Exendin-4 protects HUVECs from t-BHP-induced apoptosis via PI3K/Akt-Bcl-2-caspase-3 signaling.
AIMS
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.


CONCLUSION
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.
['Wang|Linxi|L|', 'Tang|Li|L|', 'Wang|Yanping|Y|', 'Wang|Lijing|L|', 'Liu|Xiaoying|X|', 'Liu|Xiaohong|X|', 'Chen|Zhou|Z|', 'Liu|Libin|L|']
D017209:Apoptosis D002478:Cells, Cultured D042783:Endothelial Cells D000077270:Exenatide D006801:Humans D007004:Hypoglycemic Agents D010455:Peptides D015398:Signal Transduction D014471:Umbilical Veins D014688:Venoms D020122:tert-Butylhydroperoxide
HUVECs Apoptosis glucagon-like peptide-1 t-BHP Bcl-2 phosphoinositide-3 kinase