The following is a summary of “Homocysteine induces ferroptosis in endothelial cells through the systemXc−/GPX4 signaling pathway,” published in the July 2023 issue of Cardiology by Shi, et al.
In the retrospective study, researchers aimed to determine if ferroptosis is the reason for HCY-induced endothelial injury and to understand the HCY-induced ferroptosis mechanism.
The study, cultured EA.hy926 cells were used to intervene with different substances, HCY and Fer-1. Further, these cells were categorized into two groups HCY (4 mM), HCY (8 mM), HCY + Fer-1 (4 mM HCY + 0.5/2.5/5 µM Fer-1). To assess the effects of these treatments, they used various techniques like CCK-8 assay to measure cell viability, Flow cytometry for cellular Lip-ROS, Microplate assay to detect MDA and GSH, Western blot to measure the levels of ferroptosis-related proteins, GPX4 and SLC7A11.
HCY restrained EA. hy926 cells’ growth, depending on time and the concentration used. In EA.hy926 cells, Fer-1 hindered the HCY-induced ferroptosis and its effectiveness on its concentration. In comparison, in the HCY group, the cell viability and GSH content dropped (p < 0.05), and the Lip-ROS and MDA boosted (p < 0.05). After HCY and Fer-1 were co-cultured, the co-culture group compared with the HCY (4 mM) group; the co-culture group’s cell viability and GSH content were significantly high(p < 0.05). However, Lip-ROS and MDA were low (p < 0.05) in a concentration-dependent manner. Western blotting demonstrated that expression levels of ferroptosis-related proteins GPX4 and SLC7A11 were significantly reduced after HCY treatment (p < 0.05). However, Fer-1 was able to reverse this effect and increase its expression levels.
The study concluded that Homocysteine induces ferroptosis in vascular endothelial cells via the systemXc–GSH-GPX4 signaling pathway.
Source: bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-023-03342-4
