[Exendin-4 protected murine MIN6 pancreatic beta-cells from oxidative stress-induced apoptosis via down-regulation of NF-kappaB-iNOS-NO pathway].
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.
Liu
Li-bin
LB
Fujian Institute of Endocrinology, the Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, China. libinliu@medmail.com.cn
Wang
Yan-ping
YP
Pan
Xiao-dong
XD
Jiang
Su-yuan
SY
Chen
Zhou
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015536:Down-Regulation; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054795:Incretins / Q000819:agonists; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008116:Lizards; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000819:agonists; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D018027:Receptors, Glucagon; D051996:Transcription Factor RelA; D014688:Venoms; D009569:Nitric Oxide; D020122:tert-Butylhydroperoxide; D000077270:Exenatide; D052247:Nitric Oxide Synthase Type II