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Diabetologia
Published in: Diabetologia 9/2009

01-09-2009 | Article

JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis

Authors: S. Abdelli, J. Puyal, C. Bielmann, V. Buchillier, A. Abderrahmani, P. G. H. Clarke, J. S. Beckmann, C. Bonny

Published in: Diabetologia | Issue 9/2009

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Abstract

Aims/hypothesis

In insulin-secreting cells, activation of the c-Jun NH2-terminal kinase (JNK) pathway triggers apoptosis. Whereas JNK1 and JNK2 are ubiquitously produced, JNK3 has been described exclusively in neurons. This report aims to characterise the expression and role in apoptosis of the three JNK isoforms in insulin-secreting cells exposed to cytokines.

Methods

Sections of human and mouse pancreases were used for immunohistochemistry studies with isoform-specific anti-JNK antibodies. Human, pig, mouse and rat pancreatic islets were isolated by enzymatic digestion and RNA or protein extracts were prepared. RNA and protein levels were determined by quantitative RT-PCR and western blotting respectively, using JNK-isoform-specific primers and isoform-specific antibodies; activities of the three JNK isoforms were determined by kinase assays following quantitative immunoprecipitation/depletion of JNK3. JNK silencing was performed with small interfering RNAs and apoptotic rates were determined in INS-1E cells by scoring cells displaying pycnotic nuclei.

Results

JNK3 and JNK2 mRNAs are the predominant isoforms expressed in human pancreatic islets. JNK3 is nuclear while JNK2 is also cytoplasmic. In INS-1E cells, JNK3 knockdown increases c-Jun levels and caspase-3 cleavage and sensitises cells to cytokine-induced apoptosis; in contrast, JNK1 or JNK2 knockdown is protective.

Conclusions/interpretation

In insulin-secreting cells, JNK3 plays an active role in preserving pancreatic beta cell mass from cytokine attacks. The specific localisation of JNK3 in the nucleus, its recruitment by cytokines, and its effects on key transcription factors such as c-Jun, indicate that JNK3 is certainly an important player in the transcriptional control of genes expressed in insulin-secreting cells.
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Metadata
Title
JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis
Authors
S. Abdelli
J. Puyal
C. Bielmann
V. Buchillier
A. Abderrahmani
P. G. H. Clarke
J. S. Beckmann
C. Bonny
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1431-7

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