Copper (Cu) is a vital mineral essential for many biological processes. The vast majority of all Cu in healthy humans is associated with enzyme prosthetic groups or bound to proteins. Cu homeostasis ...is tightly regulated through a complex system of Cu transporters and chaperone proteins. Excess or toxicity of Cu, which is associated with the pathogenesis of hepatic disorder, neurodegenerative changes and other disease conditions, can occur when Cu homeostasis is disrupted. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced cellular toxicity. Recently, altered cellular events, including lipid metabolism, gene expression, alpha-synuclein aggregation, activation of acidic sphingomyelinase and release of ceramide, and temporal and spatial distribution of Cu in hepatocytes, as well as Cu-protein interaction in the nerve system, have been suggested to play a role in Cu toxicity. However, whether these changes are independent of, or secondary to, an altered cellular redox state of Cu remain to be elucidated.
Laccases are part of the family of multicopper oxidases (MCOs), which couple the oxidation of substrates to the four electron reduction of O₂to H₂O. MCOs contain a minimum of four Cu’s divided into ...Type 1 (T1), Type 2 (T2), and binuclear Type 3 (T3) Cu sites that are distinguished based on unique spectroscopic features. Substrate oxidation occurs near the T1, and electrons are transferred approximately 13 Å through the protein via the Cys-His pathway to the T2/T3 trinuclear copper cluster (TNC), where dioxygen reduction occurs. This review outlines the electron transfer (ET) process in laccases, and the mechanism of O₂reduction as elucidated through spectroscopic, kinetic, and computational data. Marcus theory is used to describe the relevant factors which impact ET rates including the driving force, reorganization energy, and electronic coupling matrix element. Then, the mechanism of O₂reaction is detailed with particular focus on the intermediates formed during the two 2e⁻reduction steps. The first 2e⁻step forms the peroxide intermediate, followed by the second 2e⁻step to form the native intermediate, which has been shown to be the catalytically relevant fully oxidized form of the enzyme.
Copper signalling: causes and consequences Kardos, Julianna; Héja, László; Simon, Ágnes ...
Cell communication and signaling,
10/2018, Volume:
16, Issue:
1
Journal Article
Peer reviewed
Open access
Copper-containing enzymes perform fundamental functions by activating dioxygen (O
) and therefore allowing chemical energy-transfer for aerobic metabolism. The copper-dependence of O
transport, ...metabolism and production of signalling molecules are supported by molecular systems that regulate and preserve tightly-bound static and weakly-bound dynamic cellular copper pools. Disruption of the reducing intracellular environment, characterized by glutathione shortage and ambient Cu(II) abundance drives oxidative stress and interferes with the bidirectional, copper-dependent communication between neurons and astrocytes, eventually leading to various brain disease forms. A deeper understanding of of the regulatory effects of copper on neuro-glia coupling via polyamine metabolism may reveal novel copper signalling functions and new directions for therapeutic intervention in brain disorders associated with aberrant copper metabolism.
Copper oxide nanomaterials (CuO NMs) are exploited in a diverse array of products including antimicrobials, inks, cosmetics, textiles and food contact materials. There is therefore a need to assess ...the toxicity of CuO NMs to the gastrointestinal (GI) tract since exposure could occur via direct oral ingestion, mucocillary clearance (following inhalation) or hand to mouth contact.
Undifferentiated Caco-2 intestinal cells were exposed to CuO NMs (10 nm) at concentrations ranging from 0.37 to 78.13 μg/cm
Cu (equivalent to 1.95 to 250 μg/ml) and cell viability assessed 24 h post exposure using the alamar blue assay. The benchmark dose (BMD 20), determined using PROAST software, was identified as 4.44 μg/cm
for CuO NMs, and 4.25 μg/cm
for copper sulphate (CuSO
), which informed the selection of concentrations for further studies. The differentiation status of cells and the impact of CuO NMs and CuSO
on the integrity of the differentiated Caco-2 cell monolayer were assessed by measurement of trans-epithelial electrical resistance (TEER), staining for Zonula occludens-1 (ZO-1) and imaging of cell morphology using scanning electron microscopy (SEM). The impact of CuO NMs and CuSO
on the viability of differentiated cells was performed via assessment of cell number (DAPI staining), and visualisation of cell morphology (light microscopy). Interleukin-8 (IL-8) production by undifferentiated and differentiated Caco-2 cells following exposure to CuO NMs and CuSO
was determined using an ELISA. The copper concentration in the cell lysate, apical and basolateral compartments were measured with Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES) and used to calculate the apparent permeability coefficient (P
); a measure of barrier permeability to CuO NMs. For all experiments, CuSO
was used as an ionic control.
