Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

被引：65

作者：

Wang, Yue ^{[1
,2
]}

Zhao, Yan ^{[1
]}

Wang, Zhecheng ^{[1
]}

Sun, Ruimin ^{[1
]}

Zou, Boyang ^{[1
]}

Li, Ruixi ^{[1
]}

Liu, Deshun ^{[3
]}

Lin, Musen ^{[4
]}

Zhou, Junjun ^{[1
]}

Ning, Shili ^{[3
]}

Tian, Xiaofeng ^{[3
]}

Yao, Jihong ^{[1
,2
]}

机构：

[1] Dalian Med Univ, Dept Pharmacol, Dalian, Peoples R China

[2] Dalian Med Univ, Inst Integrat Med, Dalian, Peoples R China

[3] Dalian Med Univ, Affiliated Hosp 2, Dept Gen Surg, Dalian, Peoples R China

[4] Dalian Med Univ, Affiliated Hosp 2, Dept Pharm, Dalian, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷

基金：

中国国家自然科学基金;

关键词：

PRX3; pyroptosis; mitochondrial ROS (mtROS); NLRP3; inflammasome; APAP;

D O I：

10.3389/fimmu.2021.652782

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.

引用

页数：13

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