Li Wu1, XiaoYing Liu2, LinXi Wang1, YanPing Wang1, LiJing Wang1, BinBin Guan1, Zhou Chen3, LiBin Liu4,5. 1. Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. 2. Department of Geriatrics, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. 3. College of Pharmacy, Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. kellandchen1007@hotmail.com. 4. Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. libin.liu@fjmu.edu.cn. 5. Institute of the Geriatric Health Sciences, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. libin.liu@fjmu.edu.cn.
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.
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.
Authors: Hisko Oeseburg; Rudolf A de Boer; Hendrik Buikema; Pim van der Harst; Wiek H van Gilst; Herman H W Silljé Journal: Arterioscler Thromb Vasc Biol Date: 2010-05-06 Impact factor: 8.311
Authors: Mete Civelek; Elisabetta Manduchi; Rebecca J Riley; Christian J Stoeckert; Peter F Davies Journal: Circ Res Date: 2009-08-06 Impact factor: 17.367