title: Exendin-4 protects HUVECs from t-BHP-induced apoptosis via PI3K/Akt-Bcl-2-caspase-3 signaling.
abstract: OBJECTIVE
  Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. In this study, we explored the effect and mechanism of exendin-4 on tert-butyl hydroperoxide (t-BHP)-induced apoptosis in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  HUVECs were treated with 100 µmol/L t-BHP for 4 h, following pretreatment with 2.5-25 nmol/L exendin-4. Cell viability was determined using an dimethyl thiazolyl diphenyl tetrazolium salt (MTT) assay. The percentage of apoptotic cells was determined by fluorescence microscopy after Hoechst/PI staining. Expression of cysteine-aspartic acid protease-3(caspase-3), beta-cell lymphoma 2(Bcl-2), protein kinase B(AKT), and phosphorylated AKT was detected by western blotting.
  
  
  RESULTS
  Exendin-4 reduced the percentage of cells undergoing apoptosis when HUVECs were exposed to t-BHP. Exendin-4 downregulated caspase-3 activity and increased Bcl-2 protein levels in t-BHP-treated HUVECs. These exendin-4-mediated effects were blocked in the presence of an inhibitor of phosphoinositide-3 kinase (PI3K). Exendin-4 reversed t-BHP-mediated inhibition of Akt phosphorylation, which was abrogated by the PI3K inhibitor, wortmannin.
  
  
  CONCLUSIONS
  Our findings suggest that exendin-4 reduces t-BHP-induced apoptosis of HUVECs. Additionally, PI3K/Akt-Bcl-2-caspase-3 signaling is involved in the exendin-4-mediated modulation of HUVECs.
authors.affiliation: a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , Fujian , China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Wang
authors.affiliation: b Department of Nephrology , The Xianyang Central Hospital , Shanxi , China.|c Xi'an Jiaotong University Health Science Center , Shanxi , China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , Fujian , China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , Fujian , China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , Fujian , China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Liu
authors.affiliation: a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , Fujian , China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: d Department of Pharmacy , Fujian Medical University , Fuzhou , Fujian , People's Republic of China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , Fujian , China.|e Elderly Health Institute , Fujian Medical University , Fuzhou , Fujian , China.
authors.forename: Libin
authors.initials: L
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014471:Umbilical Veins; D014688:Venoms / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D020122:tert-Butylhydroperoxide; D000077270:Exenatide
keywords: Apoptosis; Bcl-2; HUVECs; glucagon-like peptide-1; phosphoinositide-3 kinase; t-BHP