Caspase-2 and JNK Activated by Saturated Fatty Acids are Not Involved in Apoptosis Induction but Modulate ER Stress in Human Pancreatic �-cells

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.

Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin

“…We are proceeding to describe that endogenous production of stearic acid was increased while total MUFA (oleic acid and palmitoleic acid) was decreased in the pancreas of diabetic rats. These findings align with other studies showing that stearic acid induced endoplasmic reticulum stress of pancreatic β-cells [60]. In fact, a substantial increase in stearic acid content of pancreatic islets incubated in the presence of glucose had been previously reported [61].…”

Differentially expressed proteins in human MCF-7 breast cancer cells sensitive and resistant to paclitaxel

“…The cells were cultured in a medium based on the RPMI 1640 (Sigma-Aldrich, St. Louis, MO, USA) containing phenol red, extra L-glutamine (300 μg/ml), sodium pyruvate (110 μg/ml), HEPES (15 mM), penicillin (100 U/ml) and streptomycin (100 μg/ml), as previously described [29,30]. The medium was also supplemented with 10% heat-inactivated fetal bovine serum (Biochrom AG, Berlin, Germany).…”

Antagonism Between Saturated and Unsaturated Fatty Acids in ROS Mediated Lipotoxicity in Rat Insulin-Producing Cells

“…Hyperlipidaemia, in turn, is typically associated with elevated non-esterified fatty acid (NEFA) plasma concentrations, which are supposed to contribute to insulin resistance, impaired insulin secretion due to a progressive decline in pancreatic β-cell function and mass, a phenomenon called lipotoxicity [5][6][7]. In vitro studies have shown that long-chain saturated NEFAs can induce apoptosis [8][9][10][11]. This has been considered, at least in part, to be mediated by the induction of the unfolded protein response (UPR) [12].…”