Excess Copper Research Articles

A co-opted endogenous retroviral envelope promotes cell survival by controlling CTR1-mediated copper transport and homeostasis

Copper is a critical element for eukaryotic life involved in numerous cellular functions, including redox balance, but is toxic in excess. Therefore, tight regulation of copper acquisition and homeostasis is essential for cell physiology and survival. Here, we identify a different regulatory mechanism for cellular copper homeostasis that requires the presence of an endogenous retroviral envelope glycoprotein called Refrex1. We show that cells respond to elevated extracellular copper by increasing the expression of Refrex1, which regulates copper acquisition through interaction with the main copper transporter CTR1. Downmodulation of Refrex1 results in intracellular copper accumulation leading to reactive oxygen species (ROS) production and subsequent apoptosis, which is prevented by copper chelator treatment. Our results show that Refrex1 has been co-opted for its ability to regulate copper entry through CTR1 in order to limit copper excess, redox imbalance, and ensuing cell death, strongly suggesting that other endogenous retroviruses may have similar metabolic functions among vertebrates.

Quercetin Alleviates Toxicity Induced by High Levels of Copper in Porcine Follicular Granulosa Cells by Scavenging Reactive Oxygen Species and Improving Mitochondrial Function.

CuSO4 is the most commonly used feed additive in pig production at present, but long-term ingestion of excessive copper would lead to chronic copper toxicity. High copper could reduce the reproductive efficiency of sows and seriously affect the development of the pig industry. Quercetin (QUE), a powerful antioxidant, reduces toxicity of a number of heavy metals. Porcine granulosa cells (pGCs) are crucial to the fate of follicle development. The present study found that high concentrations of CuSO4 induced ROS production, which resulted in decreased mRNA expression of antioxidant-related genes GPX4, CAT, and SOD2 and increased mRNA expression of SOD1, TRX, and HO-1. The protein expression of antioxidant enzymes SOD2 and HO-1 decreased. Moreover, the concentration of MDA increased, the activity of CAT decreased, and the content of GSH decreased. After high copper treatment, the mitochondrial membrane potential (MMP) was decreased and the morphological structure was changed. However, the combined treatment with Quercetin (QUE) reversed these changes, and the level of cellular oxidative stress decreased. Therefore, we conclude that high copper has oxidative toxicity to pGCs, and QUE could remove the ROS induced by high copper, protect mitochondria from oxidative stress damage, and improve the function of pGCs.

Remediation of the microecological environment of heavy metal-contaminated soil with fulvic acid, improves the quality and yield of apple

The excessive application of chemical fertilizers and pesticides in apple orchards is responsible for high levels of manganese and copper in soil, and this poses a serious threat to soil health. We conducted a three-year field experiment to study the remediation effect and mechanism of fulvic acid on soil with excess manganese and copper. The exogenous application of fulvic acid significantly reduced the content of manganese and copper in soil and plants; increased the content of calcium; promoted the growth of apple plants; improved the fruit quality and yield of apple; increased the content of chlorophyll; increased the activity of superoxide dismutase, peroxidase, and catalase; and reduced the content of malondialdehyde. The number of soil culturable microorganisms, soil enzyme activity, soil microbial community diversity, and relative abundance of functional bacteria were increased, and the detoxification of the glutathione metabolism function was enhanced. The results of this study provide new insights that will aid the remediation of soil with excess manganese and copper using fulvic acid.

Novel mutations in ATP7B in Chinese patients with Wilson's disease and identification of kidney disorder of thinning of the glomerular basement membrane.

