HBx公司
肝细胞
肝损伤
体内
活力测定
程序性细胞死亡
乙型肝炎病毒
谷胱甘肽
化学
分子生物学
癌症研究
生物
体外
细胞凋亡
药理学
免疫学
生物化学
病毒
酶
生物技术
作者
Guozhen Liu,Xuwen Xu,Shuhui Tao,Ming-Jian Gao,Zhouhua Hou
标识
DOI:10.1186/s12929-021-00762-2
摘要
Abstract Background Acute liver failure (ALF) is a syndrome of severe hepatocyte injury with high rate of mortality. Hepatitis B virus (HBV) infection is the major cause of ALF worldwide, however, the underlying mechanism by which HBV infection leads to ALF has not been fully disclosed. Methods D-GalN-induced hepatocyte injury model and LPS/D-GalN-induced ALF mice model were used to investigate the effects of HBV X protein (HBx) in vitro and in vivo, respectively. Cell viability and the levels of Glutathione (GSH), malondialdehyde (MDA) and iron were measured using commercial kits. The expression of ferroptosis-related molecules were detected by qRT-PCR and western blotting. Epigenetic modification and protein interaction were detected by chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (co-IP), respectively. Mouse liver function was assessed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological changes in liver tissues were monitored by hematoxylin and eosin (H&E) staining, and SLC7A11 immunoreactivity was assessed by immunohistochemistry (IHC) analysis. Results D-GalN triggered ferroptosis in primary hepatocytes. HBx potentiated D-GalN-induced hepatotoxicity and ferroptosis in vitro, and it suppressed SLC7A11 expression through H3K27me3 modification by EZH2. In addition, EZH2 inhibition or SLC7A11 overexpression attenuated the effects of HBx on D-GalN-induced ferroptosis in primary hepatocytes. The ferroptosis inhibitor ferrostatin-1 (Fer-1) protected against ALF and ferroptosis in vivo. By contrast, HBx exacerbates LPS/D-GalN-induced ALF and ferroptosis in HBx transgenic (HBx-Tg) mice. Conclusion HBx facilitates ferroptosis in ALF via EZH2/H3K27me3-mediated SLC7A11 suppression.
科研通智能强力驱动
Strongly Powered by AbleSci AI