Role of p38 MAPK pathway in apoptosis induction by saturated fatty acid in human pancreatic β-cells

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Abstract


Background. Pancreatic β-cells failure and apoptosis in response to chronically elevated concentrations of saturated fatty acids in blood was considered as one of the main causes of type 2 diabetes mellitus development. Although precise molecular mechanisms of this process are still unclear, there are some indications that the p38 MAPK signaling pathway could be involved.

Aim, materials and methods. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in human pancreatic β-cells NES2Y. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested.

Results. We have found that saturated SA at apoptosis-inducing concentration (1 mM) activated the p38 MAPK signaling pathway MKK3/6→p38 MAPK→MAPKAPK-2 and inhibited the ERK signaling pathway c-Raf→MEK1/2→ERK1/2. The inhibition of p38 MAPK expression by siRNA silencing had no significant effect on cell viability or the level of phosphorylated ERK pathway members after SA administration. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced no significant influence on cell viability or ERK pathway activation after SA exposure. The activation of p38 MAPK by the specific activator anisomycin led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, -8, and -9 activation) and in inhibition of ERK pathway members.

Conclusions. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic β-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SA-induced apoptosis.


Jan Šrámek

Author for correspondence.
jan.sramek@lf3.cuni.cz
Charles University in Prague
Czech Republic

Assistant of Department of Cell and Molecular Biology, Third Faculty of Medicine

Vlasta Němcová-Fürstová

jan.sramek@lf3.cuni.cz
Charles University in Prague
Czech Republic

Kamila Balušíková

jan.sramek@lf3.cuni.cz
Charles University in Prague
Czech Republic

Petr Daniel

jan.sramek@lf3.cuni.cz
Charles University in Prague
Czech Republic

Michael Jelínek

jan.sramek@lf3.cuni.cz
Charles University in Prague
Czech Republic

Jan Kovář

jan.sramek@lf3.cuni.cz
Charles University in Prague
Czech Republic

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Copyright (c) 2016 Šrámek J., Němcová-Fürstová V., Balušíková K., Daniel P., Jelínek M., Kovář J.

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