Wilson's disease is an autosomal recessive disorder caused by ATP7B pathogenic mutations. The hallmark of this disorder mainly consists of liver involvement, neurologic dysfunction and psychiatric features. In addition, the kidneys can also be affected by excessive copper deposition. A total of 34 patients clinically diagnosed with WD were recruited. They underwent ATP7B gene sequencing and clinical data of symptoms, examination, and treatment were collected. Moreover, renal pathology information was also investigated. We identified 25 potentially pathogenic ATP7B variants (16 missense, 5 frameshift, 3 splicing variants and 1 large deletion mutation) in these 34 WD patients, 5 of which were novel. In our cases, the most frequent variant was c.2333G>T (R778L, 39.06%, exon 8), followed by c.2621C>T (A874V, 10.94%, exon 11) and c.3316G>A (V1106I, 7.81%, exon 11). Furthermore, we described the thinning of the glomerular basement membrane as a rare pathologically damaging feature of Wilson's disease for the first time. Additionally, two patients who received liver transplant were observed with good prognosis in present study. Our work expanded the spectrum of ATP7B variants and presented rare renal pathological feature in WD patients, which may facilitate the development of early diagnosis, counseling, treatment regimens of WD.

Construction of Lung Adenocarcinoma Prognosis Model and Drug Sensitivity Analysis Based on Cuproptosis Related Genes

Lung cancer is one of the most common malignant tumors in the world, and the current lung cancer screening and treatment strategies are constantly improving, but its 5-year survival rate is still very low, which seriously endangers human health. Therefore, it is critical to explore new biomarkers to provide personalized treatment and improve the prognosis. Cuproptosis is a newly discovered type of cell death, which is due to the accumulation of excess copper ions in the cell, eventually leading to cell death, which has been suggested by studies to be closely related to the occurrence and development of lung adenocarcinoma (LUAD). Based on The Cancer Genome Atlas (TCGA) database, this study explored the association between cuproptosis-related genes (CRGs) and LUAD prognosis, established a prognostic risk model, and analyzed the interaction between CRGs and LUAD immune cell infiltration. The RNA-seq data of LUAD tissue and paracancerous or normal lung tissue were downloaded from the TCGA database; the RNA-seq data of normal lung tissue was downloaded from the Genotype-tissue Expression (GTEx) database, and the data of 462 lung adenocarcinoma cases were downloaded from the Gene Expression Omnibus repository (GEO) as verification. T the risk score model to assess prognosis was constructed by univariate Cox and Lasso-Cox regression analysis, and the predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Immune-related and drug susceptibility analysis was further performed on high- and low-risk groups. A total of 1656 CRGs and 1356 differentially expressed CRGs were obtained, and 13 CRGs were screened out based on univariate Cox and Lasso-Cox regression analysis to construct a prognostic risk model, and the area under the curves (AUCs) of ROC curves 1-, 3- and 5- year were 0.749, 0.740 and 0.689, respectively. Further study of immune-related functions and immune checkpoint differential analysis between high- and low-risk groups was done. High-risk groups were more sensitive to drugs such as Savolitinib, Palbociclib, and Cytarabine and were more likely to benefit from immunotherapy. The risk model constructed based on 13 CRGs has good prognostic value, which can assist LUAD patients in individualized treatment, and provides an important theoretical basis for the treatment and prognosis of LUAD.

Analysis of the failure mechanism of a blast furnace tuyere sleeve with protective coating

The tuyere sleeve plays a crucial role in blast furnaces, enduring a harsh working environment that frequently leads to substantial damage. One approach to extend the service life of tuyere sleeve is to prepare a Ni-based alloy protective layer on its surface. However, there is a lack of experimental information concerning the failure of these protective coatings after real-world use. Therefore, in this study, the failure of a blast furnace tuyere sleeve with protective layer was investigated. Characterizations were performed on both the “original” and failed protective layers, as well as the scale layer. The “original” protective layer exhibits two main issues: excessive copper dilution (＞40%) and significant Ni-Cr enrichment at the interface, which may be attributed to inadequate preparation techniques. The failed protective layer surface is covered with molten slag and iron, and there is a crack running almost completely through the coating. Both oxidation reaction and sulfur corrosion are important factors contributing to the accelerated failure of the coating. Moreover, it is suggested that the compositional inhomogeneity of the protective layer of the tuyere sleeve leads to local stress concentration within the coating, which is an internal cause for thermal fatigue crack formation. Additionally, it can be inferred that the molten slag and iron falling onto the protective layer surface under abnormal furnace conditions not only accelerates crack initiation and propagation but also directly melts the coating material or causes interface reactions, leading to the failure of the protective layer.

