title: p38 MAPK Is Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Acid in Human Pancreatic β-Cells.
abstract: Saturated stearic acid (SA) induces apoptosis in the human pancreatic β-cells NES2Y. However, the molecular mechanisms involved are unclear. We showed that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway in these cells. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in NES2Y cells. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested. The inhibition of p38 MAPK expression by siRNA silencing resulted in a decrease in MAPKAPK-2 activation after SA application, but it had no significant effect on cell viability or the level of phosphorylated ERK pathway members. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in inhibition of MAPKAPK-2 activation and noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced an increase in MAPKAPK-2 activation after SA exposure but no significant influence on cell viability or ERK pathway activation. The activation of p38 MAPK by the specific activator anisomycin resulted in significant activation of MAPKAPK-2. Concerning the effect on cell viability, application of the activator 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. 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.
authors: Division of Cell and Molecular Biology &amp; Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague 110 00, Czech Republic. jan.sramek@seznam.cz.
authors: Jan
authors: J
authors: Šrámek
authors: Division of Cell and Molecular Biology &amp; Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague 110 00, Czech Republic. vlasta.furstova@tiscali.cz.
authors: Vlasta
authors: V
authors: Němcová-Fürstová
authors: Division of Cell and Molecular Biology &amp; Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague 110 00, Czech Republic. kamila.balusikova@lf3.cuni.cz.
authors: Kamila
authors: K
authors: Balušíková
authors: Division of Cell and Molecular Biology &amp; Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague 110 00, Czech Republic. petr85daniel@gmail.com.
authors: Petr
authors: P
authors: Daniel
authors: Division of Cell and Molecular Biology &amp; Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague 110 00, Czech Republic. michael.j@email.cz.
authors: Michael
authors: M
authors: Jelínek
authors: Department of Infection, Immunity and Inflammation, Maurice Shock Medical Sciences Building, University of Leicester, University Road, Leicester LE1 9HN, UK. rj1@leicester.ac.uk.
authors: Roger F
authors: RF
authors: James
authors: Division of Cell and Molecular Biology &amp; Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague 110 00, Czech Republic. jan.kovar@lf3.cuni.cz.
authors: Jan
authors: J
authors: Kovář
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D047428:Protein Kinase Inhibitors; D013229:Stearic Acids; C031183:stearic acid; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ERK; NES2Y; apoptosis; fatty acids; p38 MAPK; pancreatic β-cells