Semen copper in normal and infertile subjects.

Concentration of copper in seminal plasma was found to be less than that of normal in cases of oligospermia and azoospermia. It was more in oligoasthenospermia and asthenospermia when compared with that of normal. Chances of initiation of sperm motility by copper is discussed alongwith the inhibitory role it plays.     

Alopecia induced in young mice by exposure to excess dietary zinc

Second generation mice were exposed to normal (50 ppm, Group I) or excess (2000 ppm, Group II) zinc in the maternal diet during gestation and lactation, then weaned and continued on the mother's diet until sacrifice at 8 weeks. Tibia zinc reflected dietary intake. Group II had reduced plasma copper, body weight, and hematocrit; the second coat of hair appeared late and was lighter in color than Group I, possibly as an effect of copper and pigmentation development and hair growth.     

Alopecia induced in young mice by exposure to excess dietary zinc

Summary Second generation mice were exposed to normal (50 ppm, Group I) or excess (2000 ppm, Group II) zinc in the maternal diet during gestation and lactation, then weaned and continued on the mother's diet until sacrifice at 8 weeks. Tibia zinc reflected dietary intake. Group II had reduced plasma copper, body weight, and hematocrit; the second coat of hair appeared late and was lighter in color than Group I, possibly as an effect of copper and pigmentation development and hair growth.     

Effects of CO2 exposure on distribution of various forms of iron and copper in guinea-pig tissues

The effects on iron and copper distribution and metabolism of exposure to high levels of CO2 were studied in the guinea-pig. Mature, male animals were placed in an atmosphere of 15% CO2, 21% O2 (balance N2), and sacrificed from 1 h to 1 week thereafter. Total iron and copper concentrations of blood, liver, spleen and bone, as well as concentrations of heme and ferritin iron, were measured together with blood hematocrit, reticulocytes, plasma hemoglobin, plasma ceruloplasmin and copper concentrations. The results show clearly that rapid and sustained red cell damage or hemolysis ensued several h from the start of CO2 treatment. This resulted in loss of iron and copper from the blood, an influx of both elements into liver, spleen and bone, and a rise in plasma ceruloplasmin. Influx of iron into liver and spleen caused an accumulation of ferritin, the main site for iron storage in cells. Following the effect on red cells, there was an accumulation of heme iron, and a decreased hematocrit, best explained by a depressed activity of the reticuloendothelial and erythropoietic systems. A period of adaptation succeeded these events, in which all blood parameters and most tissue values returned to normal, despite the continuing presence of high CO2. The only changes not reversed were the elevations in liver, spleen and bone iron stores. These remained high, with a net accumulation of greater than 2 mg iron, or 3-4 times more than originally present. The results indicate that at least in the guinea-pig, high CO2 exposure results in red cell damage and other events leading to an accumulation of additional iron in the body; also, that iron accumulated as ferritin and hemosiderin in liver and spleen may not be readily available to restore blood hemoglobin concentrations on an acute basis.     

The pre-history of hemocyanin. The discovery of copper in the blood of molluscs

The presence of copper in molluscs was discovered in 1833 by Bartolomeo Bizio, a Venetian chemist, who found copper in marine gastropods of the family Muricidae during his studies on the purple dye he had isolated from these animals. Bizio was so surprised by this finding that he extended his analysis to several other invertebrate species in which he identified the metal.     

Effects of CO2 exposure on distribution of various forms of iron and copper in guinea-pig tissues

Summary The effects on iron and copper distribution and metabolism of exposure to high levels of CO₂ were studied in the guinea-pig. Mature, male animals were placed in an atmosphere of 15% CO₂, 21% O₂ (balance N₂), and sacrificed from 1 h to 1 week thereafter. Total iron and copper concentrations of blood, liver, spleen and bone, as well as concentrations of heme and ferritin iron, were measured together with blood hematocrit, reticulocytes, plasma hemoglobin, plasma ceruloplasmin and copper concentrations. The results show clearly that rapid and sustained red cell damage or hemolysis ensued several h from the start of CO₂ treatment. This resulted in loss of iron and copper from the blood, an influx of both elements into liver, spleen and bone, and a rise in plasma ceruloplasmin. Influx of iron into liver and spleen caused an accumulation of ferritin, the main site for iron storage in cells. Following the effect on red cells, there was an accumulation of heme iron, and a decreased hematocrit, best explained by a depressed activity of the reticuloendothelial and erythropoietic systems. A period of adaptation succeeded these events, in which all blood parameters and most tissue values returned to normal, despite the continuing presence of high CO₂. The only changes not reversed were the elevations in liver, spleen and bone iron stores. These remained high, with a net accumulation of >2 mg iron, or 3–4 times more than originally present. The results indicate that at least in the guinea-pig, high CO₂ exposure results in red cell damage and other events leading to an accumulation of additional iron in the body; also, that iron accumulated as ferritin and hemosiderin in liver and spleen may not be readily available to restore blood hemoglobin concentrations on an acute basis.Acknowledgments. We gratefully acknowledge the technical assistance of Joan R. Moor and Lakshmi Vulimiri with these studies, and the support of Grants No. 17249 and HL22410 from the U.S. Public Health Service.     

Release of pre-absorbed cadmium from cultured cells by the addition of copper ion

Summary The biological interaction between cadmium and copper has been studied. Cadmium uptake of KB cells was specifically inhibited by the addition of copper ions to the culture medium. Cadmium which had already been taken up by the cells was released following the addition of copper ions.The authors are grateful to Dr. M. Ishizawa for his helpful discussion.     

Early effects of copper accumulation on methionine metabolism

Wilson's disease is characterized by longterm hepatic accumulation of copper leading to liver disease with reduction of S-adenosylmethionine synthesis. However, the initial changes in this pathway remain unknown and constitute the objective of the present study. Using the Long Evans Cinnamon rat model, early alterations were detected in the mRNA and protein levels, as well as in the activities of several enzymes of the methionine cycle. Notably, the main change was a redox-mediated 80% decrease in the mRNA levels of the methionine adenosyltransferase regulatory subunit as compared to the control group. Moreover, changes in S-adenosylmethionine, S-adenosylhomocysteine, methionine and glutathione levels were also observed. In addition, in vitro experiments show that copper affects the activity and folding of methionine adenosyltransferase catalytic subunits. Taken together, these observations indicate that early copper accumulation alters methionine metabolism with a pattern distinct from that described previously for other liver diseases.     

Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells

SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien). The copper-depleted neuroblastoma cell line obtained showed decreased activities of the copper enzymes Cu, Zn superoxide dismutase and cytochrome c oxidase with concomitant increases in reactive oxygen species. Mitochondrial antioxidants (Mn superoxide dismutase and Bcl-2) were up-regulated. Overexpression and activation of p53 were early responses, leading to an increase in p21. Eventually, copper-depleted cells detached from the monolayer and underwent apoptosis. Activation of up-stream caspase-9, but not caspase-8, suggested that apoptosis proceeds via a mitochondrial pathway, followed by caspase-3 activation. The addition of copper sulfate to the copper-depleted cells restored copper enzymes, normalized antioxidant levels and improved cell viability. We conclude that prolonged copper starvation in these replicating cells leads to mitochondrial damage and oxidative stress and ultimately, apoptosis.Received 24 April 2003; accepted 23 May 2003     

Cellular copper distribution: a mechanistic systems biology approach

Copper is an essential but potentially harmful trace element required in many enzymatic processes involving redox chemistry. Cellular copper homeostasis in mammals is predominantly maintained by regulating copper transport through the copper import CTR proteins and the copper exporters ATP7A and ATP7B. Once copper is imported into the cell, several pathways involving a number of copper proteins are responsible for trafficking it specifically where it is required for cellular life, thus avoiding the release of harmful free copper ions. In this study we review recent progress made in understanding the molecular mechanisms of copper transport in cells by analyzing structural features of copper proteins, their mode of interaction, and their thermodynamic and kinetic parameters, thus contributing to systems biology of copper within the cell.     

Structure and function of type I copper in multicopper oxidases

The type I copper center in multicopper oxidases is constructed from 1Cys2His and weakly coordinating 1Met or the non-coordinating 1Phe/1Leu, and it exhibits spectral properties and an alkaline transition similar to those of the blue copper center in blue copper proteins. Since the type I copper center in multicopper oxidases is deeply buried inside the protein molecule, electron transfers to and from type I copper are performed through specific pathways: the hydrogen bond between an amino acid located at the substrate binding site and a His residue coordinating type I copper, and the His-Cys-His sequence connecting the type I copper center and the trinuclear copper center comprised of a type II copper and a pair of type III coppers. The intramolecular electron transfer rates can be tuned by mutating the fourth ligand of type I copper. Further, mutation at the Cys ligand gives a vacant type I copper center and traps the reaction intermediate during the four-electron reduction of dioxygen.     

Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity

Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility, and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses. We demonstrate that Cys58 and at least three Glu surrounding residues surrounding it, are essential to efficiently bind copper. Moreover, copper binding promotes the TFF1 homodimerization, thus increasing its motogenic activity in in vitro wound healing assays. Copper levels could then modulate the TFF1 functions in the GI tract, as well as its postulated role in cancer progression and invasion.     

Cadmium-induced lipofuscins and effect of zinc on hepatopancreas cells inIdotea baltica

Histological investigation revealed cadmium-induced lipofuscin formation in hepatopancreatic cells of the crustacean isopod,Idotea baltica. A comparison of lipofuscin induction by cadmium and by copper showed that cadmium has a weaker peroxidative action than copper. The effect of cadmium was reduced by the simultaneous presence of zinc, which on its own was ineffective in lipofuscin induction. A tentative explantation of the interactive effects of these materials is suggested.     

