Liu Lu, Wang Manjiang, Gong Ning, Tian Peng, Deng Hongxia
College of Chemistry & Pharmacy, Northwest Agricultural & Forestry University, Yangling, People's Republic of China.
Fuping County Animal Epidemic Prevention Control Center, Xianyang, People's Republic of China.
Anim Cells Syst (Seoul). 2021 Oct 17;25(5):283-295. doi: 10.1080/19768354.2021.1988704. eCollection 2021.
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.
硒（Se）是生命必需的元素，对动物的生长、发育、生产性能和抗逆性有重要影响。然而，硒在这些过程中具体是如何发挥作用的尚不完全清楚。在此，我们研究了硒在热应激条件下对山羊乳腺上皮细胞（GMECs）功能的调节作用。我们发现热应激导致GMECs发生铁死亡样死亡，表现为铁离子浓度、活性氧（ROS）和细胞死亡率显著增加，超氧化物歧化酶（SOD）活性和谷胱甘肽过氧化物酶4（GPX4）表达水平降低。硒孵育对GMECs的活力没有明显影响，但能减轻热应激诱导的铁死亡样细胞死亡，并以剂量依赖的方式提高GPX4表达和SOD活性。此外，我们发现过表达GPX4可以提高SOD的活性。并且硒孵育抑制了热应激诱导的GMECs中mTOR信号通路的激活，mTOR激活剂MHY1485可消除这种抑制作用，而用mTOR抑制剂AY - 22989处理具有与硒相同的效果。总之，硒通过提高GPX4表达和SOD活性以及抑制mTOR的激活来减轻热应激诱导的GMECs铁死亡样死亡，这可能是山羊热应激的一种保护剂。
