Inhibitory effect of unsaturated fatty acids on saturated fatty acid-induced apoptosis in human pancreatic β-cells: activation of caspases and ER stress induction
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21691070
DOI
10.1159/000329954
PII: 000329954
Knihovny.cz E-resources
- MeSH
- Enzyme Activation MeSH
- Apoptosis drug effects MeSH
- Insulin-Secreting Cells cytology drug effects metabolism MeSH
- Endoplasmic Reticulum Chaperone BiP MeSH
- Cytochromes c analysis MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- Endoplasmic Reticulum drug effects metabolism MeSH
- Gene Expression drug effects MeSH
- Stress, Physiological MeSH
- Caspases metabolism MeSH
- Oleic Acid pharmacology MeSH
- Fatty Acids, Monounsaturated pharmacology MeSH
- Stearic Acids pharmacology MeSH
- Humans MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- RNA, Messenger MeSH
- Mitochondria drug effects metabolism MeSH
- Heat-Shock Proteins genetics metabolism MeSH
- Flow Cytometry MeSH
- RNA Splicing MeSH
- Cell Line, Transformed MeSH
- Transcription Factor CHOP genetics metabolism MeSH
- Regulatory Factor X Transcription Factors MeSH
- Transcription Factors genetics metabolism MeSH
- Up-Regulation drug effects MeSH
- X-Box Binding Protein 1 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Endoplasmic Reticulum Chaperone BiP MeSH
- Cytochromes c MeSH
- DDIT3 protein, human MeSH Browser
- DNA-Binding Proteins MeSH
- Caspases MeSH
- Oleic Acid MeSH
- Fatty Acids, Monounsaturated MeSH
- Stearic Acids MeSH
- RNA, Messenger MeSH
- palmitoleic acid MeSH Browser
- Heat-Shock Proteins MeSH
- stearic acid MeSH Browser
- Transcription Factor CHOP MeSH
- Regulatory Factor X Transcription Factors MeSH
- Transcription Factors MeSH
- XBP1 protein, human MeSH Browser
- X-Box Binding Protein 1 MeSH
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.
References provided by Crossref.org
Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells
Hypoxia Modulates Effects of Fatty Acids on NES2Y Human Pancreatic β-cells
Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells
