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Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis

The purpose of the present study is to define the role of sevoflurane (SEV) in hepatic ischemia-reperfusion (I/R) injury as well as its underlying mechanism. Initially, hepatic I/R animal models and I/R hepatocyte models were established in C57BL/6 mice and normal mouse hepatocytes (BNL CL.2) after...

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Autores principales: Wang, Yi-Liang, Zhang, Ying, Cai, Da-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904859/
https://www.ncbi.nlm.nih.gov/pubmed/35260558
http://dx.doi.org/10.1038/s41420-021-00784-7
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author Wang, Yi-Liang
Zhang, Ying
Cai, Da-Sheng
author_facet Wang, Yi-Liang
Zhang, Ying
Cai, Da-Sheng
author_sort Wang, Yi-Liang
collection PubMed
description The purpose of the present study is to define the role of sevoflurane (SEV) in hepatic ischemia-reperfusion (I/R) injury as well as its underlying mechanism. Initially, hepatic I/R animal models and I/R hepatocyte models were established in C57BL/6 mice and normal mouse hepatocytes (BNL CL.2) after SEV preconditioning, respectively, followed by detection of microRNA-124-3p (miR-124-3p), TRAF3, and CREB expression by RT-qPCR and Western blot analysis. In addition, miR-124-3p, TRAF3 and CREB expression in hepatocytes was altered to identify their roles in modulating the levels of glutathione transferase (GST), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inflammation-related factors and hepatocyte apoptosis by ELISA and flow cytometry respectively. The effects of SEV on the miR-124-3p/TRAF3/CREB axis were also verified in vitro and in vivo. IP assay was performed to verify the effect of TRAF3 on CREB ubiquitination in BNL CL.2 cells, and the cycloheximide (CHX) intervention experiment to detect the stability of CREB protein. SEV augmented the miR-124-3p expression in I/R animal and cell models. Moreover, SEV was observed to suppress I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation. Overexpression of miR-124-3p resulted in alleviation of hepatic I/R injury, which was countered by TRAF3 overexpression. miR-124-3p targeted TRAF3, while TRAF3 promoted CREB ubiquitination and reduced protein stability of CREB. SEV could impede I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation via mediation of the miR-124-3p/TRAF3/CREB axis in vitro and in vivo. Collectively, SEV may upregulate miR-124-3p to inhibit TRAF3 expression, thereby reducing the ubiquitination and degradation of CREB, alleviating hepatic I/R injury.
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spelling pubmed-89048592022-03-23 Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis Wang, Yi-Liang Zhang, Ying Cai, Da-Sheng Cell Death Discov Article The purpose of the present study is to define the role of sevoflurane (SEV) in hepatic ischemia-reperfusion (I/R) injury as well as its underlying mechanism. Initially, hepatic I/R animal models and I/R hepatocyte models were established in C57BL/6 mice and normal mouse hepatocytes (BNL CL.2) after SEV preconditioning, respectively, followed by detection of microRNA-124-3p (miR-124-3p), TRAF3, and CREB expression by RT-qPCR and Western blot analysis. In addition, miR-124-3p, TRAF3 and CREB expression in hepatocytes was altered to identify their roles in modulating the levels of glutathione transferase (GST), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inflammation-related factors and hepatocyte apoptosis by ELISA and flow cytometry respectively. The effects of SEV on the miR-124-3p/TRAF3/CREB axis were also verified in vitro and in vivo. IP assay was performed to verify the effect of TRAF3 on CREB ubiquitination in BNL CL.2 cells, and the cycloheximide (CHX) intervention experiment to detect the stability of CREB protein. SEV augmented the miR-124-3p expression in I/R animal and cell models. Moreover, SEV was observed to suppress I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation. Overexpression of miR-124-3p resulted in alleviation of hepatic I/R injury, which was countered by TRAF3 overexpression. miR-124-3p targeted TRAF3, while TRAF3 promoted CREB ubiquitination and reduced protein stability of CREB. SEV could impede I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation via mediation of the miR-124-3p/TRAF3/CREB axis in vitro and in vivo. Collectively, SEV may upregulate miR-124-3p to inhibit TRAF3 expression, thereby reducing the ubiquitination and degradation of CREB, alleviating hepatic I/R injury. Nature Publishing Group UK 2022-03-08 /pmc/articles/PMC8904859/ /pubmed/35260558 http://dx.doi.org/10.1038/s41420-021-00784-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Yi-Liang
Zhang, Ying
Cai, Da-Sheng
Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis
title Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis
title_full Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis
title_fullStr Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis
title_full_unstemmed Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis
title_short Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis
title_sort hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microrna-124-3p-mediated traf3/creb axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904859/
https://www.ncbi.nlm.nih.gov/pubmed/35260558
http://dx.doi.org/10.1038/s41420-021-00784-7
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