Dihydroartemisinin inhibits ER stress-mediated mitochondrial pathway to attenuate hepatocyte lipoapoptosis via blocking the activation of the PI3K/Akt pathway

被引：27

作者：

Chen, Xingran ^{[1
]}

Bian, Mianli ^{[1
]}

Zhang, Chenxi ^{[1
]}

Kai, Jun ^{[1
]}

Yao, Zhen ^{[1
]}

Jin, Huanhuan ^{[1
]}

Lu, Chunfeng ^{[1
]}

Shao, Jiangjuan ^{[2
]}

Chen, Anping ^{[3
]}

Zhang, Feng ^{[1
]}

Zheng, Shizhong ^{[1
,4
]}

机构：

[1] Nanjing Univ Chinese Med, Dept Pharmacol, Coll Pharm, 138 Xianlin Ave, Nanjing 210023, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Dept Pharm, Coll Pharm, Nanjing 210023, Jiangsu, Peoples R China

[3] St Louis Univ, Dept Pathol, Sch Med, St Louis, MO 63104 USA

[4] Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing, Jiangsu, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2018年 / 97卷

基金：

中国国家自然科学基金;

关键词：

Alcoholic liver disease; Dihydroartemisinin; Hepatic steatosis; Lipoapoptosis; ALCOHOLIC LIVER-INJURY; OXIDATIVE STRESS; STEATOSIS; APOPTOSIS; DISEASE; STEATOHEPATITIS; LIPOTOXICITY; AUTOPHAGY;

D O I：

10.1016/j.biopha.2017.11.010

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Alcoholic liver disease (ALD), characterized by accumulation of fatty acids in liver cells, is usually caused by Chronic alcohol consumption. Our previous study has identified that DA protects against alcoholic liver injury in alcohol-fed rats through alleviating hepatocyte steatosis. It has emerged that saturated fatty acids could provoke endoplasmic reticulum (ER) stress and apoptosis in hepatocytes. This study was aimed to explore the impact of DA on ALD and further elaborate the underlying mechanisms. Results demonstrated that DA attenuates alcoholic liver injury in mice. Our results also indicated that DA attenuated lipid accumulation in hepatocytes exposed to ethanol. DA attenuates ethanol-induced hepatocyte apoptosis. Results demonstrated that DA dose-dependently ameliorated activation of mitochondrial pathway activation, which plays a critical role in apoptosis attributed to lipotoxicity. Further, DA suppressed the activation of JNK and the expression of CHOP, attributed to the inhibition of ER stress. It has emerged that activation of ER stress-JNK/CHOP-mitochondria cascade is considered as the key mechanisms underlying hepatocyte lipoapoptosis. In addition, DA attenuates PI3K/Akt Pathway in hepatocytes, consistent with our previous finding in HSCs. DA effects were reinforced by PI3K specific inhibitor LY294002. In summary, DA significantly protected hepatocytes against lipoapoptosis via a PI3K/Akt Pathway inhibition-dependent mechanism.

引用

页码：975 / 984

页数：10

共 33 条

[1]

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