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Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway

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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

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Acknowledgements

This work was supported by grants from the Science and Technology Key Funding of Fujian Province of China (No. 2013Y0041), the Nursery Funding of Fujian Medical University (No. 2014MP031), the Youth Funding of Fujian Province Health Department (No. 2014-1-43) and the National and Fujian Province’s Key Clinical Specialty Discipline Construction Programs.

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Correspondence to Zhou Chen or LiBin Liu.

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Wu, L., Liu, X., Wang, L. et al. Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway. Endocrine 55, 764–772 (2017). https://doi.org/10.1007/s12020-016-1190-4

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  • DOI: https://doi.org/10.1007/s12020-016-1190-4

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