FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy

Abstract FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. Howe...

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Autores principales:	Enshuang Guo, Renlong Li, Jiankun Yang, Jun Zhang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/000477d9d4174f0b8016ec4b3ee915b7
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spelling	oai:doaj.org-article:000477d9d4174f0b8016ec4b3ee915b72021-12-02T11:40:33ZFK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy10.1038/s41598-017-02318-72045-2322https://doaj.org/article/000477d9d4174f0b8016ec4b3ee915b72017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02318-7https://doaj.org/toc/2045-2322Abstract FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy. In vivo, Mice were pretreated with FK866 at 24, 12, and 0.5 h before treatment with GaIN/LPS and ConA. 3-methyladenine (3MA) or rapamycin were used to determine the role of autophagy in FK866-conferred hepatoprotection. In primary hepatocytes, autophagy was inhibited by 3MA or autophagy-related protein 7 (Atg7) small interfering RNA (siRNA). JNK was suppressed by SP600125 or Jnk siRNA. FK866 alleviated hepatotoxicity and increased autophagy while decreased JNK activation. Suppression of autophagy abolished the FK866-conferred protection. Inhibition of JNK increased autophagy and exhibited strongly protective effect. Collectively, FK866 could ameliorate GaIN/LPS and ConA-induced ALF through induction of autophagy while suppression of JNK. These findings suggest that FK866 acts as a simple and applicable preconditioning intervention to protect against ALF; autophagy and JNK may also provide therapeutic targets for ALF treatment.Enshuang GuoRenlong LiJiankun YangJun ZhangAnyi LiYan YangShenpei LiuAnding LiuXiaojing JiangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Enshuang Guo Renlong Li Jiankun Yang Jun Zhang Anyi Li Yan Yang Shenpei Liu Anding Liu Xiaojing Jiang FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
description	Abstract FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy. In vivo, Mice were pretreated with FK866 at 24, 12, and 0.5 h before treatment with GaIN/LPS and ConA. 3-methyladenine (3MA) or rapamycin were used to determine the role of autophagy in FK866-conferred hepatoprotection. In primary hepatocytes, autophagy was inhibited by 3MA or autophagy-related protein 7 (Atg7) small interfering RNA (siRNA). JNK was suppressed by SP600125 or Jnk siRNA. FK866 alleviated hepatotoxicity and increased autophagy while decreased JNK activation. Suppression of autophagy abolished the FK866-conferred protection. Inhibition of JNK increased autophagy and exhibited strongly protective effect. Collectively, FK866 could ameliorate GaIN/LPS and ConA-induced ALF through induction of autophagy while suppression of JNK. These findings suggest that FK866 acts as a simple and applicable preconditioning intervention to protect against ALF; autophagy and JNK may also provide therapeutic targets for ALF treatment.
format	article
author	Enshuang Guo Renlong Li Jiankun Yang Jun Zhang Anyi Li Yan Yang Shenpei Liu Anding Liu Xiaojing Jiang
author_facet	Enshuang Guo Renlong Li Jiankun Yang Jun Zhang Anyi Li Yan Yang Shenpei Liu Anding Liu Xiaojing Jiang
author_sort	Enshuang Guo
title	FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
title_short	FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
title_full	FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
title_fullStr	FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
title_full_unstemmed	FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
title_sort	fk866 attenuates acute hepatic failure through c-jun-n-terminal kinase (jnk)-dependent autophagy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/000477d9d4174f0b8016ec4b3ee915b7
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_version_	1718395559502413824

FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy

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