Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 31, Issue 2-3, Pages 277-289Publisher
KARGER
DOI: 10.1159/000343367
Keywords
Caspase-2; JNK; Saturated fatty acids; Apoptosis; Endoplasmic reticulum stress; beta-cells
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Funding
- Third Faculty of Medicine, Charles University in Prague, Ministry of Education, Youth and Sports of the Czech Republic [MSM0021620814]
- Charles University in Prague, Czech Republic [SVV-2010-260704, SVV-2011-262706, UNCE 204015, PRVOUK P31]
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Background: Fatty acid-induced apoptosis and ER stress of pancreatic beta-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 beta-cells NES2Y. Results: We found that stearic acid at apoptosis-inducing concentration activated ER stress signaling pathways, i.e. IRE1 alpha, 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 beta-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. Copyright (C) 2013 S. Karger AG, Basel
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