Formation of highly stable multinuclear Ag<sub>n</sub>S<sub>n</sub>clusters in zinc fingers disrupts their structure and function

Kluska, Katarzyna; Peris‐Díaz, Manuel David; Płonka, Dawid; Moysa, Alexander; Dadlez, Michał; Deniaud, Aurélien; Bal, Wojciech; Krężel, Artur

doi:10.1039/c9cc09418k

Cited by 25 publications

(52 citation statements)

References 48 publications

(56 reference statements)

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“…Furthermore, very recent data indicate that even apparently non-toxic exposures to AgNPs may impair liver function, by specific inhibition of nuclear receptors, zinc finger effectors of hormonal activity [ 50 ]. Ag(I) ions were recently shown to easily remove Zn(II) ions from zinc fingers, providing molecular background for this process, and indicating that AgNPs may impair zinc-specific pathways as well, even without affecting the bulk cellular zinc [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…AgNPs are made of the Ag(0) core that is oxidized at the surface into Ag(I) ions with subsequent distribution of Ag(I) species throughout the cell mainly in the form of Ag–thiol complexes [ 10 , 11 , 12 , 13 ]. This type of complexation comes as no surprise as Ag has a picomolar or higher affinity for thiols depending on the coordination chemistry offered by the biomolecular ligands [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

Poznański

Sołdacki

Czarkowska–Pączek

et al. 2021

IJMS

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Silver-based materials are widely used in clinical medicine. Furthermore, the usage of silver containing materials and devices is widely recommended and clinically approved. The impact on human health of the increasing use of silver nanoparticles in medical devices remains understudied, even though Ag-containing dressings are known to release silver into the bloodstream. In this study, we detected a widespread and sometimes significant silver accumulation both in healthy and sick liver biopsies, levels being statistically higher in patients with various hepatic pathologies. 28 healthy and 44 cirrhotic liver samples were investigated. The median amount of 0.049 ppm Ag in livers was measured in cirrhotic livers while the median was 0.0016 ppm for healthy livers (a more than 30-fold difference). The mean tissue concentrations of essential metals, Fe and Zn in cirrhotic livers did not differ substantially from healthy livers, while Cu was positively correlated with Ag. The serum levels of gamma-glutamyl transpeptidase (GGTP) was also positively correlated with Ag in cirrhotic livers. The increased Ag accumulation in cirrhotic livers could be a side effect of wide application of silver in clinical settings. As recent studies indicated a significant toxicity of silver nanoparticles for human cells, the above observation could be of high importance for the public health.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

Poznański

Sołdacki

Czarkowska–Pączek

et al. 2021

IJMS

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“…Thus, cellular Zn deprivation, with Zn replacement by Mg and/or specific drugs based on Ag(I) or Au(I) (Kluska et al, 2020 ), might result in a significant slowing down of viral replication, owing to the inhibition of orf7a/BST2 and orf8/BST2 complexes formation. Circumstantial support for this hypothesis comes from the well-known, important role played by Zn in inflammation (Gammoh and Rink, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Virion Stabilization by Zn Binding

Morante

Penna

Rossi

et al. 2020

Front. Mol. Biosci.

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Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

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“…Ag(I) can appear in cuproenzymes, which contain cysteine residues in their active centers and bind to metallothioneins, 28 replace copper in odorant receptors, 33 form stable complexes with cysteine residues in classic zinc finger domains and zinc fingers of soluble nuclear hormone receptors. 40 As a result, the enzymatic activities of cuproenzymes are impaired, while copper- and zinc-dependent regulatory factors lose their normal ability for specific interaction. Thus, Ag(I) causes a dysregulation of copper homeostasis and disbalance in the regulation of hundreds of genes, which may finally result in neurodegeneration and tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Size-Dependent Bioactivity of Silver Nanoparticles: Antibacterial Properties, Influence on Copper Status in Mice, and Whole-Body Turnover

Skomorokhova¹,

Sankova²,

Orlov³

et al. 2020

NSA

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The ability of silver nanoparticles (AgNPs) of different sizes to influence copper metabolism in mice is assessed. Materials and Methods: AgNPs with diameters of 10, 20, and 75 nm were fabricated through a chemical reduction of silver nitrate and characterized by UV/Vis spectrometry, transmission and scanning electronic microscopy, and laser diffractometry. To test their bioactivity, Escherichia coli cells, cultured A549 cells, and C57Bl/6 mice were used. The antibacterial activity of AgNPs was determined by inhibition of colony-forming ability, and cytotoxicity was tested using the MTT test (viability, %). Ceruloplasmin (Cp, the major mammalian extracellular copper-containing protein) concentration and enzymatic activity were measured using gel-assay analyses and WB, respectively. In vitro binding of AgNPs with serum proteins was monitored with UV/Vis spectroscopy. Metal concentrations were measured using atomic absorption spectrometry. Results: The smallest AgNPs displayed the largest dose-and time-dependent antibacterial activity. All nanoparticles inhibited the metabolic activity of A549 cells in accordance with dose and time, but no correlation between cytotoxicity and nanoparticle size was found. Nanosilver was not uniformly distributed through the body of mice intraperitoneally treated with low AgNP concentrations. It was predominantly accumulated in liver. There, nanosilver was included in ceruloplasmin, and Ag-ceruloplasmin with low oxidase activity level was formed. Larger nanoparticles more effectively interfered with the copper metabolism of mice. Large AgNPs quickly induced a drop of blood serum oxidase activity to practically zero, but after cancellation of AgNP treatment, the activity was rapidly restored. A major fraction of the nanosilver was excreted in the bile with Cp. Nanosilver was bound by alpha-2-macroglobulin in vitro and in vivo, but silver did not substitute for the copper atoms of Cp in vitro. Conclusion:The data showed that even at low concentrations, AgNPs influence murine copper metabolism in size-dependent manner. This property negatively correlated with the antibacterial activity of AgNPs.

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Formation of highly stable multinuclear Ag_nS_nclusters in zinc fingers disrupts their structure and function

Abstract: Silver (Ag(i)) binding to consensus zinc fingers (ZFs) causes Zn(ii) release inducing a gradual disruption of the hydrophobic core, followed by an overall conformational change and formation of highly stable AgnSn clusters.

Cited by 25 publications

References 48 publications

Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

SARS-CoV-2 Virion Stabilization by Zn Binding

Size-Dependent Bioactivity of Silver Nanoparticles: Antibacterial Properties, Influence on Copper Status in Mice, and Whole-Body Turnover

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Formation of highly stable multinuclear AgnSnclusters in zinc fingers disrupts their structure and function

Abstract: Silver (Ag(i)) binding to consensus zinc fingers (ZFs) causes Zn(ii) release inducing a gradual disruption of the hydrophobic core, followed by an overall conformational change and formation of highly stable AgnSn clusters.

Cited by 25 publications

References 48 publications

Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper

SARS-CoV-2 Virion Stabilization by Zn Binding

Size-Dependent Bioactivity of Silver Nanoparticles: Antibacterial Properties, Influence on Copper Status in Mice, and Whole-Body Turnover

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Formation of highly stable multinuclear Ag_nS_nclusters in zinc fingers disrupts their structure and function