Brg1-mediated Nrf2/HO-1 pathway activation alleviates hepatic ischemia-reperfusion injury

被引：150

作者：

Ge, Mian ^{[1
]}

Yao, Weifeng ^{[1
]}

Yuan, Dongdong ^{[1
]}

Zhou, Shaoli ^{[1
]}

Chen, Xi ^{[1
]}

Zhang, Yihan ^{[1
]}

Li, Haobo ^{[2
,3
,4
]}

Xia, Zhengyuan ^{[2
,3
,4
]}

Hei, Ziqing ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Dept Anesthesiol, Affiliated Hosp 3, Guangzhou 510630, Guangdong, Peoples R China

[2] Univ Hong Kong, Dept Anesthesiol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China

[3] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Dept Med, Hong Kong, Hong Kong, Peoples R China

[4] Guangdong Med Univ, Affiliated Hosp, Dept Anesthesiol, Zhanjiang 524001, Guangdong, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

LIVER ISCHEMIA/REPERFUSION INJURY; HEME OXYGENASE-1; OXIDATIVE STRESS; REMODELING COMPLEXES; REACTIVE OXYGEN; NRF2; EXPRESSION; GENE; HEPATOCYTE; INDUCTION;

D O I：

10.1038/cddis.2017.236

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cytoprotective gene heme oxygenase 1 (HO-1) could be induced by nuclear factor E2-related factor 2 (Nrf2) nuclear translocation. The purpose of this study was to determine the role of Brahma-related gene 1 (Brg1), a catalytic subunit of SWI2/SNF2-like chromatin remodeling complexes, in Nrf2/HO-1 pathway activation during hepatic ischemia-reperfusion (HIR). Our results showed that hepatic Brg1 was inhibited during early HIR while Brg1 overexpression reduced oxidative injury in CMV-Brg1 mice subjected to HIR. Moreover, promoter-driven luciferase assay showed that overexpression of Brg1 by adenovirus transfection in AML12 cells selectively enhanced HO-1 gene expression after hypoxia/reoxygenation (H/R) treatment but did not affect the other Nrf2 target gene NQO1. Furthermore, inhibition of HO-1 by the selective HO-1 inhibitor zinc protoporphyria could partly reverse the hepatic protective effects of Brg1 overexpression while HO-1-Adv attenuated AML12 cells H/R damage. Further, chromatin immunoprecipitation analysis revealed that Brg1 overexpression, which could significantly increase the recruitment of Brg1 protein to HO-1 but not NQO1 promoter, was recruited by Nrf2 to the HO-1 regulatory regions in AML12 hepatocytes subjected to H/R. In conclusion, our results demonstrated that restoration of Brg1 during reperfusion could enhance Nrf2-mediated inducible expression of HO-1 during HIR to effectively increase antioxidant ability to combat against hepatocytes damage.

引用

页码：e2841 / e2841

页数：11

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