The emerging role of copper in depression.

Copper (Cu) is an essential trace element in the brain and serves as an important cofactor for numerous enzymes involved in a wide range of biochemical processes including neurobehavioral, mitochondrial respiration, and antioxidant effects. Recent studies have demonstrated that copper dyshomeostasis is tightly associated with the development of depression by inducing oxidative stress and inflammatory responses. However, these findings have remained controversial so far. Cumulative studies have shown a positive association, while some other studies showed no association and even a negative association between serum/plasma copper level and depression. Based on these conflicted results, the association was speculated to be due to the clinical features of the population, stages of the disease, severity of copper excess, and types of specimens detected in these studies. In addition, there was an inverse association between dietary copper intake and depression. Furthermore, increasing copper intake could influence dietary zinc and iron intake to prevent and treat depression. Thus, copper supplementation may be a good measure to manage depression. This review provided a deeper understanding of the potential applicability of copper in the prevention and treatment of depression.

Intelligent gold nanoparticles for malignant tumor treatment via spontaneous copper manipulation and on-demand photothermal therapy based on copper induced click chemistry.

The excessive copper in tumor cells is crucial for the growth and metastasis of malignant tumor. Herein, we fabricated a nanohybrid to capture, convert and utilize the overexpressed copper in tumor cells, which was expected to achieve copper dependent photothermal damage of primary tumor and copper-deficiency induced metastasis inhibition, generating accurate and effective tumor treatment. The nanohybrid consistsed of 3-azidopropylamine, 4-ethynylaniline and N-aminoethyl-N'-benzoylthiourea (BTU) co-modified gold nanoparticles (AuNPs). During therapy, the BTU segment would specifically chelate with copper in tumor cells after endocytosis to reduce the intracellular copper content, causing copper-deficiency to inhibit the vascularization and tumor migration. Meanwhile, the copper was also rapidly converted to be cuprous by BTU, which further catalyzed the click reaction between azido and alkynyl on the surface of AuNPs, resulting in on-demand aggregation of these AuNPs. This process not only in situ generated the photothermal agent in tumor cells to achieve accurate therapy avoiding unexpected damage, but also enhanced its retention time for sustained photothermal therapy. Both in vitro and in vivo results exhibited the strong tumor inhibition and high survival rate of tumor-bearing mice after application of our nanohybrid, indicating that this synergistic therapy could offer a promising approach for malignant tumor treatment. STATEMENT OF SIGNIFICANCE: The distinctive excessive copper in tumor cells is crucial for the growth and metastasis of tumor. Therefore, we fabricated intelligent gold nanoparticles to simultaneously response and reverse this tumorigenic physiological microenvironment for the synergistic therapy of malignant tumor. In this study, for the first time we converted and utilized the overexpressed Cu2+ in tumor cells to trigger intracellular click chemistry for tumor-specific photothermal therapy, resulting in accurate damage of primary tumor. Moreover, we effectively manipulated the content of Cu2+ in tumor cells to suppress the migration and vascularization of malignant tumor, resulting in effective metastasis inhibition.

Copper exerts cytotoxicity through inhibition of iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins.

