signaling pathway and of cytokine-induced
apoptosis.
Key words: Type-I diabetes, ß-Cell line, Islet-brain-1, IB1/JIP-1, INS-1, Pancreatic islets, Apoptosis, Adenovirus, JNK activity
This article has been cited by other articles:
|
|
 |
|
  D. Mokhtari, J. W. Myers, and N. Welsh The MAPK Kinase Kinase-1 Is Essential for Stress-Induced Pancreatic Islet Cell Death Endocrinology, June 1, 2008; 149(6): 3046 - 3053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Maedler, F. T. Schulthess, C. Bielman, T. Berney, C. Bonny, M. Prentki, M. Y. Donath, and R. Roduit Glucose and leptin induce apoptosis in human {beta}-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases FASEB J, June 1, 2008; 22(6): 1905 - 1913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ferdaoussi, S. Abdelli, J.-Y. Yang, M. Cornu, G. Niederhauser, D. Favre, C. Widmann, R. Regazzi, B. Thorens, G. Waeber, et al. Exendin-4 Protects {beta}-Cells From Interleukin-1{beta}-Induced Apoptosis by Interfering With the c-Jun NH2-Terminal Kinase Pathway Diabetes, May 1, 2008; 57(5): 1205 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jaeschke, M. Rincon, B. Doran, J. Reilly, D. Neuberg, D. L. Greiner, L. D. Shultz, A. A. Rossini, R. A. Flavell, and R. J. Davis Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes PNAS, May 10, 2005; 102(19): 6931 - 6935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Storling, N. Allaman-Pillet, A. E. Karlsen, N. Billestrup, C. Bonny, and T. Mandrup-Poulsen Antitumorigenic Effect of Proteasome Inhibitors on Insulinoma Cells Endocrinology, April 1, 2005; 146(4): 1718 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuda, K. Ferreri, I. Todorov, Y. Kuroda, C. V. Smith, F. Kandeel, and Y. Mullen Silymarin Protects Pancreatic {beta}-Cells against Cytokine-Mediated Toxicity: Implication of c-Jun NH2-Terminal Kinase and Janus Kinase/Signal Transducer and Activator of Transcription Pathways Endocrinology, January 1, 2005; 146(1): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Abe, K. Murao, H. Imachi, W. M. Cao, X. Yu, K. Yoshida, N. C. W. Wong, M. A. Shupnik, J.-A. Haefliger, G. Waeber, et al. Thyrotropin-Releasing Hormone-Stimulated Thyrotropin Expression Involves Islet-Brain-1/c-Jun N-Terminal Kinase Interacting Protein-1 Endocrinology, December 1, 2004; 145(12): 5623 - 5628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yoshioka Scaffold Proteins in Mammalian MAP Kinase Cascades J. Biochem., June 1, 2004; 135(6): 657 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Abderrahmani, G. Niederhauser, V. Plaisance, M.-E. Roehrich, V. Lenain, T. Coppola, R. Regazzi, and G. Waeber Complexin I regulates glucose-induced secretion in pancreatic {beta}-cells J. Cell Sci., May 1, 2004; 117(11): 2239 - 2247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Mooney and A. J. Whitmarsh Docking Interactions in the c-Jun N-terminal Kinase Pathway J. Biol. Chem., March 19, 2004; 279(12): 11843 - 11852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Martin, T. Tawadros, L. Meylan, A. Abderrahmani, D. F. Condorelli, G. Waeber, and J.-A. Haefliger Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines J. Biol. Chem., December 26, 2003; 278(52): 53082 - 53089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ling, M. Van de Casteele, J. Dong, H. Heimberg, J.-A. Haefliger, G. Waeber, F. Schuit, and D. Pipeleers Variations in IB1/JIP1 Expression Regulate Susceptibility of {beta}-Cells to Cytokine-Induced Apoptosis Irrespective of C-Jun NH2-Terminal Kinase Signaling Diabetes, October 1, 2003; 52(10): 2497 - 2502. [Abstract] [Full Text] [PDF]
|
|
