炎症体
MFN2型
上睑下垂
酒精性肝病
化学
肝细胞
细胞生物学
肝保护
药理学
线粒体ROS
线粒体
癌症研究
医学
生物
线粒体融合
受体
生物化学
内科学
谷胱甘肽
线粒体DNA
基因
肝硬化
体外
酶
作者
Jun Kai,Yang Xiang,Zhimin Wang,Feixia Wang,Yan Jia,Shijun Wang,Shanzhong Tan,Anping Chen,Jiangjuan Shao,Feng Zhang,Zili Zhang,Shizhong Zheng
标识
DOI:10.1016/j.freeradbiomed.2020.03.031
摘要
It is well acknowledged that alcoholic liver disease (ALD) is widely prevalent all over the world, characterized by aberrant lipid deposition and excessive oxidative stress in hepatocytes. Recently, pyroptosis, a new type of programmed cell death, has been found in ALD, which provides new ideas for the treatment of ALD. Male ICR mice were treated with the Lieber-De-Carli diet (Dyets) or isocaloric liquid diet for 8 weeks, and binge alcohol model was also used for ALD. Blood and livers were taken to evaluate the efficacy of oroxylin A. The levels of factors related to hepatocyte pyroptosis were measured via western blot analyses, immunofluorescence analyses and quantitative reverse transcriptase in vitro. Our study found that oroxylin A suppressed hepatocyte pyroptosis through a NLRP3 inflammasome dependent-canonical caspase-1 pathway. Results illuminated that oroxylin A inhibited NLRP3 inflammasome activation by reducing ROS accumulation. Furthermore, oroxylin A upregulated mitofusin 2 (Mfn2) to resist lipid deposition and mitochondria-derived ROS overproduction. As an upstream mediator of Mfn2, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a major regulator of mitochondria, was found to promote transcription of Mfn2 under oroxylin A treatment. Our research revealed that oroxylin A could alleviate ALD via PGC-1α/Mfn2 signaling mediated canonical pyroptosis pathway resistance.
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