Copper is an essential mineral nutrient that provides the cofactors for some key enzymes. However, excess copper is paradoxically cytotoxic. Wilson's disease is an autosomal recessive hereditary disease characterized by pathological copper accumulation in many organs, with high mortality and disability. Nevertheless, many questions about the molecular mechanism in Wilson's disease remain unknown and there is an imperative need to address these questions to better exploit therapeutic strategy. In this study, we constructed the mouse model of Wilson's disease, ATP7A-/- immortalized lymphocyte cell line and ATP7B knockdown cells to explore whether copper could impair iron-sulfur cluster biogenesis in eukaryotic mitochondria. Through a series of cellular, molecular, and pharmacological analyses, we demonstrated that copper could suppress the assembly of Fe-S cluster, decrease the activity of the Fe-S enzyme and disorder the mitochondrial function both in vivo and in vitro. Mechanistically, we found that human ISCA1, ISCA2 and ISCU proteins have a strong copper-binding activity, which would hinder the process of iron-sulfur assembly. Of note, we proposed a novel mechanism of action to explain the toxicity of copper by providing evidence that iron-sulfur cluster biogenesis may be a primary target of copper toxicity both in cells and mouse models. In summary, the current work provides an in-depth study on the mechanism of copper intoxication and describes a framework for the further understanding of impaired Fe-S assembly in the pathological processes of Wilson's diseases, which helps to develop latent therapeutic strategies for the management of copper toxicity.

Integration of Tumor Elimination And Tissue Regeneration via Selective Manipulation of Physiological Microenvironments Based on Intelligent Nanocomposite Hydrogel for Postoperative Treatment of Malignant Melanoma

AbstractTumor residue and tissue damage normally occurred after surgical treatment of malignant melanoma, and the effective postoperative therapy is still a challenge because the treatment requests simultaneous but opposite manipulation of tumor cells and healthy cells. Herein, MBGP‐Gel, a thermosensitive and biodegradable hydrogel incorporating S‐nitrosoglutathione (GSNO) loaded and N‐aminoethyl‐N’‐benzoyl thiourea (BTU) modified MSNs (MBGP NPs), was designed to utilize the significant difference of copper content between tumor cells and healthy cells to regulate various physiological microenvironments for integrative therapy of tumor elimination, metastasis inhibition and tissue regeneration. The MBGP‐Gel underwent sol‐gel transformation at body temperature after injection, and continuously released MBGP nanoparticles. In tumor cells, these nanoparticles would chelate the excess copper to inhibit the tumor migration. Meanwhile, copper was reduced to cuprous, which further catalyzed the abundant H2O2 and GSNO to produce oxygen species (ROS) and nitric oxide (NO), respectively. The ROS and the reaction product of ROS and NO (ONOO) would significantly damage the tumor tissue. In contrast, MBGP nanoparticles entered healthy cells only generate appropriate amount of NO to accelerate tissue healing. Both in vitro and in vivo results showed that the nanocomposite hydrogel could inhibit the growth and metastasis of malignant melanoma and promote the skin regeneration, which offered an promising strategy for postoperative treatment of various tumors.

Targeting copper metabolism: a promising strategy for cancer treatment.

Copper is an essential micronutrient that plays a critical role in many physiological processes. However, excessive copper accumulation in cancer cells has been linked to tumor growth and metastasis. This review article explores the potential of targeting copper metabolism as a promising strategy for cancer treatment. Excessive copper accumulation in cancer cells has been associated with tumor growth and metastasis. By disrupting copper homeostasis in cancer cells and inducing cell death through copper-dependent mechanisms (cuproplasia and cuprotosis, respectively), therapies can be developed with improved efficacy and reduced side effects. The article discusses the role of copper in biological processes, such as angiogenesis, immune response, and redox homeostasis. Various approaches for targeting copper metabolism in cancer treatment are examined, including the use of copper-dependent enzymes, copper-based compounds, and cuprotosis-related genes or proteins. The review also explores strategies like copper chelation therapy and nanotechnology for targeted delivery of copper-targeting agents. By understanding the intricate network of cuprotosis and its interactions with the tumor microenvironment and immune system, new targets for therapy can be identified, leading to improved cancer treatment outcomes. Overall, this comprehensive review highlights the significant potential of targeting copper metabolism as a promising and effective approach in cancer treatment, while providing valuable insights into the current state of research in this field.

