title: Exendin-4 protects HUVECs from tunicamycin-induced apoptosis via inhibiting the IRE1a/JNK/caspase-3 pathway.
abstract: OBJECTIVE
  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.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Geriatrics, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China.
authors.forename: XiaoYing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China.
authors.forename: LinXi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China.
authors.forename: YanPing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China.
authors.forename: LiJing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Fujian Medical University Union Hospital; Fujian Institute of Endocrinology, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China.
authors.forename: BinBin
authors.initials: B
authors.lastname: Guan
authors.affiliation: College of Pharmacy, Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. kellandchen1007@hotmail.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 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.|Institute of the Geriatric Health Sciences, 29 Xinquan Road, Fuzhou, Fujian, 350001, People's Republic of China. libin.liu@fjmu.edu.cn.
authors.forename: LiBin
authors.initials: L
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism*; D000077270:Exenatide; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D054795:Incretins; D010455:Peptides; D014688:Venoms; D014415:Tunicamycin; D000077270:Exenatide; D000242:Cyclic AMP; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D053148:Caspase 3
keywords: Apoptosis; Endoplasmic reticulum stress; Exendin-4; HUVECs; Tunicamycin