CuO NMs and CuSO
caused a concentration dependent decrease in cell viability in undifferentiated cells. CuO NMs and CuSO
translocated across the differentiated Caco-2 cell monolayer. CuO NM mediated IL-8 production was over 2-fold higher in undifferentiated cells. A reduction in cell viability in differentiated cells was not responsible for the lower level of cytokine production observed. Both CuO NMs and CuSO
decreased TEER values to a similar extent, and caused tight junction dysfunction (ZO-1 staining), suggesting that barrier integrity was disrupted.
CuO NMs and CuSO
stimulated IL-8 production by Caco-2 cells, decreased barrier integrity and thereby increased the P
and translocation of Cu. There was no significant enhancement in potency of the CuO NMs compared to CuSO
. Differentiated Caco-2 cells were identified as a powerful model to assess the impacts of ingested NMs on the GI tract.
A copper-based catalytic technique for the regioselective ortho CH cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of ...vinylarene derivatives. A copper-catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction.
The spread of bacterial infections often occurs through indirect contact with infected individuals. Thus, surfaces with antimicrobial properties have gained prominence in healthcare and public ...spaces. Testing standards exist for assessing the antibacterial effectiveness of these materials, but they do not consider surface properties, particularly surface wettability during microbiological tests. An experiment was conducted to modify copper and its alloys’ surfaces through chemical treatment, altering contact angles. The results revealed that contact angles significantly influence the contact area between droplets and test surfaces, as well as the evaporation time of droplets. These factors can ultimately impact the results of antimicrobial efficacy tests.
Super dosing copper (Cu) has long been used as an alternative to antibiotic growth-promoters in broiler chickens' diet to improve gut health. This study was designed to compare nutritional and ...growth-promoting levels of Cu hydroxychloride (CH) with CuSO
on gut health bio-markers and liver mineral profile of broiler chickens. Ross 308 chicks (n = 864) were randomly assigned to eight treatments, as basal diet containing no supplemental Cu; the basal diet with 15 or 200 mg/kg Cu as CuSO
; or 15, 50, 100, 150 or 200 mg/kg Cu from CH. The highest liver Cu content was observed in birds fed the diets with 200 mg/kg CuSO
(P < 0.01). Serum FITC-d concentration as the leaky gut marker, and liver malondialdehyde concentration were not affected. Copper level or source had no effect on cecal short chain fatty acid and the mRNA expression of five jejunal genes involved in gut integrity. Negative linear responses of Cu were observed on Lactobacillus (P = 0.032), Bacteroides (P = 0.033), and Enterobacteriaceae (P = 0.028) counts. The jejunal villus height increased in birds fed CH at 200 and 100 mg/kg (P < 0.05). Increasing Cu levels, linearly and quadratically (P < 0.001), increased Cu excretion.
From the interplay of STM imaging and DFT calculations we have investigated the isomerization of an alkene molecule on Cu(110) under ultrahigh vacuum conditions. We show that the on-surface ...cis-transisomerization could efficiently occur well below room temperature, in which the copper surface is speculated to play a key role.
Copper ions are needed for several hallmarks of cancer. However, the involved pathways, mechanisms, and copper-binding proteins are mostly unknown. We recently found that cytoplasmic Antioxidant 1 ...copper chaperone (Atox1), which is up-regulated in breast cancer, is localized at the lamellipodia edges of aggressive breast cancer cells. To reveal molecular insights into a putative role in cell migration, we here investigated breast cancer cell (MDA-MB-231) migration by video microscopy as a function of Atox1. Tracking of hundreds of individual cells (per condition) over a 9-h time series revealed that cell migration velocity and directionality are significantly reduced upon Atox1 silencing in the cells. Because silencing of the copper transporter ATP7A also reduced cell migration, these proteins appear to be on the same pathway, suggesting that their well-known copper transport activity is involved. In-cell proximity ligation assays demonstrated that Atox1, ATP7A, and the proenzyme of lysyl oxidase (LOX; copper-loaded via ATP7A) are all in close proximity and that LOX activity is reduced upon Atox1 silencing in the cells. Since LOX is an established player in cancer cell migration, our results imply that Atox1 mediates breast cancer cell migration via coordinated copper transport in the ATP7A-LOX axis. Because individual cell migration is an early step in breast cancer metastasis, Atox1 levels in tumor cells may be a predictive measure of metastasis potential and serve as a biomarker for copper depletion therapy.
In this paper, a novel photoelectrochemical sensor based on doped quantum dots (QDs) without enzymes was designed for direct detection of H 2 O 2 and indirect detection of glucose. First, the ...fabrication processes of doped QDs based sensors were described. Second, doped QDs based sensors were tested under different applied potentials and light sources to optimize the measurement conditions. Third, the sensing properties of doped QDs on H 2 O 2 were given, which have been compared with the results from other QDs. Cu doped QDs showed better sensing properties. Finally, detection of glucose was achieved by doped QDs based photoelectrochemical sensors. From the experimental results, it can be concluded that the doped QDs based sensors designed by us can be used to detect H 2 O 2 and glucose.
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