Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling
Objectives. This study aimed to explore the effect of exendin-4 on t-BHP-induced apoptosis in pancreatic β cells and the mechanism of action. Methods. Murine MIN6 pancreatic β cells were treated with exendin-4 in the presence or absence of tert-butyl hydroperoxide (t-BHP). Cell survival was assessed...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2012/549081 |
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| author | Wen-Jia Chen Lin-Xi Wang Yan-Ping Wang Zhou Chen Xiao-Ying Liu Xiao-Hong Liu Li-Bin Liu |
| author_facet | Wen-Jia Chen Lin-Xi Wang Yan-Ping Wang Zhou Chen Xiao-Ying Liu Xiao-Hong Liu Li-Bin Liu |
| author_sort | Wen-Jia Chen |
| collection | DOAJ |
| description | Objectives. This study aimed to explore the effect of exendin-4 on t-BHP-induced apoptosis in pancreatic β cells and the mechanism of action. Methods. Murine MIN6 pancreatic β cells were treated with exendin-4 in the presence or absence of tert-butyl hydroperoxide (t-BHP). Cell survival was assessed by MTT staining. The percentage of apoptotic cells was determined by fluorescence microscopy analysis after Hoechst/PI staining and flow cytometric assay after Annexin V-FITC/PI staining. The activity of caspase-3 was determined using a caspase-3 activity kit. Expression of P-IRE1α, IRE1α, C-Jun N-terminal kinase (JNK), P-JNK, C-JUN, and P-C-JUN was detected by western blotting. Results. Exendin-4 was found to inhibit t-BHP-induced apoptosis in pancreatic β-cells by downregulating caspase-3 activity. Exendin-4 also inhibited the endoplasmic reticulum transmembrane protein IRE1, the apoptosis-related signaling molecule JNK, and c-Jun activation. Conclusions. Our findings suggest that exendin-4 ultimately reduces t-BHP-induced β-cell apoptosis. IRE1-JNK-c-Jun signaling is involved in the exendin-4-mediated modulation of β-cell apoptosis. |
| format | Article |
| id | doaj-art-f7d5d60613234f8caa05f8531d151d7d |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-f7d5d60613234f8caa05f8531d151d7d2025-02-03T06:05:20ZengWileyInternational Journal of Endocrinology1687-83371687-83452012-01-01201210.1155/2012/549081549081Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 SignalingWen-Jia Chen0Lin-Xi Wang1Yan-Ping Wang2Zhou Chen3Xiao-Ying Liu4Xiao-Hong Liu5Li-Bin Liu6Department of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaDepartment of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaDepartment of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaDepartment of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaDepartment of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaDepartment of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaDepartment of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, ChinaObjectives. This study aimed to explore the effect of exendin-4 on t-BHP-induced apoptosis in pancreatic β cells and the mechanism of action. Methods. Murine MIN6 pancreatic β cells were treated with exendin-4 in the presence or absence of tert-butyl hydroperoxide (t-BHP). Cell survival was assessed by MTT staining. The percentage of apoptotic cells was determined by fluorescence microscopy analysis after Hoechst/PI staining and flow cytometric assay after Annexin V-FITC/PI staining. The activity of caspase-3 was determined using a caspase-3 activity kit. Expression of P-IRE1α, IRE1α, C-Jun N-terminal kinase (JNK), P-JNK, C-JUN, and P-C-JUN was detected by western blotting. Results. Exendin-4 was found to inhibit t-BHP-induced apoptosis in pancreatic β-cells by downregulating caspase-3 activity. Exendin-4 also inhibited the endoplasmic reticulum transmembrane protein IRE1, the apoptosis-related signaling molecule JNK, and c-Jun activation. Conclusions. Our findings suggest that exendin-4 ultimately reduces t-BHP-induced β-cell apoptosis. IRE1-JNK-c-Jun signaling is involved in the exendin-4-mediated modulation of β-cell apoptosis.http://dx.doi.org/10.1155/2012/549081 |
| spellingShingle | Wen-Jia Chen Lin-Xi Wang Yan-Ping Wang Zhou Chen Xiao-Ying Liu Xiao-Hong Liu Li-Bin Liu Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling International Journal of Endocrinology |
| title | Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling |
| title_full | Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling |
| title_fullStr | Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling |
| title_full_unstemmed | Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling |
| title_short | Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling |
| title_sort | exendin 4 protects min6 cells from t bhp induced apoptosis via ire1 jnk caspase 3 signaling |
| url | http://dx.doi.org/10.1155/2012/549081 |
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