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

Zhang, Changping; Liu, Zixuan; Zhang, Yuhao; Ma, Liang; Song, Erqun; Song, Yang

doi:10.1038/s41419-020-2384-5

Cited by 82 publications

(62 citation statements)

References 57 publications

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“…For example, zinc can enhance mitochondrial ROS generation [ 7 ], induce lipid peroxidation and trigger ferroptosis via the phosphorylation of xCT [ 8 ]. Consistent with our results, “iron-free” zinc oxide nanoparticles also trigger ferroptosis via increasing ROS, lipid oxidation, and depleting glutathione [ 9 ]. While it is still possible that zinc affect ferroptosis through regulating iron levels, multiple independent studies on the essential role of zinc in ferroptosis may prompt re-examinations of the central role of iron in ferroptosis as implied in the name of this form of regulated cell death.…”

Section: Unexpected Role Of Zinc and Zip7 In Ferroptosissupporting

confidence: 90%

Unexpected zinc dependency of ferroptosis: what is in a name?

Chen¹,

Chi²

2021

Oncotarget

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Section: Unexpected Role Of Zinc and Zip7 In Ferroptosissupporting

confidence: 90%

Unexpected zinc dependency of ferroptosis: what is in a name?

Chen¹,

Chi²

2021

Oncotarget

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“…One of critical ferroptosis hallmarks is lipid peroxidation ( 20 , 21 , 45 ). The interplay between lipids and intracellular ROS represents a fundamental process in ferroptosis ( 20 , 46 , 47 ). Evidence from our recently published study has revealed that intracellular ROS production is substantially elevated in 661W photoreceptor cells at 6 h after exposure to 5-μM atRAL ( 19 ).…”

Section: Resultsmentioning

confidence: 99%

Ferroptosis drives photoreceptor degeneration in mice with defects in all-trans-retinal clearance

Chen

Wang

et al. 2021

Journal of Biological Chemistry

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The death of photoreceptor cells in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1) is closely associated with disruption in all- trans -retinal (atRAL) clearance in neural retina. In this study, we reveal that the overload of atRAL leads to photoreceptor degeneration through activating ferroptosis, a nonapoptotic form of cell death. Ferroptosis of photoreceptor cells induced by atRAL resulted from increased ferrous ion (Fe 2+ ), elevated ACSL4 expression, system Xc − inhibition, and mitochondrial destruction. Fe 2+ overload, tripeptide glutathione (GSH) depletion, and damaged mitochondria in photoreceptor cells exposed to atRAL provoked reactive oxygen species (ROS) production, which, together with ACSL4 activation, promoted lipid peroxidation and thereby evoked ferroptotic cell death. Moreover, exposure of photoreceptor cells to atRAL activated COX2, a well-accepted biomarker for ferroptosis onset. In addition to GSH supplement, inhibiting either Fe 2+ by deferoxamine mesylate salt (DFO) or lipid peroxidation with ferrostatin-1 (Fer-1) protected photoreceptor cells from ferroptosis caused by atRAL. Abca4 −/− Rdh8 −/− mice exhibiting defects in atRAL clearance is an animal model for dry AMD and STGD1. We observed that ferroptosis was indeed present in neural retina of Abca4 −/− Rdh8 −/− mice after light exposure. More importantly, photoreceptor atrophy and ferroptosis in light-exposed Abca4 −/− Rdh8 −/− mice were effectively alleviated by intraperitoneally injected Fer-1, a selective inhibitor of ferroptosis. Our study suggests that ferroptosis is one of the important pathways of photoreceptor cell death in retinopathies arising from excess atRAL accumulation and should be pursued as a novel target for protection against dry AMD and STGD1.

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“…The mechanism of biotoxicity of nanomaterials is multifaceted and unclear. Among them, the oxidative stress caused by the production of a large amount of ROS is considered to be one of the possible mechanisms of its toxic effects 47 . In the physiological state, the expression level of ROS keeps dynamic balance.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of mesoporous silica modified by amino and carboxyl groups on vascular endothelial cells

Zhao

Zhang

et al. 2021

Environmental Toxicology

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Mesoporous silica is widely used because of its unique and excellent properties, especially it can be used as a drug carrier and gene carrier in the biomedical field. After the mesoporous silica is put into clinical use, it is more likely to be exposed in human body. Therefore, the effect of mesoporous silica on human body cannot be ignored. The injury of vascular endothelial cells is a prerequisite for the occurrence of many cardiovascular diseases. As a drug and gene carrier, mesoporous silica increases its contact with vascular endothelial cells, so its toxic effect on cardiovascular system cannot be ignored. In this study, amino (NH2) and carboxyl (COOH) were modified on mesoporous silica SBA‐15 by post‐grafting. The results showed that it still maintained the one‐dimensional hexagonal mesoporous structure of SBA‐15 and had typical mesoporous structure. Then human umbilical vein endothelial cells (HUVECs) were infected with SBA‐15, NH2‐SBA‐15, and COOH‐SBA‐15. The results showed that the functionalized mesoporous silica SBA‐15 had cytotoxicity to HUVECs and damaged the cell membrane, but compared with the unmodified mesoporous silica SBA‐15 the cytotoxicity of functionalized mesoporous silica SBA‐15 was lower and the toxicity of carboxyl modified group was the lowest. By comparing the cell inhibition rate and the expression level of lactate dehydrogenate and reactive oxygen species induced by the three materials, oxidative damage and cell membrane damage may be two mechanisms of cytotoxicity. Mesoporous silica SBA‐15 has an effect on cardiovascular system by inducing the high expression of nitric oxide, intercellular adhesive molecule‐1 and vascular cell adhesive molecule‐1 in HUVECs. In summary, our results show that mesoporous silica is toxic to vascular endothelial cells.

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

Cited by 82 publications

References 57 publications

Unexpected zinc dependency of ferroptosis: what is in a name?

Unexpected zinc dependency of ferroptosis: what is in a name?

Ferroptosis drives photoreceptor degeneration in mice with defects in all-trans-retinal clearance

Cytotoxicity of mesoporous silica modified by amino and carboxyl groups on vascular endothelial cells

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