title: Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells.
abstract: The role of progesterone on the cardiovascular system is controversial. Our present research is to specify the effect of progesterone on arterial endothelial cells in response to oxidative stress. Our result showed that H2O2 (150 μM and 300 μM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2O2-treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2O2. However, progesterone absolutely abolished the antioxidant response through increasing ROS level, inhibiting the activity of Glutathione peroxidase (GPx), decreasing GSH level and reducing expression of GClC and GCLM. In our study, H2O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2O2-induced NO production. Progesterone increased H2O2-induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2O2 of culture medium pretreated by progesterone combined with H2O2 or progesterone alone. GSH also inhibited expression of HIFα and eNOS, and abolished NO synthesis. Collectively, our study demonstrated for the first time that progesterone inhibited cellular antioxidant effect and increased oxidative stress, promoted NO production of arterial endothelial cells, which may be due to the increasing H2O2 concentration and amplified oxidative stress signal.
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China; Central Laboratory, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Yuan
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Fan
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Yang
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Gao
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China. Electronic address: biolabs@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Maternity Department, Shaanxi Provincial People's Hospital, Xi'an 710068, China. Electronic address: wangyaqin49@163.com.
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Central Laboratory, Shaanxi Provincial People's Hospital, Xi'an 710068, China. Electronic address: hjj6562@163.com.
authors.forename: Hu
authors.initials: H
authors.lastname: Jun
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D011374:Progesterone; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D005978:Glutathione
keywords: H(2)O(2); NO; Progesterone; ROS; Vascular