Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells. Issue 155 (January 2016) - Yuan, Xiao-Hua
Highlights: Our research was focus on the effect of progesterone on the arterial endothelial cells. Progesterone inhibited cellular antioxidant effect and increased oxidative stress. Progesterone promoted NO production in arterial endothelial cells. Progesterone promoted NO production through increasing H2 O2 concentration. 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 H2 O2 (150 μM and 300 μM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2 O2 -treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2 O2 . 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, H2 O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2 O2 -induced NO production. Progesterone increased H2 O2 -induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2 O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2 O2 of culture medium pretreated by progesterone combined with H2 O2 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 H2 O2 concentration and amplified oxidative stress signal.