title: Antioxidant mechanism of Rutin on hypoxia-induced pulmonary arterial cell proliferation.
abstract: Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Nangang District, Harbin 150081, China. liqian@ems.hrbmu.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Nangang District, Harbin 150081, China. yingzi1314179@126.com.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Bio-pharmaceutical Key Laboratory of Harbin, Harbin Medical University, Harbin 150081, China. mmarine510704@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Mao
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Nangang District, Harbin 150081, China. m15645109321@163.com.
authors.forename: Jinying
authors.initials: J
authors.lastname: Lv
authors.affiliation: Bio-pharmaceutical Key Laboratory of Harbin, Harbin Medical University, Harbin 150081, China. muzqian@sina.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Bio-pharmaceutical Key Laboratory of Harbin, Harbin Medical University, Harbin 150081, China. yw198269@163.com.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Nangang District, Harbin 150081, China. fengyucaihong78@sohu.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University-Daqing, Daqing 163319, China. xzheng2001@163.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D012431:Rutin; D019255:NADPH Oxidases