Li Ruijin, Kou Xiaojing, Geng Hong, Xie Jingfang, Yang Zhenhua, Zhang Yuexia, Cai Zongwei, Dong Chuan
Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University , Taiyuan 030006, China.
Chem Res Toxicol. 2015 Mar 16;28(3):408-18. doi: 10.1021/tx5003723. Epub 2015 Jan 16.
Exposure to ambient fine particulate matter (PM2.5) increases the risk of respiratory disease. Although previous mitochondrial research has provided new information about PM toxicity in the lung, the exact mechanism of PM2.5-mediated structural and functional damage of lung mitochondria remains unclear. In this study, changes in lung mitochondrial morphology, expression of mitochondrial fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM2.5 at different dosages were investigated. Also, the release of reactive oxygen species (ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed to PM2.5 was examined by luminol-dependent chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung and induced pathological damage, particularly causing abnormal alterations of mitochondrial structure, including mitochondrial swelling and cristae disorder or even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5 significantly affected the expression of specific mitochondrial fission/fusion markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM2.5 inhibited Mn superoxide dismutase (MnSOD), Na(+)K(+)-ATPase, and Ca(2+)-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM2.5 induced rat AMs to produce ROS, which was inhibited by about 84.1% by diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is suggested that the pathological injury observed in rat lung exposed to PM2.5 is associated with mitochondrial fusion-fission dysfunction, ROS generation, mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to lung mitochondria may be one of the important mechanisms by which PM2.5 induces lung injury, contributing to respiratory diseases.
暴露于环境细颗粒物（PM2.5）会增加患呼吸道疾病的风险。尽管先前的线粒体研究提供了有关肺部PM毒性的新信息，但PM2.5介导的肺线粒体结构和功能损伤的确切机制仍不清楚。在本研究中，调查了不同剂量环境PM2.5暴露的SD大鼠肺线粒体形态变化、线粒体分裂/融合标志物的表达、脂质过氧化和转运ATP酶活性。此外，通过鲁米诺依赖性化学发光（CL）检测了暴露于PM2.5的大鼠肺泡巨噬细胞（AM）中呼吸爆发产生的活性氧（ROS）释放。结果表明：（1）PM2.5沉积在肺中并引起病理损伤，特别是导致线粒体结构异常改变，包括线粒体肿胀、嵴紊乱，甚至在高剂量PM2.5存在时出现碎片化；（2）PM2.5显著影响大鼠肺中特定线粒体分裂/融合标志物（OPA1、Mfn1、Mfn2、Fis1和Drp1）的表达；（3）PM2.5抑制大鼠肺线粒体中的锰超氧化物歧化酶（MnSOD）、Na(+)K(+)-ATP酶和Ca(2+)-ATP酶活性，并提高丙二醛（MDA）含量；（4）PM2.5诱导大鼠AM产生ROS，重要的ROS生成抑制剂二苯基碘鎓氯化物（DPI）可抑制约84.1%的ROS产生。提示暴露于PM2.5的大鼠肺中观察到的病理损伤与线粒体融合-分裂功能障碍、ROS产生、线粒体脂质过氧化和细胞内稳态失衡有关。肺线粒体损伤可能是PM2.5诱导肺损伤并导致呼吸道疾病的重要机制之一。
