Copper(II)-binding equilibria in human blood

Kirsipuu, Tiina; Zadorožnaja, Anna; Smirnova, Julia; Friedemann, Merlin; Plitz, Thomas; Tõugu, Vello; Palumaa, Peep

doi:10.1038/s41598-020-62560-4

Cited by 71 publications

(75 citation statements)

References 47 publications

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“…81 Moreover, Kirsipuu et al have persuasively shown that copper is bound to Cp in a nonexchangeable form. 83 A possible source of inconsistency is the use of different Cp samples. The work of Liu et al, 82 used a commercial sample of Cp with no absorption at 610 nm, which is a necessary feature of holo-Cp.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Furthermore, we observed a significant increase in the 40-80 kDa Cu fraction matching with the HSA standard. Similar to Zn, HSA is also reported as a minor Cu carrier [70].…”

Section: Total Quantification and Sec-separation Of Metal Species In Serum And Csf Samplesmentioning

confidence: 88%

Simultaneous Quantification and Speciation of Trace Metals in Paired Serum and CSF Samples by Size Exclusion Chromatography–Inductively Coupled Plasma–Dynamic Reaction Cell–Mass Spectrometry (SEC-DRC-ICP-MS)

Michalke

Berthele

Venkataramani

2021

IJMS

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Background: Transition metals play a crucial role in brain metabolism: since they exist in different oxidation states they are involved in ROS generation, but they are also co-factors of enzymes in cellular energy metabolism or oxidative defense. Methods: Paired serum and cerebrospinal fluid (CSF) samples were analyzed for iron, zinc, copper and manganese as well as for speciation using SEC-ICP-DRC-MS. Brain extracts from Mn-exposed rats were additionally analyzed with SEC-ICP-DRC-MS. Results: The concentration patterns of transition metal size fractions were correlated between serum and CSF: Total element concentrations were significantly lower in CSF. Fe-ferritin was decreased in CSF whereas a LMW Fe fraction was relatively increased. The 400–600 kDa Zn fraction and the Cu-ceruloplasmin fraction were decreased in CSF, by contrast the 40–80 kDa fraction, containing Cu- and Zn-albumin, relatively increased. For manganese, the α-2-macroglobulin fraction showed significantly lower concentration in CSF, whereas the citrate Mn fraction was enriched. Results from the rat brain extracts supported the findings from human paired serum and CSF samples. Conclusions: Transition metals are strictly controlled at neural barriers (NB) of neurologic healthy patients. High molecular weight species are down-concentrated along NB, however, the Mn-citrate fraction seems to be less controlled, which may be problematic under environmental load.

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“…Spiking real serum samples was not an option for validation/recovery of extractable Cu since the serum proteins were also binding the Cu. 35,36 To determine the precision of the method, a stock amount of fetal serum was spiked with 0.16 mM Cu and analyzed as 125 repeat samples (B15 h of continuous analysis time). Over the span of 125 samples, there was a 2.0% RSD for the extractable Cu and 4.2% RSD for the bound Cu.…”

Section: Methods Developmentmentioning

confidence: 99%