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  2. "Iron free" zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis

"Iron free" zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis

  • Cell Death Dis. 2020 Mar 13;11(3):183. doi: 10.1038/s41419-020-2384-5.
Changping Zhang 1 Zixuan Liu 2 Yuhao Zhang 1 Liang Ma 1 Erqun Song 2 Yang Song 3
Affiliations

Affiliations

  • 1 Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Food Science, Southwest University, Chongqing, 400715, People's Republic of China.
  • 2 Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China.
  • 3 Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People's Republic of China. ysong@swu.edu.cn.
Abstract

Exposure to nanomaterials (NMs) is an emerging threat to human health, and the understanding of their intracellular behavior and related toxic effects is urgently needed. Ferroptosis is a newly discovered, iron-mediated cell death that is distinctive from Apoptosis or other cell-death pathways. No evidence currently exists for the effect of "iron free" engineered NMs on Ferroptosis. We showed by several approaches that (1) zinc oxide nanoparticles (ZnO NPs)-induced cell death involves ferroptosis; (2) ZnO NPs-triggered Ferroptosis is associated with elevation of Reactive Oxygen Species (ROS) and lipid peroxidation, along with depletion of glutathione (GSH) and downregulation of Glutathione Peroxidase 4 (GPx4); (3) ZnO NPs disrupt intracellular iron homeostasis by orchestrating iron uptake, storage and export; (4) p53 largely participates in ZnO NPs-induced ferroptosis; and (5) ZnO particle remnants and dissolved zinc ion both contribute to Ferroptosis. In conclusion, our data provide a new mechanistic rationale for Ferroptosis as a novel cell-death phenotype induced by engineered NMs.

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