BMC cardiovascular disorders · 2023
Homocysteine induces ferroptosis in endothelial cells through the systemXc-/GPX4 signaling pathway.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shi Jiahao, Chen Di, Wang Zilin, Li Shaolin, Zhang Shuying
Аннотация
OBJECTIVES: To investigate whether ferroptosis is involved in HCY-induced endothelial injury and the possible mechanism of HCY-induced ferroptosis.
METHODS: EA. hy926 cells were cultured in vitro. Cells were intervened using HCY and Fer-1. The cells were divided into Control groups, HCY (4 mM), HCY (8 mM), HCY + Fer-1 (4 mM HCY + 0.5/2.5/5 µM Fer-1). CCK-8 assay was used to detect cell viability; Flow Cytometry was used to detect cellular Lip-ROS, TBA and Microplate assay was used to detect MDA&GSH, Western blot was used to detect the expression of ferroptosis-related proteins GPX4 and SLC7A11.
RESULTS: HCY can inhibited the proliferation of EA. hy926 cells in a time- and concentration-dependent manner; Fer-1 inhibits HCY-induced ferroptosis in EA.hy926 cells in a concentration-dependent manner; Compared with the control group, the cell viability and GSH content in the HCY group was significantly decreased (p < 0.05), and the Lip-ROS and MDA were significantly increased (p < 0.05); After co-culture of HCY and Fer-1, compared with the HCY (4 mM) group, the cell viability and GSH content in the co-culture group were significantly increased (p < 0.05), and the Lip-ROS and MDA were significantly decreased (p < 0.05) in a concentration-dependent manner; Western blotting results showed that the protein expression levels of ferroptosis-related proteins GPX4 and SLC7A11 in each experimental were significantly decreased after HCY treatment (p < 0.05), and Fer-1 could significantly reverse this effect.
CONCLUSIONS: (1) HCY can induce ferroptosis in vascular endothelial cells. (2) HCY may induce vascular endothelial cell ferroptosis through the system Xc-GSH-GPX4 signaling pathway.
METHODS: EA. hy926 cells were cultured in vitro. Cells were intervened using HCY and Fer-1. The cells were divided into Control groups, HCY (4 mM), HCY (8 mM), HCY + Fer-1 (4 mM HCY + 0.5/2.5/5 µM Fer-1). CCK-8 assay was used to detect cell viability; Flow Cytometry was used to detect cellular Lip-ROS, TBA and Microplate assay was used to detect MDA&GSH, Western blot was used to detect the expression of ferroptosis-related proteins GPX4 and SLC7A11.
RESULTS: HCY can inhibited the proliferation of EA. hy926 cells in a time- and concentration-dependent manner; Fer-1 inhibits HCY-induced ferroptosis in EA.hy926 cells in a concentration-dependent manner; Compared with the control group, the cell viability and GSH content in the HCY group was significantly decreased (p < 0.05), and the Lip-ROS and MDA were significantly increased (p < 0.05); After co-culture of HCY and Fer-1, compared with the HCY (4 mM) group, the cell viability and GSH content in the co-culture group were significantly increased (p < 0.05), and the Lip-ROS and MDA were significantly decreased (p < 0.05) in a concentration-dependent manner; Western blotting results showed that the protein expression levels of ferroptosis-related proteins GPX4 and SLC7A11 in each experimental were significantly decreased after HCY treatment (p < 0.05), and Fer-1 could significantly reverse this effect.
CONCLUSIONS: (1) HCY can induce ferroptosis in vascular endothelial cells. (2) HCY may induce vascular endothelial cell ferroptosis through the system Xc-GSH-GPX4 signaling pathway.