title: Roles of different mitochondrial electron transport chain complexes in hypoxia-induced pulmonary vasoconstriction.
abstract: This study was designed to investigate the roles of different mitochondrial electron transport chain (ETC) complexes (I, II, III, and IV) on hypoxia-induced hypoxic pulmonary vasoconstriction (HPV). The third and fourth pulmonary arteries were collected from the normal tissues adjacent to tumors in 16 patients with lung cancer who had undergone lung cancer resections to isolate pulmonary artery smooth muscle cells (PASMCs). PASMCs were divided into seven groups and exposed to one of the following treatments: (1) normoxia (21% O(2), 5% CO(2), and 74% N(2)); (2) hypoxia (1% O(2), 5% CO(2), 94% N(2)); (3) hypoxia plus ETC complex I inhibitor MPP; (4) hypoxia plus ETC complex II inhibitor TTFA; (5) hypoxia plus ETC complex III Q(o) (pre) site inhibitor myxothiazol; (6) hypoxia plus ETC complex III Qi (post) site inhibitor antimycin A; (7) hypoxia plus ETC complex IV inhibitor NaN(3). Intracellular [Ca(2+) ]i and [ROS]i, mitochondrial [ROS]i, and PA rings tension were measured. Intracellular [Ca(2+) ]i and [ROS]i, mitochondrial [ROS]i, and PA ring tension were increased after hypoxia for 10 min. Mitochondrial ETC complex inhibitor MPP, TTFA, and myxothiazol significantly reduced [Ca(2+) ]i [ROS]i and PA tension (P < 0.01), whereas antimycin A and NaN(3) did not effectively reduce them. These results demonstrated it were mitochondrial ETC complex I, II, and III Q(o) site but not III Q(i) site and complex IV contribute to hypoxic pulmonary vasoconstriction and pulmonary hypertension.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Ningxia People's Hospital, Yinchuan, 750011, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Ningxia People's Hospital, Yinchuan, 750011, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhuan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Ningxia People's Hospital, Yinchuan, 750011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Simin
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004579:Electron Transport / Q000502:physiology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D002118:Calcium
keywords: electron transport chain complex; hypoxia; hypoxic pulmonary vasoconstriction; pulmonary artery smooth muscle cells