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BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation.
- Source :
- Ecotoxicology & Environmental Safety; Dec2021, Vol. 228, pN.PAG-N.PAG, 1p
- Publication Year :
- 2021
-
Abstract
- 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<superscript>2+</superscript> 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<superscript>2+</superscript> 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<superscript>2+</superscript> level and ROS level. • BPDE promotes GPX4 proteasomal degradation and reduces its protein level. • BPDE produces excessive ROS and induces lipid peroxidation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01476513
- Volume :
- 228
- Database :
- Supplemental Index
- Journal :
- Ecotoxicology & Environmental Safety
- Publication Type :
- Academic Journal
- Accession number :
- 154013385
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2021.113028