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Exendin-4 protects HUVECs from t-BHP-induced apoptosis via PI3K/Akt-Bcl-2-caspase-3 signaling.
- Source :
-
Endocrine research [Endocr Res] 2016 Aug; Vol. 41 (3), pp. 229-35. Date of Electronic Publication: 2016 Mar 30. - Publication Year :
- 2016
-
Abstract
- 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).<br />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.<br />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.<br />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.
Details
- Language :
- English
- ISSN :
- 1532-4206
- Volume :
- 41
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Endocrine research
- Publication Type :
- Academic Journal
- Accession number :
- 27030608
- Full Text :
- https://doi.org/10.3109/07435800.2015.1110162