N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.

<h4>Background</h4>Hepatic ischemia-reperfusion injury (HIRI) remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcystein...

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Autores principales:	Chengfen Wang, Kan Chen, Yujing Xia, Weiqi Dai, Fan Wang, Miao Shen, Ping Cheng, Junshan Wang, Jie Lu, Yan Zhang, Jing Yang, Rong Zhu, Huawei Zhang, Jingjing Li, Yuanyuan Zheng, Yingqun Zhou, Chuanyong Guo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7bcb0cde7dd842948f75d3bc774f422e
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spelling	oai:doaj.org-article:7bcb0cde7dd842948f75d3bc774f422e2021-11-25T05:58:57ZN-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.1932-620310.1371/journal.pone.0108855https://doaj.org/article/7bcb0cde7dd842948f75d3bc774f422e2014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0108855https://doaj.org/toc/1932-6203<h4>Background</h4>Hepatic ischemia-reperfusion injury (HIRI) remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcysteine (NAC) has significant pharmacologic effects on HIRI including elimination of reactive oxygen species (ROS) and attenuation of hepatic apoptosis. However, the effects of NAC on HIRI-induced autophagy have not been reported. In this study, we evaluated the effects of NAC on autophagy and apoptosis in HIRI, and explored the possible mechanism involved.<h4>Methods</h4>A mouse model of segmental (70%) hepatic warm ischemia was adopted to determine hepatic injury. NAC (150 mg/kg), a hepatoprotection agent, was administered before surgery. We hypothesized that the mechanism of NAC may involve the ROS/JNK/Bcl-2 pathway. We evaluated the expression of JNK, P-JNK, Bcl-2, Beclin 1 and LC3 by western blotting and immunohistochemical staining. Autophagosomes were evaluated by transmission electron microscopy (TEM).<h4>Results</h4>We found that ALT, AST and pathological changes were significantly improved in the NAC group. Western blotting analysis showed that the expression levels of Beclin 1 and LC3 were significantly decreased in NAC-treated mice. In addition, JNK, p-JNK, Bax, TNF-α, NF-κB, IL2, IL6 and levels were also decreased in NAC-treated mice.<h4>Conclusion</h4>NAC can prevent HIRI-induced autophagy and apoptosis by influencing the JNK signal pathway. The mechanism is likely to involve attenuation of JNK and p-JNK via scavenged ROS, an indirect increase in Bcl-2 level, and finally an alteration in the balance of Beclin 1 and Bcl-2.Chengfen WangKan ChenYujing XiaWeiqi DaiFan WangMiao ShenPing ChengJunshan WangJie LuYan ZhangJing YangRong ZhuHuawei ZhangJingjing LiYuanyuan ZhengYingqun ZhouChuanyong GuoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e108855 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chengfen Wang Kan Chen Yujing Xia Weiqi Dai Fan Wang Miao Shen Ping Cheng Junshan Wang Jie Lu Yan Zhang Jing Yang Rong Zhu Huawei Zhang Jingjing Li Yuanyuan Zheng Yingqun Zhou Chuanyong Guo N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.
description	<h4>Background</h4>Hepatic ischemia-reperfusion injury (HIRI) remains a pivotal clinical problem after hemorrhagic shock, transplantation, and some types of toxic hepatic injury. Apoptosis and autophagy play important roles in cell death during HIRI. It is also known that N-acetylcysteine (NAC) has significant pharmacologic effects on HIRI including elimination of reactive oxygen species (ROS) and attenuation of hepatic apoptosis. However, the effects of NAC on HIRI-induced autophagy have not been reported. In this study, we evaluated the effects of NAC on autophagy and apoptosis in HIRI, and explored the possible mechanism involved.<h4>Methods</h4>A mouse model of segmental (70%) hepatic warm ischemia was adopted to determine hepatic injury. NAC (150 mg/kg), a hepatoprotection agent, was administered before surgery. We hypothesized that the mechanism of NAC may involve the ROS/JNK/Bcl-2 pathway. We evaluated the expression of JNK, P-JNK, Bcl-2, Beclin 1 and LC3 by western blotting and immunohistochemical staining. Autophagosomes were evaluated by transmission electron microscopy (TEM).<h4>Results</h4>We found that ALT, AST and pathological changes were significantly improved in the NAC group. Western blotting analysis showed that the expression levels of Beclin 1 and LC3 were significantly decreased in NAC-treated mice. In addition, JNK, p-JNK, Bax, TNF-α, NF-κB, IL2, IL6 and levels were also decreased in NAC-treated mice.<h4>Conclusion</h4>NAC can prevent HIRI-induced autophagy and apoptosis by influencing the JNK signal pathway. The mechanism is likely to involve attenuation of JNK and p-JNK via scavenged ROS, an indirect increase in Bcl-2 level, and finally an alteration in the balance of Beclin 1 and Bcl-2.
format	article
author	Chengfen Wang Kan Chen Yujing Xia Weiqi Dai Fan Wang Miao Shen Ping Cheng Junshan Wang Jie Lu Yan Zhang Jing Yang Rong Zhu Huawei Zhang Jingjing Li Yuanyuan Zheng Yingqun Zhou Chuanyong Guo
author_facet	Chengfen Wang Kan Chen Yujing Xia Weiqi Dai Fan Wang Miao Shen Ping Cheng Junshan Wang Jie Lu Yan Zhang Jing Yang Rong Zhu Huawei Zhang Jingjing Li Yuanyuan Zheng Yingqun Zhou Chuanyong Guo
author_sort	Chengfen Wang
title	N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.
title_short	N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.
title_full	N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.
title_fullStr	N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.
title_full_unstemmed	N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.
title_sort	n-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ros/jnk/bcl-2 pathway.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7bcb0cde7dd842948f75d3bc774f422e
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N-acetylcysteine attenuates ischemia-reperfusion-induced apoptosis and autophagy in mouse liver via regulation of the ROS/JNK/Bcl-2 pathway.

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