The irradiation damage behaviors of single crystal (SC), coarse-grained (CG), and nanograined (NG) copper (Cu) films were investigated under Helium (He) ion implantation at 450 degree C with ...different ion fluences. In irradiated SC films, plenty of cavities are nucleated, and some of them preferentially formed on growth defects or dislocation lines. In the irradiated CG Cu, cavities formed both in grain interior and along grain boundaries; obvious void-denuded zones can be identified near grain boundaries. In contrast, irradiation-induced cavities in NG Cu were observed mainly gathering along grain boundaries with much less cavities in the grain interiors. The grains in irradiated NG Cu are significantly coarsened. The number density and average radius of cavities in NG Cu was smaller than that in irradiated SC Cu and CG Cu. These experiments indicate that grain boundaries are efficient sinks for irradiation-induced vacancies and highlight the important role of reducing grain size in suppressing radiation-induced void swelling.
Abnormal cellular copper levels have been clearly implicated in genetic diseases, cancer, and neurodegeneration. Ctr1, a high-affinity copper transporter, is a homotrimeric integral membrane protein ...that provides the main route for cellular copper uptake. Together with a sophisticated copper transport system, Ctr1 regulates Cu(I) metabolism in eukaryotes. Despite its pivotal role in normal cell function, the molecular mechanism of copper uptake and transport via Ctr1 remains elusive. In this study, electron paramagnetic resonance (EPR), UV-visible spectroscopy, and all-atom simulations were employed to explore Cu(I) binding to full-length human Ctr1 (hCtr1), thereby elucidating how metal binding at multiple distinct sites affects the hCtr1 conformational dynamics. We demonstrate that each hCtr1 monomer binds up to five Cu(I) ions and that progressive Cu(I) binding triggers a marked structural rearrangement in the hCtr1 C-terminal region. The observed Cu(I)-induced conformational remodeling suggests that the C-terminal region may play a dual role, serving both as a channel gate and as a shuttle mediating the delivery of copper ions from the extracellular hCtr1 selectivity filter to intracellular metallochaperones. Our findings thus contribute to a more complete understanding of the mechanism of hCtr1-mediated Cu(I) uptake and provide a conceptual basis for developing mechanism-based therapeutics for treating pathological conditions linked to de-regulated copper metabolism.
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Wilson disease (WD) is an inherited disorder of copper metabolism that leads to copper accumulation and toxicity in the liver and brain. It is caused by mutations in the adenosine triphosphatase ...copper transporting β gene (ATP7B), which encodes a protein that transports copper from hepatocytes into the bile. We studied ATP7B-deficient cells and animals to identify strategies to decrease copper toxicity in patients with WD.
We used RNA-seq to compare gene expression patterns between wild-type and ATP7B-knockout HepG2 cells exposed to copper. We collected blood and liver tissues from Atp7b−/− and Atp7b+/− (control) rats (LPP) and mice; some mice were given 5 daily injections of an autophagy inhibitor (spautin-1) or vehicle. We obtained liver biopsies from 2 patients with WD in Italy and liver tissues from patients without WD (control). Liver tissues were analyzed by immunohistochemistry, immunofluorescence, cell viability, apoptosis assays, and electron and confocal microscopy. Proteins were knocked down in cell lines using small interfering RNAs. Levels of copper were measured in cell lysates, blood samples, liver homogenates, and subcellular fractions by spectroscopy.
After exposure to copper, ATP7B-knockout cells had significant increases in the expression of 103 genes that regulate autophagy (including MAP1LC3A, known as LC3) compared with wild-type cells. Electron and confocal microscopy visualized more autophagic structures in the cytoplasm of ATP7B-knockout cells than wild-type cells after copper exposure. Hepatocytes in liver tissues from patients with WD and from Atp7b−/− mice and rats (but not controls) had multiple autophagosomes. In ATP7B-knockout cells, mammalian target of rapamycin (mTOR) had decreased activity and was dissociated from lysosomes; this resulted in translocation of the mTOR substrate transcription factor EB to the nucleus and activation of autophagy-related genes. In wild-type HepG2 cells (but not ATP7B-knockout cells), exposure to copper and amino acids induced recruitment of mTOR to lysosomes. Pharmacologic inhibitors of autophagy or knockdown of autophagy proteins ATG7 and ATG13 induced and accelerated the death of ATP7B-knockout HepG2 cells compared with wild-type cells. Autophagy protected ATP7B-knockout cells from copper-induced death.
ATP7B-deficient hepatocytes, such as in those in patients with WD, activate autophagy in response to copper overload to prevent copper-induced apoptosis. Agents designed to activate this autophagic pathway might decrease copper toxicity in patients with WD.
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Copper (Cu) is an essential micronutrient involved in a variety of fundamental biological processes. Recently, disorder of Cu homeostasis can be observed in many malignancies. Elevated Cu levels in ...serum and tissue are correlated with cancer progression. Hence, targeting Cu has emerged as a novel strategy in cancer treatment. This review provides an overview of physiological Cu metabolism and its homeostasis, followed by a discussion of the dysregulation of Cu homeostasis in cancer and the effects of Cu on cancer progression. Finally, recent therapeutic advances using Cu coordination complexes as anticancer agents, as well as the mechanisms of their anti‐cancer action are discussed. This review contributes full comprehension to the role of Cu in cancer and demonstrates the broad application prospect of Cu coordination compounds as potential therapeutic agents.
