Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury

Yongqing Cai1 *,* Bin Li1 *,* Dan Peng,1 Xianfeng Wang,1 Pan Li,2 Mingchun Huang,3 Haiyan Xing,1 Jianhong Chen1 1Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Pharmacy, Fengdu Traditional Chinese Medicine Hos...

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Autores principales:	Cai Y, Li B, Peng D, Wang X, Li P, Huang M, Xing H, Chen J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hyperoside oxidative stress bach1 crm1 hepatoprotective Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d6db67398670452dbb38a9816c8b45d3
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spelling	oai:doaj.org-article:d6db67398670452dbb38a9816c8b45d32021-12-02T16:22:18ZCrm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury1178-7031https://doaj.org/article/d6db67398670452dbb38a9816c8b45d32021-02-01T00:00:00Zhttps://www.dovepress.com/crm1-dependent-nuclear-export-of-bach1-is-involved-in-the-protective-e-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Yongqing Cai1 , Bin Li1 , Dan Peng,1 Xianfeng Wang,1 Pan Li,2 Mingchun Huang,3 Haiyan Xing,1 Jianhong Chen1 1Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Pharmacy, Fengdu Traditional Chinese Medicine Hospital, Chongqing, 408299, People’s Republic of China; 3Department of Pharmacy, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhong ChenDepartment of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of ChinaTel +86 23 6875 7091Email chenjh-110@263.netBackground: Nrf2-Bach1 antioxidant signaling pathway is considered as one of the most important mechanisms of cellular resistance to oxidative injury. The effect of hyperoside (Hyp) on the expression and distribution of Bach1, the relationship of Hyp’s antioxidative effect and the influence of Bach1 remains unclear.Purpose: The aim of this study was to investigate the role and mechanisms of Bach1 in the protective effect of Hyp on oxidative liver injury.Methods: The protective effect of Hyp on oxidative stress injury was observed in vivo and in vitro. Next, the influence of Hyp on Bach1 expression and distribution, and competitive combination of Nrf2-Bach1 with ARE in H2O2-induced L02 cell was studied by Western blot, RT-PCR, immunofluorescence and CHIP assay. Finally, the expressions of Crm1, ERK and p38 and their roles on Hyp mediated nuclear export of Bach1 were investigated by Western blot.Results: Hyp ameliorated the pathological damage, reduced the liver index, AST, ALT and MDA activities, and increased SOD and GSH levels in the CCl4-induced acute liver injury mouse model. Hyp attenuated H2O2-induced oxidative stress injury in L02 cells. Hyp promoted the early rapid redistribution of Bach1 from nucleus to cytoplasm. CHIP analyses demonstrated that Hyp enhanced the levels of Nrf2-ARE complex, and weakened the levels of Bach1-ARE complex within three hours. In addition, Hyp enhanced transport protein Crm1 expression and ERK1/2 activity. And LMB, a Crm1 inhibitor, attenuated the effect of Hyp on Bach1 nuclear export and anti-oxidation. U0126, an ERK1/2 inhibitor, reduced the effect of Hyp on Crm1 expression and the Bach1 redistribution.Conclusion: The hepatoprotective mechanism of Hyp was related to improve Bach1 nuclear export depending on ERK1/2-Crm1 to upregulate the level of Nrf2 binding to ARE.Keywords: hyperoside, oxidative stress, Bach1, Crm1, hepatoprotectiveCai YLi BPeng DWang XLi PHuang MXing HChen JDove Medical Pressarticlehyperosideoxidative stressbach1crm1hepatoprotectivePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 551-565 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyperoside oxidative stress bach1 crm1 hepatoprotective Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	hyperoside oxidative stress bach1 crm1 hepatoprotective Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Cai Y Li B Peng D Wang X Li P Huang M Xing H Chen J Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury
description	Yongqing Cai1 , Bin Li1 , Dan Peng,1 Xianfeng Wang,1 Pan Li,2 Mingchun Huang,3 Haiyan Xing,1 Jianhong Chen1 1Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Pharmacy, Fengdu Traditional Chinese Medicine Hospital, Chongqing, 408299, People’s Republic of China; 3Department of Pharmacy, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhong ChenDepartment of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of ChinaTel +86 23 6875 7091Email chenjh-110@263.netBackground: Nrf2-Bach1 antioxidant signaling pathway is considered as one of the most important mechanisms of cellular resistance to oxidative injury. The effect of hyperoside (Hyp) on the expression and distribution of Bach1, the relationship of Hyp’s antioxidative effect and the influence of Bach1 remains unclear.Purpose: The aim of this study was to investigate the role and mechanisms of Bach1 in the protective effect of Hyp on oxidative liver injury.Methods: The protective effect of Hyp on oxidative stress injury was observed in vivo and in vitro. Next, the influence of Hyp on Bach1 expression and distribution, and competitive combination of Nrf2-Bach1 with ARE in H2O2-induced L02 cell was studied by Western blot, RT-PCR, immunofluorescence and CHIP assay. Finally, the expressions of Crm1, ERK and p38 and their roles on Hyp mediated nuclear export of Bach1 were investigated by Western blot.Results: Hyp ameliorated the pathological damage, reduced the liver index, AST, ALT and MDA activities, and increased SOD and GSH levels in the CCl4-induced acute liver injury mouse model. Hyp attenuated H2O2-induced oxidative stress injury in L02 cells. Hyp promoted the early rapid redistribution of Bach1 from nucleus to cytoplasm. CHIP analyses demonstrated that Hyp enhanced the levels of Nrf2-ARE complex, and weakened the levels of Bach1-ARE complex within three hours. In addition, Hyp enhanced transport protein Crm1 expression and ERK1/2 activity. And LMB, a Crm1 inhibitor, attenuated the effect of Hyp on Bach1 nuclear export and anti-oxidation. U0126, an ERK1/2 inhibitor, reduced the effect of Hyp on Crm1 expression and the Bach1 redistribution.Conclusion: The hepatoprotective mechanism of Hyp was related to improve Bach1 nuclear export depending on ERK1/2-Crm1 to upregulate the level of Nrf2 binding to ARE.Keywords: hyperoside, oxidative stress, Bach1, Crm1, hepatoprotective
format	article
author	Cai Y Li B Peng D Wang X Li P Huang M Xing H Chen J
author_facet	Cai Y Li B Peng D Wang X Li P Huang M Xing H Chen J
author_sort	Cai Y
title	Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury
title_short	Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury
title_full	Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury
title_fullStr	Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury
title_full_unstemmed	Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury
title_sort	crm1-dependent nuclear export of bach1 is involved in the protective effect of hyperoside on oxidative damage in hepatocytes and ccl4-induced acute liver injury
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/d6db67398670452dbb38a9816c8b45d3
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Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury

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