Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway
| Autor: | Zhou Chen, Xiao-Ying Liu, Yanping Wang, Bin-Bin Guan, Linxi Wang, Lijing Wang, Libin Liu, Li Wu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty Cell Survival MAP Kinase Signaling System medicine.drug_class Endocrinology Diabetes and Metabolism Apoptosis Caspase 3 Protein Serine-Threonine Kinases 030204 cardiovascular system & hematology Incretins Umbilical vein 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Internal medicine Endoribonucleases Cyclic AMP Human Umbilical Vein Endothelial Cells medicine Humans Phosphorylation Receptor Venoms Chemistry Vascular disease Tunicamycin Endoplasmic reticulum medicine.disease Cell biology 030104 developmental biology Exenatide Peptides |
| Zdroj: | Endocrine. 55:764-772 |
| ISSN: | 1559-0100 1355-008X |
| DOI: | 10.1007/s12020-016-1190-4 |
| Popis: | The abnormal increase of apoptosis of endothelial cells induced by endoplasmic reticulum stress is a significant factor for vascular disease, especially for atherosclerosis. Protecting endothelial cells from endoplasmic reticulum stress is a crucial strategies to combate these diseases. The goal of this study was to explore the effect of Exendin-4, a glucagon-like peptide-1 receptor agonist, on tunicamycin-induced apoptosis in human umbilical vein endothelial cells.All studies were performed in primary human umbilical vein endothelial cells treated with tunicamycin with or without Exendin-4 pretreatment. Markers of cell viability and apoptosis were assessed in all cells, as well as the protein expression levels of IRE1α (inositol requiring enzyme-1а), p-IRE1α, JNK (c-Jun N-terminal kinase), p-JNK, and caspase-3.Following tunicamycin administration, human umbilical vein endothelial cells viability was gradually reduced in a dose-dependent manner, and fluorescence microscopy confirmed that tunicamycin was inducing human umbilical vein endothelial cells apoptosis. This apoptotic effect was attenuated by Exendin-4 pretreatment. Similarly, the ratio of p-IRE1α/IRE1α, p-JNK/JNK and active caspase-3/procaspase-3 were increased by tunicamycin (10 μg/ml); an effect that was counteracted by Exendin-4. The effect of exendin-4 was similar to that of the anti-endoplasmic reticulum stress agent, tauroursodeoxycholic acid (TUDCA).This study demonstrates that Exendin-4 can protect human umbilical vein endothelial cells from tunicamycin-induced apoptosis. Furthermore, our data suggests that the mechanism for this effect is mediated by inhibiting the IRE1α/JNK/caspase-3 pathway. |
| Databáze: | OpenAIRE |
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