Tianjin Institute of Environmental and Operational Medicine, No. 1 Dali Road, Heping District, Tianjin 300050, China.
Tianjin Institute of Environmental and Operational Medicine, No. 1 Dali Road, Heping District, Tianjin 300050, China; Binzhou Medical College, Yantai 264000, China.
Ecotoxicol Environ Saf. 2022 Jul 15;240:113663. doi: 10.1016/j.ecoenv.2022.113663. Epub 2022 May 26.
To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells.
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.
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.
研究臭氧诱导的肺上皮细胞自噬与细胞焦亡的调控关系。
首先，用不同剂量的臭氧处理 I 型肺泡上皮细胞和雄性 Wistar 大鼠。I 型肺泡上皮细胞中 ATP 含量和线粒体膜电位明显降低。自噬相关标志物和 PINK1/Parkin 通路相关蛋白，以及 LC3、Parkin 和线粒体在 I 型肺泡上皮细胞中的共定位表明，臭氧暴露引发了自噬。另一方面，活性氧（ROS）抑制剂 NAC 可显著减轻上皮细胞中的自噬。在用自噬抑制剂 MDIVI-1 处理后，细胞中 NLRP3 炎性小体、裂解的 caspase-1 和 N-gasdermin D（N-GSDMD）的水平显著降低。综上所述，这些结果表明臭氧暴露可引发自噬，进而通过 NLRP3 炎性小体诱导细胞死亡。最后，通过 NLRP3 的过表达和敲低证实了这一结论。
臭氧暴露引起氧化损伤，导致线粒体结构和功能损伤。臭氧诱导的 ROS 通过激活 PINK1/Parkin 信号通路触发自噬，然后通过激活 NLRP3 炎性小体引发细胞焦亡。