A feeding trial was conducted to evaluate the dietary copper requirement of red drum (Sciaenops ocellatus) and compare the bioavailability of copper sulphate (CuSO4) and copper‐ethanolamine. A basal ...diet was formulated using semi‐purified ingredients and analysed to contain 3 mg Cu/kg. Both copper sources were supplemented to the basal diet at either 5, 10 or 20 mg Cu/kg of dry diet. No significant differences were observed in growth performance of fish fed the various diets. However, red drum fed all copper‐supplemented diets retained more copper in liver and whole‐body tissues compared to fish fed the basal diet. Within both inorganic and organic copper treatments, the highest tissue copper concentrations were observed in fish fed diets supplemented with 10 mg Cu/kg. No significant differences were detected in net copper retention regardless of the nature of the copper source; hence, the bioavailability of copper sulphate and copper‐ethanolamine complex was not different in the diets for juvenile red drum. Furthermore, the minimum copper requirement for growth performance of juvenile red drum appeared to be satisfied when fish were fed the basal diet containing 3 mg Cu/kg diet, and no detrimental effects were observed in red drum fed diets supplemented with 20 mg Cu/kg.
Dense Cu sub(2)ZnSnSe sub(4) (CZTSe) thin films with large grains of 1-6 mu m were prepared by sputtering a metallic Cu-Zn-Sn target followed by a selenization process at 600 degree C. Selenization ...of Cu-Zn-Sn metallic films with the aid of (SnSe sub(2)+Se) and CuSe sub(2) was explained, which involved the nucleation and growth stages. The design of modified Cu(In,Ga)Se sub(2) barrier layer prevented high-temperature reactions between the Mo electrode and as-deposited film and led to a pore-free interface. Using our simple approach, passivated and large grains were formed in an absorption layer, which is important for fabricating CZTSe solar cells.
•The growth was decreased with increasing of both forms of Cu doses.•Copper was increased in all tissues with increasing of both forms of Cu doses.•The remaining tissues and the liver contributed ...most of the total Cu in the body.•Either Cu-NPs or CuSO4 caused tissues oxidative stress and cell apoptosis.•Dissolved Cu was more toxic than Cu-NPs.
Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. In this study the effects of Cu-NPs and soluble Cu were investigated on juvenile Epinephelus coioides. The fish were exposed in triplicate to control, 20 or 100μgCuL−1 as either copper sulphate (CuSO4) or Cu-NPs in a semi-static aqueous culture for 25 days. The growth parameters were significantly lower at 100μgCuL−1 as CuSO4 or Cu-NPs treatment compared to control. Time-dependent Cu accumulation in all tissues increased with increasing the Cu dose. The percentage of total Cu found in remaining tissues (head, bones, fins, etc.) decreased more in the CuSO4 than Cu-NPs treatment after 25 days, but increased in all other tissues (especially in liver). Compared with the control, either Cu-NPs or CuSO4 induced higher malonaldehyde concentration in tissues by overwhelming total superoxide dismutase activity, total glutathione concentration and Na+/K+-ATPase activity, but the opposite results were recorded for the brain. With increasing the CuSO4 or Cu-NPs dose, apoptosis was exacerbated in the liver and gills, more so by CuSO4 than Cu-NPs. Overall, these findings showed that Cu-NPs had the toxic effects similar to dissolved Cu; hence, Cu-NPs need to be included in the assessment of toxicological impacts in the aquatic environment.
Correction for 'Development of a multi-isotopic (Pb, Fe, Cu) analytical protocol in gold matrices for ancient coin provenance studies' by Louise de Palaminy
et al.
,
J. Anal. At. Spectrom.
, 2024,
...https://doi.org/10.1039/d3ja00312d
.
Copper–zinc superoxide dismutase (Sod1) is a critical antioxidant enzyme that rids the cell of reactive oxygen through the redox cycling of a catalytic copper ion provided by its copper chaperone ...(Ccs). Ccs must first acquire this copper ion, directly or indirectly, from the influx copper transporter, Ctr1. The three proteins of this transport pathway ensure careful trafficking of copper ions from cell entry to target delivery, but the intricacies remain undefined. Biochemical examination of each step in the pathway determined that the activation of the target (Sod1) regulates the Ccs·Ctr1 interaction. Ccs stably interacts with the cytosolic C-terminal tail of Ctr1 (Ctr1c) in a copper-dependent manner. This interaction becomes tripartite upon the addition of an engineered immature form of Sod1 creating a stable Cu(I)-Ctr1c·Ccs·Sod1 heterotrimer in solution. This heterotrimer can also be made by the addition of a preformed Sod1·Ccs heterodimer to Cu(I)-Ctr1c, suggestive of multiple routes to the same destination. Only complete Sod1 activation (i.e. active site copper delivery and intra-subunit disulfide bond formation) breaks the Sod1·Ccs·Ctr1c complex. The results provide a new and extended view of the Sod1 activation pathway(s) originating at cellular copper import.
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