title: Effect of ambient PM(2.5) on lung mitochondrial damage and fusion/fission gene expression in rats.
abstract: 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.
authors.affiliation: Institute of Environmental Science, College of Environmental & Resource Sciences, Shanxi University , Taiyuan 030006, China.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Li
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Kou
authors.forename: Hong
authors.initials: H
authors.lastname: Geng
authors.forename: Jingfang
authors.initials: J
authors.lastname: Xie
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Cai
authors.forename: Chuan
authors.initials: C
authors.lastname: Dong
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D024101:Mitochondrial Proteins; D052638:Particulate Matter; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase