Department of Pharmacology, Dalian Medical University, Dalian, China.
Institute of Integrative Medicine, Dalian Medical University, Dalian, China.
Front Immunol. 2021 May 13;12:652782. doi: 10.3389/fimmu.2021.652782. eCollection 2021.
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.
细胞焦亡是一种新发现的细胞死亡形式。过氧化物酶 3（PRX3）在清除活性氧（ROS）方面发挥着关键作用，但它在对乙酰氨基酚（APAP）诱导的肝病中的肝保护作用尚不清楚。本研究旨在评估 PRX3 在调控 APAP 介导的肝毒性过程中细胞焦亡中的作用。我们的研究结果表明，细胞焦亡发生在伴有强烈氧化应激和炎症的 APAP 诱导的肝损伤中，而肝特异性 PRX3 沉默加剧了 APAP 干预后的细胞焦亡和肝损伤的起始。值得注意的是，过量的线粒体 ROS（mtROS）通过激活 NLRP3 炎性小体被观察到触发细胞焦亡，而 Mito-TEMPO 处理可改善这一现象，表明 PRX3 的抗细胞焦亡作用依赖于其对 mtROS 的强大调节能力。总的来说，PRX3 通过靶向线粒体氧化应激调节 APAP 诱导的肝损伤中的 NLRP3 依赖性细胞焦亡。
