Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy
Background Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decre...
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Korean Society of Anesthesiologists
2024-12-01
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| Series: | Korean Journal of Anesthesiology |
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| Online Access: | http://ekja.org/upload/pdf/kja-24457.pdf |
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| author | Jin Ha Park Ju Eun Oh Namo Kim Young-Lan Kwak |
| author_facet | Jin Ha Park Ju Eun Oh Namo Kim Young-Lan Kwak |
| author_sort | Jin Ha Park |
| collection | DOAJ |
| description | Background Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic β-cell damage by regulating autophagy under hypoxia. Methods INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine. Results Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1. Conclusions Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice. |
| format | Article |
| id | doaj-art-473e7d3d04f14fafb66f1dec997fcee4 |
| institution | Kabale University |
| issn | 2005-6419 2005-7563 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Korean Society of Anesthesiologists |
| record_format | Article |
| series | Korean Journal of Anesthesiology |
| spelling | doaj-art-473e7d3d04f14fafb66f1dec997fcee42024-12-09T08:30:35ZengKorean Society of AnesthesiologistsKorean Journal of Anesthesiology2005-64192005-75632024-12-0177662363410.4097/kja.244579010Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagyJin Ha Park0Ju Eun Oh1Namo Kim2Young-Lan Kwak3 Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, KoreaBackground Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic β-cell damage by regulating autophagy under hypoxia. Methods INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine. Results Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1. Conclusions Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice.http://ekja.org/upload/pdf/kja-24457.pdfautophagybeta cellscell injurycobalt chloridedexmedetomidinehypoxiapancreasrat |
| spellingShingle | Jin Ha Park Ju Eun Oh Namo Kim Young-Lan Kwak Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy Korean Journal of Anesthesiology autophagy beta cells cell injury cobalt chloride dexmedetomidine hypoxia pancreas rat |
| title | Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy |
| title_full | Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy |
| title_fullStr | Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy |
| title_full_unstemmed | Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy |
| title_short | Dexmedetomidine alleviates CoCl-induced hypoxic cellular damage in INS-1 cells by regulating autophagy |
| title_sort | dexmedetomidine alleviates cocl induced hypoxic cellular damage in ins 1 cells by regulating autophagy |
| topic | autophagy beta cells cell injury cobalt chloride dexmedetomidine hypoxia pancreas rat |
| url | http://ekja.org/upload/pdf/kja-24457.pdf |
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