Exendin-4 protected murine MIN6 pancreatic beta-cells from oxidative stress-induced apoptosis via down-regulation of NF-kappaB-iNOS-NO pathway.
- Author:
Li-bin LIU
1
;
Yan-ping WANG
;
Xiao-dong PAN
;
Su-yuan JIANG
;
Zhou CHEN
Author Information
1. Fujian Institute of Endocrinology, the Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, China. libinliu@medmail.com.cn
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
drug effects;
Down-Regulation;
Glucagon-Like Peptide-1 Receptor;
Hypoglycemic Agents;
pharmacology;
Incretins;
agonists;
Insulin-Secreting Cells;
cytology;
metabolism;
Lizards;
Mice;
Nitric Oxide;
metabolism;
Nitric Oxide Synthase Type II;
metabolism;
Oxidative Stress;
drug effects;
Peptides;
pharmacology;
Receptors, Glucagon;
agonists;
Signal Transduction;
Transcription Factor RelA;
metabolism;
Venoms;
pharmacology;
tert-Butylhydroperoxide;
pharmacology
- From:
Acta Pharmaceutica Sinica
2008;43(7):690-694
- CountryChina
- Language:Chinese
-
Abstract:
To explore the effect of glucagon-like peptide-1 receptor agonist--Exendin-4 (Ex-4) on murine MIN6 pancreatic beta-cells apoptosis induced by oxidative stress, the morphological changes of cell damage were evaluated by epifluorescence microscopy after staining with AO-EB. The percentage of cell apoptosis was determined by flow cytometric assay after Annexin-V-FITC-PI staining. Nitric oxide level was measured by Griess reagent assay. Inducible nitric oxide synthase (iNOS) protein and NF-kappaBp65 fragment were detected by Western blotting. Ex-4 inhibited the increase of nitrite level and percentage of apoptosis induced by t-BHP in MIN6 cells. Furthermore, Ex-4 partly reduced the expression of iNOS protein and the ratio of NF-kappaBp65 protein in nucleus:cytosol induced by t-BHP. These results suggest that Ex4 protects MIN6 pancreatic kappa-cells from oxidative stress-induced apoptosis via down-regulation of NF-kappaB-iNOS-nitric oxide pathway.
