PM2.5 increases susceptibility to acute exacerbation of COPD via NOX4/Nrf2 redox imbalance-mediated mitophagy.
PM2.5 increases susceptibility to acute exacerbation of COPD via NOX4/Nrf2 redox imbalance-mediated mitophagy.
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PM2.5 通过 NOX4/Nrf2 氧化还原失衡介导的线粒体自噬增加 COPD 急性加重的易感性
DOI：
10.1016/j.redox.2022.102587
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发表时间：
2023-02
期刊：
影响因子：
11.4
通讯作者：
Peng, Liping
中科院分区：
文献类型：
--
作者：
Fan, Xiaoye;Dong, Tingting;Yan, Kun;Ci, Xinxin;Peng, Liping
The increasing abundance of fine particulate matter (PM2.5) in the environment has increased susceptibility to acute exacerbation of COPD (AECOPD). During PM2.5 exposure, excessive reactive oxygen species (ROS) production triggers a redox imbalance, which contributes to damage to organelles and disruption of homeostasis. At present, there are limited data on whether NOX4/Nrf2 redox imbalance increases susceptibility to acute exacerbation of COPD (AECOPD), and the underlying mechanism is unclear. Therefore, the current study was aimed to evaluate the role of NOX4/Nrf2 redox balance on AECOPD induced by PM2.5-CS-exposure. Here, we report that PM2.5 exacerbates cytotoxicity by enhancing NOX4/Nrf2 redox imbalance-mediated mitophagy. First, exposure to a low-dose of PM2.5 (200 μg/ml) significantly exacerbated oxidative stress and mitochondrial damage by increasing the ROS overproduction, enhancing the excessive NOX4/Nrf2 redox imbalance, decreasing the mitochondrial membrane potential (MMP), and enhancing the mitochondrial fragmentation that were caused by a low-dose of CSE (2.5%). Second, coexposure to PM2.5 and CSE (PM2.5-CSE) induced excessive mitophagy. Third, PM2.5 exacerbated CS-induced COPD, as shown by excessive inflammatory cell infiltration, inflammatory cytokine production and mucus hypersecretion, goblet cell hyperplasia, NOX4/Nrf2 redox imbalance, and mitophagy, these effects triggered excessive ROS production and mitochondrial damage in mice. Mechanistically, PM2.5-CS-induced excessive levels of mitophagy by triggering redox imbalance, leading to greater cytotoxicity and AECOPD; however, reestablishing the NOX4/Nrf2 redox balance via NOX4 blockade or mitochondria-specific ROS inhibitor treatment alleviated this cytotoxicity and ameliorated AECOPD. PM2.5 may exacerbate NOX4/Nrf2 redox imbalance and subsequently enhance mitophagy by increasing the ROS and mito-ROS levels, thereby increasing susceptibility to AECOPD.
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影响因子：
6.8
作者：
Qiu, Yi-Ning;Wang, Guo-Hui;Zhang, Ke-Zhong
通讯作者：
Zhang, Ke-Zhong
影响因子：
11.4
作者：
Quijano C;Trujillo M;Castro L;Trostchansky A
通讯作者：
Trostchansky A
DOI：
10.1046/j.1524-4733.2001.45049.x
发表时间：
2001-09-01
期刊：
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research
影响因子：
--
作者：
McGuire, A;Irwin, D E;MacGowan, A
通讯作者：
MacGowan, A
影响因子：
4.4
作者：
Valenzuela, Rodrigo;Angel Rincon-Cervera, Miguel;Videla, Luis A.
通讯作者：
Videla, Luis A.
影响因子：
8.3
作者：
Sun, Xian Wen;Lin, Ying Ni;Li, Qing Yun
通讯作者：
Li, Qing Yun