A novel cuproptosis-related diagnostic gene signature and differential expression validation in atherosclerosis

Atherosclerosis (AS) is a major contributor to morbidity and mortality worldwide. However, the molecular mechanisms and mediator molecules involved remain largely unknown. Copper, which plays an essential role in cardiovascular disease, has been suggested as a potential risk factor. Copper homeostasis is closely related to the occurrence and development of AS. Recently, a new cell death pathway called cuproptosis has been discovered, which is driven by intracellular copper excess. However, no previous studies have reported a relationship between cuproptosis and AS. In this study, we integrated bulk and single-cell sequencing data to screen and identify key cuproptosis-related genes in AS. We used correlation analysis, enrichment analysis, random forest, and other bioinformatics methods to reveal their relationships. Our findings report, for the first time, the involvement of cuproptosis-related genes FDX1, SLC31A1, and GLS in atherogenesis. FDX1 and SLC31A1 were upregulated, while GLS was downregulated in atherosclerotic plaque. Receiver operating characteristic curves demonstrate their potential diagnostic value for AS. Additionally, we confirm that GLS is mainly expressed in vascular smooth muscle cells, and SLC31A1 is mainly localized in macrophages of atherosclerotic lesions in experiments. These findings shed light on the cuproptosis landscape and potential diagnostic biomarkers for AS, providing further evidence about the vital role of cuproptosis in atherosclerosis progression.

Exogenous acetone O-(2-naphthylsulfonyl)oxime improves the adverse effects of excess copper by copper detoxification systems in maize

The current study is to elucidate the responses of maize seedlings to excess copper and acetone O-(2-naphthylsulfonyl)oxime (NS) pretreatment. The study was divided into the following experimental groups: 18 h distilled water (DW) control (C), 6 h 0.3 mM NS + then 12 h DW (NS), 6 h DW + then 12 h 1 mM CuSO4.5H2O (CuS), 0.3 mM NS for 6 h + then 1 mM CuSO4.5H2O (NS + CuS) for 12 h. When the NS + CuS group is compared with the CuS group; It accumulated 10% more copper, while the ABA, H2O2, MDA, and carotenoid contents decreased significantly, the total chlorophyll, proline, gallic acid, ascorbic acid, catechol, trans-P-qumaric acid, and cinnamic acid contents increased. While SOD activity, which is one of the antioxidant system enzymes, decreased with NS application, GPX, CAT, and APX activities increased despite copper stress. When all the findings are evaluated as a whole, exogenous NS, despite excessive copper, ameliorated the adverse effects of copper stress by increasing the effectiveness of the enzymatic and non-enzymatic components of the antioxidant system and the contents of phenolic substances. In addition, increasing the copper content by 10% reveals its importance in terms of NS phytoremediation. Abbreviation: Style-sheet: When full form and abbreviated form both are used as keywords, retain both as provided by the author

Toxicity, physiological, and morphological alterations of Indian camphorweed (Pluchea indica) in response to excess copper.

Indian camphorweed (Pluchea indica (L.) Less.) is used as herbal tea due to the presence of volatile aromatic oils and several phytochemical compounds. The aim of this study was to assess the impact of copper (Cu) contamination on the physiology and morphology of P. indica, and the health risks associated with its consumption as tea. The cuttings of P. indica were subjected to 0mM (control), 5mM (low Cu), and 20mM (excess Cu) of CuSO4 treatments for 1, 2, and 4weeks. Thereafter, Cu contamination as well as physiological and morphological parameters were assessed. Cu accumulation was higher in the root tissues of plants (25.8 folds higher as compared to the leaves) grown under 20mM CuSO4 for 4weeks. This increased Cu accumulation resulted in the inhibition of root length, root fresh weight, and root dry weight. Cu concentration was found maximum (1.36μgg-1 DW) in the leaf tissues under 20mM Cu exposure for 4weeks, with the highest target hazard quotient (THQ = 1.85), whereas Cu was not detected in control. Under exposure to 20mM Cu treatment for 4weeks, leaf greenness, maximum quantum yield of photosystem II, and photon yield of photosystem II diminished by 21.4%, 16.1%, and 22.4%, respectively, as compared to the control. Leaf temperature was increased by 2.5°C, and the crop stress index (CSI) exceeded 0.6 when exposed to 20mM Cu treatment for 2 and 4weeks; however, the control had a CSI below 0.5. This led to a reduced transpiration rate and stomatal conductance. In addition, the net photosynthetic rate was also found sensitive to Cu treatment, which resulted in decreased shoot and root growth. Based on the key results, it can be suggested that P. indica herbal tea derived from the foliage of plants grown under a 5mM Cu level (0.75μgg-1 DW) with a target hazard quotient below one aligns with the recommended dietary intake of Cu in leafy vegetables. The study recommends choosing cuttings from plants with a small canopy as plant material in the greenhouse microclimates to validate the growth performance in the Cu-contaminated soil and simulate the natural shrub architecture and life cycle.

