title: Reactive oxygen species effect PASMCs apoptosis via regulation of dynamin-related protein 1 in hypoxic pulmonary hypertension.
abstract: The high level of reactive oxygen species and up-regulation of mitochondrial fission protein dynamin-related protein-1, both of which involved in pulmonary artery smooth muscle cells (PASMCs) apoptosis, have been detected in the lungs of rodent pulmonary arterial hypertension models. However, the regulatory mechanisms between ROS and DRP1 are poorly understood. In this study, ROS inhibitor, hypoxic rodent PAH models, small interfering RNA, polymerase chain reaction, Western blot, flow cytometry, immunohistochemistry and immunofluorescence were used. We determined that ROS, mainly derive from mitochondria, mediate mitochondria fission of PASMCs contributing to pulmonary vascular remodeling. Meanwhile, we also observed that hypoxia-induced DRP1 expression depends on ROS generation, especially mitochondrial ROS (mROS). Moreover, the levels of ROS and mROS evoked by hypoxia were regulated by DRP1. Furthermore, we verified the apoptosis suppression of PASMCs under hypoxia due to the interaction between ROS/mROS and DRP1. Our study reveals a novel mechanism of hypoxia-induced pulmonary vascular remodeling, suggesting a new therapeutic strategy which is targeting on the positive feedback of ROS/mROS-DRP1 for the treatment of PAH.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.
authors.forename: Cui
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China.
authors.forename: Mingfei
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Basic Medicine, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Cao
authors.affiliation: Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Daqing, 163319, People's Republic of China. dalingz@yahoo.com.|Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People's Republic of China. dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D034281:Dynamins / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; C519851:Dnm1l protein, rat; D034281:Dynamins
keywords: Chronic hypoxia; Dynamin-related protein-1; Pulmonary artery smooth muscle cells; Reactive oxygen species