细胞生物学
滋养层
降级(电信)
GPX4
新陈代谢
化学
细胞
生物
生物化学
谷胱甘肽
酶
遗传学
胎盘
胎儿
怀孕
计算机科学
电信
谷胱甘肽过氧化物酶
作者
Peng Tian,Zhongyan Xu,Jiarong Guo,Jingsong Zhao,Rong Wang,Weina Chen,Yang Yang,Weijian Huang,Chenyang Mi,Huidong Zhang
标识
DOI:10.1016/j.ecoenv.2021.113028
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 Fe 2+ 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 Fe 2+ 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. • BPDE exposure induces human trophoblast cell ferroptosis. • BPDE exposure increases intracellular free Fe 2+ level and ROS level. • BPDE promotes GPX4 proteasomal degradation and reduces its protein level. • BPDE produces excessive ROS and induces lipid peroxidation.
科研通智能强力驱动
Strongly Powered by AbleSci AI