Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS.
Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS.
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Peroxiredoxin 3 通过调节线粒体 ROS 抑制对乙酰氨基酚诱导的肝焦亡
DOI：
10.3389/fimmu.2021.652782
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yao J
中科院分区：
文献类型：
--
作者：
Wang Y;Zhao Y;Wang Z;Sun R;Zou B;Li R;Liu D;Lin M;Zhou J;Ning S;Tian X;Yao J
焦亡是一种新发现的细胞死亡形式。过氧化物氧还蛋白3（PRX 3）在清除活性氧（ROS）中起着至关重要的作用，但其在对乙酰氨基酚（APAP）诱导的肝病中的肝保护能力尚不清楚。本研究的目的是评估PRX 3在APAP介导的肝毒性过程中调节焦亡的作用。我们证明了在APAP诱导的肝损伤中发生焦亡，伴随着强烈的氧化应激和炎症，并且肝脏特异性PRX 3沉默加重了APAP干预后焦亡和肝损伤的起始。值得注意的是，观察到过量的线粒体ROS（mtROS）通过激活NLRP 3炎性体而触发细胞凋亡，这通过Mito-TEMPO处理得到改善，表明PRX 3的抗细胞凋亡作用依赖于其调节mtROS的强大能力。总体而言，PRX 3通过靶向线粒体氧化应激调节APAP诱导的肝损伤中NLRP 3依赖性焦亡。
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.
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影响因子：
25.7
作者：
Gaul S;Leszczynska A;Alegre F;Kaufmann B;Johnson CD;Adams LA;Wree A;Damm G;Seehofer D;Calvente CJ;Povero D;Kisseleva T;Eguchi A;McGeough MD;Hoffman HM;Pelegrin P;Laufs U;Feldstein AE
通讯作者：
Feldstein AE
影响因子：
12.4
作者：
de Vasconcelos NM;Van Opdenbosch N;Van Gorp H;Parthoens E;Lamkanfi M
通讯作者：
Lamkanfi M
影响因子：
3.5
作者：
Khayyat, Ahdab;Tobwala, Shakila;Ercal, Nuran
通讯作者：
Ercal, Nuran
DOI：
10.1016/bs.apha.2018.12.004
发表时间：
2019-01-01
期刊：
Advances in pharmacology (San Diego, Calif.)
影响因子：
--
作者：
Fisher, Erik S;Curry, Steven C
通讯作者：
Curry, Steven C
影响因子：
7.3
作者：
Kilkenny, Carol;Browne, William;Altman, Douglas G.
通讯作者：
Altman, Douglas G.