BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation

Ecotoxicology and Environmental Safety

Yang Yang¹  Jiarong Guo¹  Huidong Zhang¹  Jingsong Zhao²  Weina Chen³  Chenyang Mi³  Zhongyan Xu³  Wenxin Huang⁴  Rong Wang⁴  Peng Tian⁴ 

[1] Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China;Scientific Research Center, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou 563000, China;West China Fourth Hospital, Sichuan University, Chengdu 610041, China;;Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health &

关键词: Trophoblast cells;    Environmental carcinogens (BPDE);    Iron metabolism;    GPX4;    Ferroptosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Human trophoblast cells play important role in embryo-fetal development. However, trophoblast cells are sensitive to environmental carcinogens. Recently, we have discovered that BPDE inhibits trophoblast cell migration, invasion and proliferation, and also increases trophoblast cell apoptosis. Ferroptosis is a newly identified iron-dependent non-apoptotic programmed cell death. Whether BPDE might induce trophoblast cell ferroptosis is completely unknown. In this work, we have discovered that ferroptosis does occur in BPDE-treated human trophoblast cells. Iron metabolism up-regulates intracellular free Fe2+ level, produces excessive ROS (reactive oxygen species), and accelerates lipid peroxidation. GPX4 efficiently eliminates ROS and inhibits lipid peroxidation. Thus, ferroptosis is well suppressed due to the balance of these two pathways in healthy trophoblast cells. However, BPDE exposure could promote iron metabolism, increase intracellular free Fe2+ level, produce excessive ROS, and result in lipid peroxidation. Meanwhile, BPDE also down-regulates GPX4 expression level by promoting its proteasomal degradation, which eventually produces excessive ROS and induces lipid peroxidation. Thus, BPDE exposure induces trophoblast cell ferroptosis by unbalancing these two pathways, providing new insight in understanding BPDE-induced dysfunctions of human trophoblast cells.

【 授权许可】

Unknown