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Autophagy lessens ischemic liver injury by reducing oxidative damage

BACKGROUND: Hepatic ischemia/reperfusion is a multi-factorial process which causes liver injury. It is reported that ischemia alone is sufficient to induce liver injury. Nutrient deprivation is a crucial factor impacting ischemic injury of the liver. Therefore, we explored the role of autophagy in i...

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Autores principales: Sun, Kai, Xie, Xuqin, Liu, Yan, Han, Zhipeng, Zhao, Xue, Cai, Ning, Zhang, Shanshan, Song, Jianrui, Wei, Lixin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693965/
https://www.ncbi.nlm.nih.gov/pubmed/23758862
http://dx.doi.org/10.1186/2045-3701-3-26
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author Sun, Kai
Xie, Xuqin
Liu, Yan
Han, Zhipeng
Zhao, Xue
Cai, Ning
Zhang, Shanshan
Song, Jianrui
Wei, Lixin
author_facet Sun, Kai
Xie, Xuqin
Liu, Yan
Han, Zhipeng
Zhao, Xue
Cai, Ning
Zhang, Shanshan
Song, Jianrui
Wei, Lixin
author_sort Sun, Kai
collection PubMed
description BACKGROUND: Hepatic ischemia/reperfusion is a multi-factorial process which causes liver injury. It is reported that ischemia alone is sufficient to induce liver injury. Nutrient deprivation is a crucial factor impacting ischemic injury of the liver. Therefore, we explored the role of autophagy in ischemia through using hepatic ischemia rat model in vivo and nutrient-free model in vitro. RESULTS: We found that both ischemia in vivo and nutrient deprivation in vitro activated autophagy, inhibition of which aggravated ischemia- or nutrient deficiency-induced injury. In the nutrient-free condition, autophagy inhibition enhanced liver cell necrosis but not apoptosis by promoting reactive oxygen species (ROS) accumulation, and antioxidant NAC could reverse this trend. Inhibition of autophagy also resulted in the increase of the percentage of necrotic cell but not apoptotic cell in the ischemia-treated rat livers. Further studies showed that under nutrient deprivation, autophagy inhibition promoted mitochondrial ROS generation, which further aggravated mitochondria damage. These changes formed a “vicious cycle” that accelerated the process of cell necrosis. Autophagy inhibition also increased mitochondrial oxidative stress during hepatic ischemia, and antioxidant could suppress the aggravation of ischemia-induced liver damage in the co-treatment of autophagy inhibitor. CONCLUSIONS: Taken together, our results suggested that autophagy suppressed ischemic liver injury by reducing ROS-induced necrosis. This finding will contribute to the development of the therapeutic strategy about the pre-treatment of liver surgery.
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spelling pubmed-36939652013-06-27 Autophagy lessens ischemic liver injury by reducing oxidative damage Sun, Kai Xie, Xuqin Liu, Yan Han, Zhipeng Zhao, Xue Cai, Ning Zhang, Shanshan Song, Jianrui Wei, Lixin Cell Biosci Research BACKGROUND: Hepatic ischemia/reperfusion is a multi-factorial process which causes liver injury. It is reported that ischemia alone is sufficient to induce liver injury. Nutrient deprivation is a crucial factor impacting ischemic injury of the liver. Therefore, we explored the role of autophagy in ischemia through using hepatic ischemia rat model in vivo and nutrient-free model in vitro. RESULTS: We found that both ischemia in vivo and nutrient deprivation in vitro activated autophagy, inhibition of which aggravated ischemia- or nutrient deficiency-induced injury. In the nutrient-free condition, autophagy inhibition enhanced liver cell necrosis but not apoptosis by promoting reactive oxygen species (ROS) accumulation, and antioxidant NAC could reverse this trend. Inhibition of autophagy also resulted in the increase of the percentage of necrotic cell but not apoptotic cell in the ischemia-treated rat livers. Further studies showed that under nutrient deprivation, autophagy inhibition promoted mitochondrial ROS generation, which further aggravated mitochondria damage. These changes formed a “vicious cycle” that accelerated the process of cell necrosis. Autophagy inhibition also increased mitochondrial oxidative stress during hepatic ischemia, and antioxidant could suppress the aggravation of ischemia-induced liver damage in the co-treatment of autophagy inhibitor. CONCLUSIONS: Taken together, our results suggested that autophagy suppressed ischemic liver injury by reducing ROS-induced necrosis. This finding will contribute to the development of the therapeutic strategy about the pre-treatment of liver surgery. BioMed Central 2013-06-10 /pmc/articles/PMC3693965/ /pubmed/23758862 http://dx.doi.org/10.1186/2045-3701-3-26 Text en Copyright © 2013 Sun et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Sun, Kai
Xie, Xuqin
Liu, Yan
Han, Zhipeng
Zhao, Xue
Cai, Ning
Zhang, Shanshan
Song, Jianrui
Wei, Lixin
Autophagy lessens ischemic liver injury by reducing oxidative damage
title Autophagy lessens ischemic liver injury by reducing oxidative damage
title_full Autophagy lessens ischemic liver injury by reducing oxidative damage
title_fullStr Autophagy lessens ischemic liver injury by reducing oxidative damage
title_full_unstemmed Autophagy lessens ischemic liver injury by reducing oxidative damage
title_short Autophagy lessens ischemic liver injury by reducing oxidative damage
title_sort autophagy lessens ischemic liver injury by reducing oxidative damage
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693965/
https://www.ncbi.nlm.nih.gov/pubmed/23758862
http://dx.doi.org/10.1186/2045-3701-3-26
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