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

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. Ferro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peng Tian, Zhongyan Xu, Jiarong Guo, Jingsong Zhao, Rong Wang, Weina Chen, Yang Yang, Wenxin Huang, Chenyang Mi, Huidong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Trophoblast cells Environmental carcinogens (BPDE) Iron metabolism GPX4 Ferroptosis Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/c9afc7bb2d094498ba5a551dea1da78e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c9afc7bb2d094498ba5a551dea1da78e
record_format	dspace
spelling	oai:doaj.org-article:c9afc7bb2d094498ba5a551dea1da78e2021-12-04T04:32:00ZBPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation0147-651310.1016/j.ecoenv.2021.113028https://doaj.org/article/c9afc7bb2d094498ba5a551dea1da78e2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321011404https://doaj.org/toc/0147-6513Human 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.Peng TianZhongyan XuJiarong GuoJingsong ZhaoRong WangWeina ChenYang YangWenxin HuangChenyang MiHuidong ZhangElsevierarticleTrophoblast cellsEnvironmental carcinogens (BPDE)Iron metabolismGPX4FerroptosisEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 228, Iss , Pp 113028- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Trophoblast cells Environmental carcinogens (BPDE) Iron metabolism GPX4 Ferroptosis Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Trophoblast cells Environmental carcinogens (BPDE) Iron metabolism GPX4 Ferroptosis Environmental pollution TD172-193.5 Environmental sciences GE1-350 Peng Tian Zhongyan Xu Jiarong Guo Jingsong Zhao Rong Wang Weina Chen Yang Yang Wenxin Huang Chenyang Mi Huidong Zhang BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation
description	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.
format	article
author	Peng Tian Zhongyan Xu Jiarong Guo Jingsong Zhao Rong Wang Weina Chen Yang Yang Wenxin Huang Chenyang Mi Huidong Zhang
author_facet	Peng Tian Zhongyan Xu Jiarong Guo Jingsong Zhao Rong Wang Weina Chen Yang Yang Wenxin Huang Chenyang Mi Huidong Zhang
author_sort	Peng Tian
title	BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation
title_short	BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation
title_full	BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation
title_fullStr	BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation
title_full_unstemmed	BPDE induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting GPX4 proteasomal degradation
title_sort	bpde induces human trophoblast cell ferroptosis by up-regulating iron metabolism and promoting gpx4 proteasomal degradation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c9afc7bb2d094498ba5a551dea1da78e
work_keys_str_mv	AT pengtian bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT zhongyanxu bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT jiarongguo bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT jingsongzhao bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT rongwang bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT weinachen bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT yangyang bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT wenxinhuang bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT chenyangmi bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation AT huidongzhang bpdeinduceshumantrophoblastcellferroptosisbyupregulatingironmetabolismandpromotinggpx4proteasomaldegradation
_version_	1718373055773802496

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

Ejemplares similares