Ambient ozone exposure induces ROS related-mitophagy and pyroptosis via NLRP3 inflammasome activation in rat lung cells

Ecotoxicology and Environmental Safety

Kang Li¹  Yizhe Tan²  Jie Han²  Bencheng Lin²  Lei Tian²  Ning Li²  Wenqing Lai²  Zhuge Xi²  Yue Shi²  Huanliang Liu²  Xiaohua Liu² 

[1] Binzhou Medical College, Yantai 264000, China;Tianjin Institute of Environmental and Operational Medicine, No. 1 Dali Road, Heping District, Tianjin 300050, China;

关键词: Ozone;    Lung toxicity;    Reactive oxygen species;    Mitophagy;    Pyroptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective: To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. Results: First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. Conclusion: Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome.

【 授权许可】

Unknown