Se improves GPX4 expression and SOD activity to alleviate heat-stress-induced ferroptosis-like death in goat mammary epithelial cells

Abstract

Selenium (Se) is a vital element of life, which has an important impact on the growth, development, production performance and stress-tolerance of animals. However, it is not entirely clear that how exactly Se works during these processes. Herein, we investigate the role of Se in regulating the functions of goat mammary epithelial cells (GMECs) under heat-stress condition. We found that heat stress caused ferroptosis-like death in GMECs, manifested by a robust increase in iron ion concentration, reactive oxygen species (ROS) and cell death ratio, and a decrease in the activity of superoxide dismutase (SOD) and expression level of glutathione peroxidases 4 (GPX4). Se incubation had no obvious effect on GMEC viability, but alleviated heat-stress-induced ferroptosis-like cell death and improved GPX4 expression and SOD activity in a dose-dependent manner. Also, we found that overexpression of GPX4 could improve the activity of SOD. And Se incubation inhibited activation of mTOR signaling in heat-stress-induced GMECs, which could be eliminated by the mTOR activator MHY1485, and treatment with mTOR inhibitor AY-22989 had the same effect as Se. In conclusion, Se improves GPX4 expression and SOD activity and inhibits the activation of mTOR to alleviate heat-stress-induced ferroptosis-like death in GMECs, which may be a protective agent for heat stress in goats.

Keywords

• ferroptosis
• selenium
• heat stress
• gpx4
• sod