Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Environ Pollut. 2021 Oct 15;287:117345. doi: 10.1016/j.envpol.2021.117345. Epub 2021 May 11.
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-FeO and FeO 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-FeO and FeO NPs, resulting in increased intracellular iron level. We further observed the disrupted cystine/glutamate reverse transporter (System X) and glutathione peroxidase 4 (GPX4) signaling in γ-FeO and FeO NPs-challenged HUVECs. γ-FeO and FeO 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.
铁纳米颗粒（IBNPs）在颗粒物（PM）中含量丰富。由于其高反应性，IBNPs 被认为对人类健康有害，但它们的毒性作用机制尚不清楚。铁死亡是一种新型的程序性细胞死亡（PCD），与细胞内铁高度相关。然而，IBNPs 的促铁死亡作用尚未得到表征。为此，我们应该研究 IBNPs（选择合成的γ-FeO 和 FeO NPs 作为模型化合物）是否以及如何参与铁死亡。我们发现人脐静脉内皮细胞（HUVECs）吞噬大量的γ-FeO 和 FeO NPs，导致细胞内铁水平升高。我们进一步观察到在 γ-FeO 和 FeO NPs 刺激的 HUVECs 中胱氨酸/谷氨酸反向转运体（System X）和谷胱甘肽过氧化物酶 4（GPX4）信号被破坏。γ-FeO 和 FeO NPs 还可以通过依赖 P53 的方式引起线粒体融合和裂变失调，激活脂质过氧化和铁代谢相关基因。总之，应该认识到 IBNPs 的铁死亡活性对于评估与 PM 相关的健康影响的风险。
