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Title: Caspase-2 and JNK Activated by Saturated Fatty Acids are Not Involved in Apoptosis Induction but Modulate ER Stress in Human Pancreatic β-cells
Authors: James, Roger F. L.
Němcová-Fürstová, V.
Balušíková, K.
Šrámek, J.
Kovář, J.
First Published: 22-Aug-2013
Publisher: Karger
Citation: Cellular Physiology and Biochemistry, 2013, 31, pp. 277-289
Abstract: Background: Fatty acid-induced apoptosis and ER stress of pancreatic β-cells contribute to the development of type 2 diabetes, however, the molecular mechanisms involved are unclear. Aims: In this study we have tested the role of caspase-2 and suggested ER stress mediator JNK in saturated fatty acid-induced apoptosis of the human pancreatic β-cells NES2Y. Results: We found that stearic acid at apoptosis-inducing concentration activated ER stress signaling pathways, i.e. IRE1α, PERK and ATF6 pathways, in NES2Y cells. During stearic acid-induced apoptosis, JNK inhibition did not decrease the rate of apoptosis nor the activation of caspase-8, -9, -7 and -2 and PARP cleavage. In addition, inhibition of JNK activity did not affect CHOP expression although it did decrease the induction of BiP expression after stearic acid treatment. Caspase-2 silencing had no effect on PARP as well as caspase-8, -9 and -7 cleavage and the induction of CHOP expression, however, it also decreased the induction of BiP expression. Surprisingly, caspase-2 silencing was accompanied by increased phosphorylation of c-Jun. Conclusions: We have demonstrated that caspase-2 as well as JNK are not key players in apoptosis induction by saturated fatty acids in human pancreatic β-cells NES2Y. However, they appear to be involved in the modulation of saturated fatty acid-induced ER stress signaling, probably by a mechanism independent of c-Jun phosphorylation.
DOI Link: 10.1159/000343367
ISSN: 1421-9778
eISSN: 1421-9778
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2013. This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (, applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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