| OBJECTIVE: To explore Protective Effect and Possible Mechanism of GLP-1 analogues on the endoplasmic reticulum stress pathway of apoptosis in Murine Pancreaticβ-cellsMETHODS: Mouse insulinoma(MIN6) cells was administered with t-BHP which were cultured in vitro. Choosing medicine with different concentrations(0-400μmol/L)and time periods(0.5-8h)to establish the cells apoptosis model. Then cells were pretreated with exendin-4(100nmol/L)prior to exposure to t-BHP. The percentage of cell viability was determined through MTT assay. and CCK-8. The percentage of apoptosis was determined through fluorsecence microsopic analysis after hochest/PI staining and flow cytometric assay after Annexin-Ⅴ-FITC-PI staining. The content of caspase-3 was measured by the caspase-3 activity assay kit. The expression of Endoplasmic reticulum stress-related molecules and the apoptosis signal pathway JNK,P-JNK,c-Jun,P-c-Jun,Caspase-3 were detected by western-blotRESULTS: The percentage of MIN6 cell viability reduced with the concentration of t-BHP increasing. The caspase-3 was actived after exposured of t-BHP up to 50μmol/L for 1 hour or 25μmol/L for continuing 3 hours. The endoplasmic reticulum stress transmembrane protein molecule IRE1 and apoptosis-related signaling molecules JNK were actived after exposured of t-BHP. After pretreated with exendin-4, the percentage of MIN6 cell viability was greatly improved. Furthermore,the present study showed that exendin-4 patently inhibited the activie of IRE1,JNK,c-Jun and caspase-3. CONCLUSION: The study demonstrates that the percentage of MIN6 cell viability was reduced in a dose-dependent manner. Continuous exposuring of t-BHP induced oxidative damage in MIN6 cells to endoplasmic reticulum stress and apoptosis .Our results also suggest that exendin-4 protects against endoplasmic reticulum stress-indured apoptosis associated with improving ERS and the apoptosis-related signaling.
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