Measuring cellulose decomposition using Benchkote-paper,for the estimation of soil pollution with copper

Summary Cellulose decomposition in paddy soil polluted by copper was determined by the use of polyethylene-backed absorbent paper (Benchkote) as a source of cellulose. It was shown that the paper is a suitable material for measuring the rate of cellulose decomposition. Correlations were found between copper content in the soil, the growth of rice plants and the cellulose decomposition rate.Acknowledgment. Gratitude is extend to Dr M.H. Martin, Department of Botany, University of Bristol, England, for suggesting the use of Benchkote paper.     

Permeability of fresh and stored human erthrocytes to glycerol and its acylated derivatives

The effect of copper ions on the permeation of glycerol and its mono-, di-, and triacetate derivatives was studied in fresh and stored erythrocytes. Permeability was unchanged with storage. Acylated glycerols permeate the cells mainly by non-facilitated mechanism, as their transport is almost unaffected by copper ions.     

Menkes disease

Menkes disease is caused by mutations in the copper-transporting P_1B-type ATPase ATP7A. ATP7A has a dual function: it serves to incorporate copper into copper-dependent enzymes, and it maintains intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics between different cellular locations depending on copper levels.The mechanism for sensing the concentration of copper, for trafficking, as well as the details of the mechanism of copper translocation across the membrane are unknown. Received 24 September 2007; received after revision 12 October 2007; accepted 17 October 2007     

Mapping the antigenicity of copper-treated cellular prion protein with the scrapie isoform

When recombinant and cellular prion protein (PrP(C)) binds copper, it acquires properties resembling the scrapie isoform (PrP(Sc)), namely protease resistance, detergent insolubility and increased beta sheet content. However, whether the conformations of PrP(C) induced by copper and PrP(Sc) are similar has not been studied in great detail. Here, we use a panel of seven monoclonal antibodies to decipher the epitopes on full-length mouse PrP(C) that are affected by exogenous copper, and to compare the antigenicity of the copper-treated full-length PrP(C) with the full-length PrP(Sc) present in scrapie-infected mouse brains. In the presence of copper, we found that epitopes along residues 115-130 and 153-165 become more accessible on PrP(C). These regions correspond to the two beta sheet strands in recombinant PrP and they were proposed to be important for prion conversion. However, when we compared the antibody-binding patterns between full-length PrP(C) with full-length PrP(Sc) and between copper-treated full-length PrP(C) with full-length PrP(Sc), antibody binding to residues 143-155 and 175-185 was consistently increased on PrP(Sc). Collectively, our results suggest that copper-treated full-length PrP(C) does not resemble full-length PrP(Sc), despite acquiring PrP(Sc)-like properties. In addition, since each full-length protein reacts distinctively to some of the antibodies, this binding pattern could discriminate between PrP(C) and PrP(Sc).     

铜合金三酸抛光微观效果研究

通过扫描电子显微镜微观观察的方法对三酸化学抛光液中各组分对铜合金表面抛光效果的影响进行了研究.结果表明,采用微观观察法能够更直观有效地研究各组分对铜合金表面抛光效果的影响,在此基础上,获得铜合金表面最佳抛光液:磷酸200~300ml/L、硫酸200~400ml/L(磷酸+硫酸500~600ml/L)、硝酸200~250ml/L(紫铜)、40~150ml/L(黄铜)、盐酸5~15ml/L.经处理的铜合金表面不仅外观光亮、微观平整,而且铜合金表面制备的转化膜中性盐雾测试时间更长、防腐性能更好.根据扫描电子显微镜观察铜合金微观形貌获得最佳抛光液组成的方法,简单方便、准确有效     

Zinc,copper and manganese levels in various tissues following fluoride administration

Summary Distribution of zinc, copper and manganese has been studied in liver, kidney and bone of rats subjected for 10 months to varied fluoride concentrations in drinking-water. In the liver a significant fall in the levels of Mn, Cu and Zn was registered. In the kidney, the Mn level fell whereas the zinc level increased. In the bone, the copper content fell, whereas the manganese content increased.     

Antioxidant and prooxidant roles of copper in Tween 20-induced hemolysis of hamster and pig erythrocytes containing marginal vitamin E

The concentration-dependent effects of copper acting either as an antioxidant or as a prooxidant were examined in vitro using Tween 20-induced hemolysis. When cupric ion concentration was more than 10 M, free copper(II) acted as a prooxidant; both extensive hemolysis and production of unknown thiobarbituric acid-reactive substance occurred in hamster and pig erythrocytes irrespective of vitamin E status. However, when cupric ion concentration was 2–4 M in the incubation medium, copper showed a clear antioxidant activity, reducing both hemolysis and malondialdehyde production induced either by diluted peroxide-containing Tween 20 with ascorbic acid and sodium azide in vitamin E-deficient hamster erythrocytes, or by peroxide-containing Tween 20 in pig erythrocytes containing marginal amounts of vitamin E. Copper(II) is taken up by the erythrocytes, where copper(I)-complexes may contribute to the protection of cells with membrane vitamin E against oxidative radical attack.