Trifloxystrobin Pretreatment Alleviates Excessive Copper Stress in Wheat (Triticum aestivum L.)

Protective role of Trifloxystrobin pretreatment against excessive copper-related abiotic stress in Triticum aestivum L. was determined in two Turkish wheat cultivars, Sönmez and Gerek 79. Ten-day-old seedlings were pretreated with 20 µM and 80 µM Trifloxystrobin. A group of seedlings was harvested without exposure to Trifloxystrobin as a control. Two days after, seedlings were treated with copper(II) chloride. Seedlings were harvested on the 20th day after sowing. The growth level of the groups was evaluated by measuring the length, fresh weight and shoot dry weight of shoots. Chlorophyll a + b, carotenoid and anthocyanin contents as well as proline levels were assessed. Lipid peroxidation and total activities of superoxide dismutase, peroxidase and glutathione reductase were analyzed to predict the oxidative stress levels. Both cultivars exhibited similar responses to the treatments. Trifloxystrobin doses did not cause damage on plants when applied alone. Seedlings subjected to excessive doses of copper showed significant reductions in growth parameters, as well as chlorophyll and carotenoid pigments. Conversely, copper caused a remarkable increase in anthocyanin, proline and malondialdehyde accumulation. Superoxide dismutase and peroxidase activities increased, while glutathione reductase activity decreased in copper-stressed plants. Trifloxystrobin pretreatment strengthens the antioxidant defense system. All parameters were positively affected by Trifloxystrobin pretreatment. As the dose of Trifloxystrobin increased, the severity of stress decreased in both genotypes. Trifloxystrobin pretreatment is a promising method for reducing copper-induced damage in T. aestivum.

Hepatic depletion of nucleolar protein mDEF causes excessive mitochondrial copper accumulation associated with p53 and NRF1 activation

Copper is an essential component in the mitochondrial respiratory chain complex IV (cytochrome c oxidases). However, whether any nucleolar factor(s) is(are) involved in regulating the mitochondrial copper homeostasis remains unclear. The nucleolar localized Def-Capn3 protein degradation pathway cleaves target proteins, including p53, in both zebrafish and human nucleoli. Here, we report that hepatic depletion of mDEF in mice causes an excessive copper accumulation in the mitochondria. We find that mDEF-depleted hepatocytes show an exclusion of CAPN3 from the nucleoli and accumulate p53 and NRF1 proteins in the nucleoli. Furthermore, we find that NRF1 is a CAPN3 substrate. Elevated p53 and NRF1 enhances the expression of Sco2 and Cox genes, respectively, to allow more copper acquirement in the mDefloxp/loxp, Alb:Cre mitochondria. Our findings reveal that the mDEF-CAPN3 pathway serves as a novel mechanism for regulating the mitochondrial copper homeostasis through targeting its substrates p53 and NRF1.

