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Activation of autophagy protects against cholestasis-induced hepatic injury
BACKGROUND: Cholestasis is characterized by an abnormal accumulation of bile acids and causes hepatocellular injury. Recent studies show that autophagy is involved in the pathophysiology of many liver diseases. The potential role of autophagy in preventing cholestatic hepatotoxicity, however, has ra...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412295/ https://www.ncbi.nlm.nih.gov/pubmed/25922659 http://dx.doi.org/10.1186/2045-3701-4-47 |
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author | Gao, Lu Lv, Gang Guo, Xianling Jing, Yingying Han, Zhipeng Zhang, Shanshan Sun, Kai Li, Rong Yang, Yang Wei, Lixin |
author_facet | Gao, Lu Lv, Gang Guo, Xianling Jing, Yingying Han, Zhipeng Zhang, Shanshan Sun, Kai Li, Rong Yang, Yang Wei, Lixin |
author_sort | Gao, Lu |
collection | PubMed |
description | BACKGROUND: Cholestasis is characterized by an abnormal accumulation of bile acids and causes hepatocellular injury. Recent studies show that autophagy is involved in the pathophysiology of many liver diseases. The potential role of autophagy in preventing cholestatic hepatotoxicity, however, has rarely been investigated. The aim of this study was to examine whether autophagy is involved in the cholestatic hepatotoxicity. RESULTS: We found that bile duct ligation (BDL) led to cholestatic liver injury and hepatocytic autophagy activation in the mice. Suppression of autophagy with Chloroquine (CQ) increased liver injury and hepatocytes apoptosis; while activation of autophagy by rapamycin reduced cholestasis hepatotoxicity. In L02 normal liver cells, Glycochenodeoxycholate (GCDC) treatment would induce autophagy. Inhibition of autophagy by CQ could promote GCDC-induced cell apoptosis. In contrast, rapamycin treatment could protect against GCDC-induced cell death. Furthermore, autophagy contributed to the liver cells survival via modulation of reactive oxygen species (ROS). CONCLUSIONS: These findings indicate that autophagy protects against cholestasis induced liver injury and hepatocyte apoptosis by eliminating ROS accumulation. Our data suggest that enhancement of autophagy may be a therapeutic strategy to mitigate cholestatic liver injury. |
format | Online Article Text |
id | pubmed-4412295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44122952015-04-29 Activation of autophagy protects against cholestasis-induced hepatic injury Gao, Lu Lv, Gang Guo, Xianling Jing, Yingying Han, Zhipeng Zhang, Shanshan Sun, Kai Li, Rong Yang, Yang Wei, Lixin Cell Biosci Research BACKGROUND: Cholestasis is characterized by an abnormal accumulation of bile acids and causes hepatocellular injury. Recent studies show that autophagy is involved in the pathophysiology of many liver diseases. The potential role of autophagy in preventing cholestatic hepatotoxicity, however, has rarely been investigated. The aim of this study was to examine whether autophagy is involved in the cholestatic hepatotoxicity. RESULTS: We found that bile duct ligation (BDL) led to cholestatic liver injury and hepatocytic autophagy activation in the mice. Suppression of autophagy with Chloroquine (CQ) increased liver injury and hepatocytes apoptosis; while activation of autophagy by rapamycin reduced cholestasis hepatotoxicity. In L02 normal liver cells, Glycochenodeoxycholate (GCDC) treatment would induce autophagy. Inhibition of autophagy by CQ could promote GCDC-induced cell apoptosis. In contrast, rapamycin treatment could protect against GCDC-induced cell death. Furthermore, autophagy contributed to the liver cells survival via modulation of reactive oxygen species (ROS). CONCLUSIONS: These findings indicate that autophagy protects against cholestasis induced liver injury and hepatocyte apoptosis by eliminating ROS accumulation. Our data suggest that enhancement of autophagy may be a therapeutic strategy to mitigate cholestatic liver injury. BioMed Central 2014-08-26 /pmc/articles/PMC4412295/ /pubmed/25922659 http://dx.doi.org/10.1186/2045-3701-4-47 Text en © Gao et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Gao, Lu Lv, Gang Guo, Xianling Jing, Yingying Han, Zhipeng Zhang, Shanshan Sun, Kai Li, Rong Yang, Yang Wei, Lixin Activation of autophagy protects against cholestasis-induced hepatic injury |
title | Activation of autophagy protects against cholestasis-induced hepatic injury |
title_full | Activation of autophagy protects against cholestasis-induced hepatic injury |
title_fullStr | Activation of autophagy protects against cholestasis-induced hepatic injury |
title_full_unstemmed | Activation of autophagy protects against cholestasis-induced hepatic injury |
title_short | Activation of autophagy protects against cholestasis-induced hepatic injury |
title_sort | activation of autophagy protects against cholestasis-induced hepatic injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412295/ https://www.ncbi.nlm.nih.gov/pubmed/25922659 http://dx.doi.org/10.1186/2045-3701-4-47 |
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