Iron-bearing nanoparticles trigger human umbilical vein endothelial cells ferroptotic responses by promoting intracellular iron level
Autor: | Xiaomin Xia, Yang Song, Xuying Lv, Erqun Song, Zixuan Liu |
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Rok vydání: | 2021 |
Předmět: |
Programmed cell death
010504 meteorology & atmospheric sciences Iron Health Toxicology and Mutagenesis 010501 environmental sciences Toxicology GPX4 01 natural sciences Umbilical vein Lipid peroxidation chemistry.chemical_compound Human Umbilical Vein Endothelial Cells Ferroptosis Humans 0105 earth and related environmental sciences Glutamate receptor Transporter General Medicine Phospholipid Hydroperoxide Glutathione Peroxidase Pollution Cell biology chemistry mitochondrial fusion Nanoparticles Lipid Peroxidation Intracellular |
Zdroj: | Environmental Pollution. 287:117345 |
ISSN: | 0269-7491 |
Popis: | Iron-bearing nanoparticles (IBNPs) were abundant in particulate matter (PM). Due to their high reactivity, IBNPs were considered hazardous to human health, however, their toxic mode-of-action(s) are highly unclear. Ferroptosis is a novel programmed cell death (PCD) that highly associated with intracellular iron. However, the pro-ferroptotic effect of IBNPs has not been characterized. To this end, we ought to investigate whether and how IBNPs (synthetic γ-Fe2O3 and Fe3O4 NPs were selected as the model compounds) are involved in ferroptosis. We found that human umbilical vein endothelial cells (HUVECs) phagocytized large qualities of γ-Fe2O3 and Fe3O4 NPs, resulting in increased intracellular iron level. We further observed the disrupted cystine/glutamate reverse transporter (System Xc-) and glutathione peroxidase 4 (GPX4) signaling in γ-Fe2O3 and Fe3O4 NPs-challenged HUVECs. γ-Fe2O3 and Fe3O4 NPs could also cause mitochondrial fusion and fission dysregulation, activate lipid peroxidation and iron metabolism-related genes in a P53-dependent manner. Together, the ferroptotic activity of IBNPs should be acknowledged for the risk assessment of PM associated health effects. |
Databáze: | OpenAIRE |
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