AIMS: In this study we have tested the effect of unsaturated fatty acids on the proapoptotic effects of saturated fatty acids in the human pancreatic β-cells NES2Y. RESULTS: We found that unsaturated palmitoleic and oleic acid at a concentration of 0.2 mM and higher are able to completely inhibit the proapoptotic effect of their counterpart saturated palmitic and stearic acid at a concentration of 1 mM. Apoptosis induced by stearic acid was associated with significant activation of caspase-6, -7, -9, -2 and -8, but not with significant activation of caspase-3. The activation of caspases was blocked by coincubation with oleic acid. Stearic acid treatment was not associated with a significant change in mitochondrial membrane potential, reactive oxygen species level and with cytochrome c release from mitochondria. Furthermore, stearic acid treatment was not associated with changes in p21(WAF1/CIP1), PIDD, Fas receptor and Fas ligand expression. However, we detected endoplasmic reticulum (ER) stress markers, i. e. a significant upregulation of BiP and CHOP expression as well as XBP1 mRNA splicing. These changes were inhibited by coincubation with oleic acid. CONCLUSION: Presented data indicate that oleic acid inhibits apoptosis induction by stearic acid in NES2Y cells upstream of caspase activation and ER stress induction. It does not involve an interference with the mitochondrial pathway of apoptosis induction, with p53 activation and PIDD expression as well as with Fas receptor and Fas ligand expression.

Department of Cell and Molecular Biology and Center for Research of Diabetes Metabolism and Nutrition 3rd Faculty of Medicine Charles University Ruská 87 Prague Czech Republic

Citace poskytuje Crossref.org

Calcium channel blockers do not protect against saturated fatty acid-induced ER stress and apoptosis in human pancreatic β-cells

Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells

Markers of acute toxicity of DDT exposure in pancreatic beta-cells determined by a proteomic approach

Hypoxia Modulates Effects of Fatty Acids on NES2Y Human Pancreatic β-cells

Effect of Saturated Stearic Acid on MAP Kinase and ER Stress Signaling Pathways during Apoptosis Induction in Human Pancreatic β-Cells Is Inhibited by Unsaturated Oleic Acid

Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells

p38 MAPK Is Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Acid in Human Pancreatic β-Cells

Mitochondrial function in skeletal muscle of patients with protracted critical illness and ICU-acquired weakness