Bioinformatics prediction and experimental verification identify cuproptosis-related lncRNA as prognosis biomarkers of hepatocellular carcinoma

Cuproptosis is a form of cell death caused by intracellular copper excess, which plays an important regulatory role in the development and progression of cancers, including hepatocellular carcinoma (HCC), a prevalent malignancy with high morbidity and mortality.This study aimed to create a cuproptosis associated long non-coding RNAs (CAlncRNAs)signature to predict HCC patient survival and immunotherapy response. Firstly, we identified 509 CAlncRNAs using Pearson correlation analysis in The Cancer Genome Atlas (TCGA) datasets, before the three CAlncRNAs (MKLN1-AS, FOXD2-AS1, LINC02870) with the most prognostic value were further screened. Then, we constructed a prognostic risk model for HCCwas using univariate and LASSO Cox regression analyses. Multivariate Cox regression analyses illustrated that this model was an independent prognostic factor for overall survival (OS) prediction, outperforming traditional clinicopathological factors. And the risk score not only could be prognostic factors independent of other factors but also suited for patients with diverse ages, stages, and grades. The 1-, 3-, and 5- years areas under the curves (AUC) values of the model were 0.759, 0.668 and 0.674 respectively. Pathway analyses showed that the high-risk groupenriched in immune-related pathways. Importantly, patients with higher risk scores exhibited higher mutation frequency, higher TMB scores, and lower TIDE scores. Besides, we screened for two chemical drugs (A-443654 and Pyrimethamine) with the greatest value for high-risk HCC patients. Finally, the abnormal high expression of the three CAlncRNAs were confirmed in HCC tissues and cells by Real Time Quantitative PCR (RT-qPCR). And proliferative, migratory and invasion abilities of HCC cell were restrained via silencing CAlncRNAs expression in vitro.In summary, we built a CAlncRNAs-based risk score model, which can be a candidate for HCC patients prognostic prediction and offer some useful information for immunotherapies.

Preparation of CdTe quantum dots for detecting Cu(II) ions

Although copper is needed by the human body, excessive copper can cause diarrhea, vomiting, and neurological disorders. In this study, CdTe semiconductor quantum dots (QDs) with different emission wavelengths were fabricated and used for detection of copper ions. By controlling the temperature, nucleation and growth of the crystals in the aqueous phase were separated, which improved the optical properties of QDs. They were characterized with Fourier-transform infrared (FT-IR), Transmission electron microscope (TEM) and X-ray diffraction (XRD). After being coated by the sol-gel method, the QDs were used to detect Cu(II) ions. There was a good linear relationship between the concentration of Cu(II) ions and the quenching efficiency of fluorescent probes over the range 0–1 mg L−1, and the detection limit was 1.18 μg L−1 (n = 10). Ratiometric fluorescent probes were also fabricated, which exhibited better Cu(II) ion detection, with a detection limit as 0.13 μg L−1 (0.002 μmol/L) that was far lower than the detection standard of copper ions in water.

Expression and copper binding studies of a Plasmodium falciparum protein with Cox19 copper binding motifs

Copper can exist in an oxidized and a reduced form, which enables the metal to play essential roles as a catalytic co-factor in redox reactions in many organisms. Copper confers redox activity to the terminal electron transport chain cytochrome c oxidase protein. Cytochrome c oxidase in yeast obtains copper for the CuB site in the Cox1 subunit from Cox11 in association with Cox19. When copper is chelated in growth medium, Plasmodium falciparum parasite development in infected red blood cells is inhibited and excess copper is toxic for the parasite. The gene of a 26 kDa Plasmodium falciparum PfCox19 protein with two Cx9C Cox19 copper binding motifs, was cloned and expressed as a 66 kDa fusion protein with maltose binding protein and affinity purified (rMBP-PfCox19). rMBP-PfCox19 bound copper measured by: a bicinchoninic acid release assay; an in vivo bacterial host growth inhibition assay; ascorbate oxidation inhibition and differential scanning fluorimetry. The native protein was detected by antibodies raised against rMBP-PfCox19. PfCox19 binds copper and is predicted to associate with PfCox11 in the insertion of copper into the CuB site of Plasmodium cytochrome c oxidase. Characterisation of the proteins involved in Plasmodium spp. copper metabolism will help us understand the role of cytochrome c oxidase and this essential metal in Plasmodium homeostasis.

Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P

Selenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson’s disease. Accordingly, SELENOP levels were low in serum of Wilson’s disease patients and Wilson’s rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain.