Increased Copper Levels Research Articles

Copper kinetics and internal distribution in the marbled crayfish (Procambarus sp.)

Metal pollution e.g. copper, in water bodies occurs worldwide. Although copper is an essential trace metal, at certain levels it is still considered as pollutant. The aim of this study was to investigate the effect of exposure concentration on copper bioaccumulation in marbled crayfish (Procambarus sp.) by determining uptake and elimination kinetics. Crayfish were exposed to sub-lethal copper concentrations (average measured concentrations of 0.031 and 0.38mgCuL−1) for 14d and transferred to copper-free water for another 14d. At different time points during the uptake and elimination phases copper concentrations were measured in five organs (exoskeleton, gills, muscle, ovaries and hepatopancreas). At 0.031mgCuL−1, copper levels in the crayfish organs were not significantly increased compared to the control animals, suggesting effective regulation. Exposure to 0.38mgCuL−1 did lead to not significantly increased copper levels in muscles and ovaries, while the gills and exoskeleton, which are in direct contact with the water, showed significantly higher copper concentrations. In these four organs, copper showed fast uptake kinetics with equilibrium reached within 10d of exposure. Copper accumulation was highest in the hepatopancreas; uptake in this storage organ steadily increased with time and did not reach equilibrium within the 14-d exposure period. Copper accumulation levels in the marbled crayfish found in this study were hepatopancreas>gills>exoskeleton>muscle.

Effects of arbuscular mycorrhizal inoculation on metallophyte and agricultural plants growing at increasing copper levels

A pot culture experiment was carried out to assay the behavior of different arbuscular mycorrhizal (AM) fungal inocula on plant growth and copper (Cu) uptake using two metallophytes (Oenothera picensis and Imperata condensata) and one agricultural plant (Helianthus annuus) grown at increasing Cu supply levels. Plants were established in a Cu polluted soil spiked with 0, 150, 300 or 450mg Cukg−1, and inoculated or not with: (i) Cu-adapted AM fungi (GA) or (ii) the Cu non-adapted strain Glomus claroideum (GC). Differences in plant biomass between inoculated and uninoculated plants were found, which were dependent on the AM fungal inocula used and the Cu level applied. Although the beneficial effect of AM fungi in promoting plant biomass production was not observed in metallophytes plants, a positive interaction between GA and H. annuus increased the shoot growth, especially at higher Cu levels. In addition, the Cu transfer from the roots to the shoots was low, remaining mostly at root level, especially in non-mycorrhizal plants; however AM fungi produced changes in Cu distribution increasing the translocation to the shoots. Differences in AM fungal parameters (root colonization, spore number and glomalin production) were strictly dependent on the Cu level and the AM fungal inoculum, suggesting the existence of certain compatibility, which was dependent on the particular combination AM-plant used. Specifically, the glomalin accumulation and Cu-bound to glomalin were significantly higher in AM colonized H. annuus plants, which could suggest a highly efficient way to reduce the Cu toxicity levels in soil. Therefore the use of H. annuus with AM fungal could promote phytostabilization processes.

Changes on proline, phenolics compounds and antioxidants status in Euglena gracilis exposed to copper

The effects of copper toxicity on the content of bioactive compounds in Euglena gracilis were investigated using two CuSO4 concentrations (0.4 and 0.8 mM) added in medium culture. Proline, phenolic compounds and antioxidant activity were measured after 72 h of copper stress. Results obtained in this study show that increasing levels of copper (0.4 and 0.8 mM) resulted in a general increased proline, total phenolic compound and antioxidant activity in the cells of E. gracilis exposed to doses of 0.4 mM Cu 2+ in contrast one decreased significantly was observed when the doses was increasing to 0.8 mM with respect to control. These changes suggesting that the phenolic contents and the presence of proline as well as the synergistic effects among them affect the total antioxidant capacity of E. gracilis. Finally, these results provide useful and important information for researchers in order to increase the studies about antioxidant capacity and functional value of E. gracilis for bioremediation programs. Such information can be used to closely scrutinize the strategy of bioremediation programs for selecting E. gracilis strain for targeted biotechnologies purposes.

Altered Copper Level and Renal Dysfunction in Nigerian Women Using Skin-Whitening Agents

The purpose of the study was to determine the concentration of trace elements in serum samples of women who are chronic users of skin-whitening agents as well as the hepatic and renal effects of these agents on these women. The study was conducted among 23 skin-whitening users while 25 women served as the controls. The serum concentrations of Zn, Mn, and Mg were not significantly changed in these women compared with controls (p > 0.05), but Cu was significantly increased in skin-whitening agent users compared with controls (p < 0.05). Serum urea and creatinine were significantly increased compared with the controls (p < 0.05). Moreover, ALT, AST, albumin, total protein, and bilirubin were not significantly changed (p > 0.05). The significant increase in the levels of renal indices shows that these agents might be nephrotoxic after prolonged usage while increase in copper level with accompanying renal dysfunction may be an indication that copper mediates in oxidative-induced renal dysfunction. However, further study is needed to identify the cause and source of high serum copper as many of the herbal extracts may be rich sources of copper. Moreover, a large population study may be necessary to examine the exact correlation between copper and renal indices.

The ADP-ribosylation factor 1 (Arf1) is involved in regulating copper uptake

Copper is a cofactor for many essential enzymes in aerobic organisms. When intracellular copper levels are elevated, the Menkes (ATP7A) P-Type ATPase traffics from the trans-Golgi network (TGN) towards the plasma membrane to facilitate copper efflux. The ADP-ribosylation factor 1 (Arf1) is required for maintenance of Golgi architecture and for vesicular trafficking, including the copper-responsive trafficking of ATP7A. Here we report an ATP7A-independent role of Arf1 in copper homeostasis. Whilst the loss of ATP7A function increased copper levels, RNA interference mediated Arf1 knockdown reduced copper accumulation in HeLa cells as well as in both wild-type and ATP7A-null cultured fibroblasts. Arf1 therefore affected copper levels independently of ATP7A mediated copper efflux. Knockdown of Arf79F, the Drosophila melanogasterArf1 orthologue, also reduced copper accumulation in cultured Drosophila S2 cells, indicating an evolutionarily conserved role for this protein in cellular copper homeostasis. Whereas severe Arf1 inhibition with brefeldin A caused fragmentation and dispersal of the TGN resident protein Golgin 97, the peri-nuclear localisation of the Golgin 97 was retained following Arf1 knockdown, consistent with a moderate reduction in Arf1 activity. Ctr1 levels at the plasma membrane of cultured fibroblast cells were reduced following Arf1 knockdown, indicating an Arf1-dependent trafficking pathway is required for correct distribution of this copper uptake protein. Arf1-dependent trafficking pathways are therefore required for optimal copper uptake efficiency in cultured human and Drosophila cells.

Effects of small increases in copper levels on culturable basidiomycetous yeasts in low-nutrient soils

Investigating the effect of perturbations, with relatively low Cu concentrations, on yeast community composition in low-nutrient virgin soil. Culturable soil yeast populations were monitored at an experimental site treated with the fungicide copper oxychloride (10 mg Cu per kg soil). Yeast numbers were unaffected by additional Cu; however, a shift in yeast community composition from Hymenomycetes to Urediniomycetes species occurred. Subsequent growth experiments conducted with a synthetic liquid medium revealed that hymenomycetous and urediniomycetous yeasts were affected differently by 1 and 10 mg l(-1) Cu. Soil microcosm experiments then indicated that additional 10 mg kg(-1) Cu may improve the competitive ability of urediniomycetous yeasts in the presence of hymenomycetous yeasts. The shift from hymenomycetous to urediniomycetous yeasts, as a result of slightly increased soil Cu levels, may be because of hymenomycetous yeasts being more sensitive to elevated Cu levels and urediniomycetous yeasts having an improved competitive ability in the presence of elevated Cu levels. Yeast community composition of pristine low-nutrient soils may change as a result of perturbations with relatively low concentrations of Cu. Urediniomycetous yeasts should be studied as potential bio-indicators of Cu perturbations.

Regulation of copper transport in Arabidopsis thaliana: a biochemical oscillator?

Plants are among the most versatile higher eukaryotes in accommodating environmental copper availability to largely variable demands. In particular, copper deficiency in soils is a threat for plant survival since it mostly affects reproductive structures. One of the strategies that plant cells use to overcome this situation is to increase copper levels by expressing high-affinity copper transporters delivering the metal to the cytosol. In this minireview, we discuss recent advances in the structure, function, and regulation of the CTR/COPT family of copper transporters, and pay special attention to the Arabidopsis thaliana counterparts. These are constituted by transmembrane polypeptides, containing several copper-binding sequences of functional and/or regulatory value, and assembling as trimers. Copper deficiency activates the expression of some members of the COPT family via the interaction of the SPL7 transcription factor with reiterative GTAC motifs present in their promoters. Interestingly, the regulation of the synthesis of these transporters by copper itself constitutes a negative-feedback loop that could cause a sustained oscillation in the cytosolic copper levels. We analyze the theoretical conditions required for this hypothetical copper oscillation and the potential advantages of synchronization with other cycles. Diverse data in other organisms point to the relationship between copper homeostasis and circadian cycles.

Physiological adaptations in the lichens Peltigera rufescens and Cladina arbuscula var. mitis, and the moss Racomitrium lanuginosum to copper-rich substrate

Two lichen species ( Peltigera rufescens and Cladina arbuscula subsp. mitis) and one moss species ( Racomitrium lanuginosum) growing on a copper mine heaps (probably 200–300 yr old) in the village of Špania dolina (Slovak Republic) were assessed for selected physiological parameters, including composition of assimilation pigments, chlorophyll a fluorescence, soluble proteins and free amino acid content. The lichen C. arbuscula subsp. mitis was collected also at a control locality where total copper concentration in the soil was approximately 3% that of the waste heaps. Concentrations of Al, Co, Cu, Ni, Sb and Zn were highest in thalli of Peltigera, while the moss Racomitrium contained the highest content of Fe and Pb. Thalli of Cladina contained less metals than the cyanolichen Peltigera, and except for Zn metal concentrations in Cladina from the control locality were lower than in thalli of the same species from copper mine heaps. Regardless of the species or locality, the composition of assimilation pigments and chlorophyll a fluorescence showed that the tested lichens and moss were in good physiological condition and adapted to increased copper levels in the soil. There were significantly different amounts of total free amino acids in Peltigera, Cladina and Racomitrium from the Cu-polluted field. However, differences in amount of free amino acids in control, as well as Cu-polluted thalli of Cladina were less pronounced.

Effects of N-Acetylcysteine, Deferoxamine and Selenium on Doxorubicin-Induced Hepatotoxicity

The aims of our study were to evaluate the antioxidant defence mechanisms of liver tissue challenged by doxorubucin (DOX) and to compare the possible protective effects of N-acetylcysteine (NAC) (n=10), deferoxamine (DOF) (n=10), DOF+NAC (n= 10) and selenium (n=9) on doxorubicin-induced hepatotoxicity. Fifty-six male rats (Mean weight = 250 ± 50 g) randomly divided into five groups. Animals in study groups were pretreated with a single dose of Dox, which was administered intravenously. Control group (n=7) was treated with intravenous saline injection. Selenium was given intraperitoneally. Blood and urine samples were collected before sacrifice. Liver tissue samples were collected and tissue superoxide dismutase (SOD), glutathione peroxidase (GSH-px), CAT activity, MDA, Zn, iron and copper were determined. DFO decreased lipid peroxidation significantly. DFO and NAC decreased CAT activity significantly. Antioxidant regimes increase SOD activities significantly. DOF and NAC increase GSH-px activities and copper levels significantly. Beneficial effect of selenium seems to result from its stimulation of SOD but not to GSH-px. It has been found that DOF, NAC and selenium have protective effects on Dox-induced hepatocellular damage. DOF+NAC did not result additional benefit.

A Multicopper Oxidase (Cj1516) and a CopA Homologue (Cj1161) Are Major Components of the Copper Homeostasis System of Campylobacter jejuni

Metal ion homeostasis mechanisms in the food-borne human pathogen Campylobacter jejuni are poorly understood. The Cj1516 gene product is homologous to the multicopper oxidase CueO, which is known to contribute to copper tolerance in Escherichia coli. Here we show, by optical absorbance and electron paramagnetic resonance spectroscopy, that purified recombinant Cj1516 contains both T1 and trinuclear copper centers, which are characteristic of multicopper oxidases. Inductively coupled plasma mass spectrometry revealed that the protein contained approximately six copper atoms per polypeptide. The presence of an N-terminal "twin arginine" signal sequence suggested a periplasmic location for Cj1516, which was confirmed by the presence of p-phenylenediamine (p-PD) oxidase activity in periplasmic fractions of wild-type but not Cj1516 mutant cells. Kinetic studies showed that the pure protein exhibited p-PD, ferroxidase, and cuprous oxidase activities and was able to oxidize an analogue of the bacterial siderophore anthrachelin (3,4-dihydroxybenzoate), although no iron uptake impairment was observed in a Cj1516 mutant. However, this mutant was very sensitive to increased copper levels in minimal media, suggesting a role in copper tolerance. This was supported by increased expression of the Cj1516 gene in copper-rich media. A mutation in a second gene, the Cj1161c gene, encoding a putative CopA homologue, was also found to result in copper hypersensitivity, and a Cj1516 Cj1161c double mutant was found to be more copper sensitive than either single mutant. These observations and the apparent lack of alternative copper tolerance systems suggest that Cj1516 (CueO) and Cj1161 (CopA) are major proteins involved in copper homeostasis in C. jejuni.

Response to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency

HomeHypertensionVol. 52, No. 3Response to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency Shahar Lavi and Amir Lerman Shahar LaviShahar Lavi Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn Search for more papers by this author and Amir LermanAmir Lerman Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn Search for more papers by this author Originally published28 Jul 2008https://doi.org/10.1161/HYPERTENSIONAHA.108.116475Hypertension. 2008;52:e28Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 28, 2008: Previous Version 1 We appreciate Klevay’s comments1 regarding the potential role of copper supplement for the treatment of endothelial dysfunction. Our study focused on the association among coronary endothelial dysfunction, local bioavailability of NO, and local reactive oxygen species generation.2 We demonstrated that, in patients with endothelial dysfunction, there is increased local ROS generation, reduced activity of antioxidants (superoxide dismutase) and preserved production of NO. However, there was no significant difference in the arterial levels of either isoprostanes or superoxide dismutase between patients with coronary endothelial dysfunction and patients with normal response to acetylcholine. The relationship among copper deficiency, isoprostanes, superoxide dismutase, and arterial response to acetylcholine3 is indeed very intriguing. Thus, it may be speculated that the relative deficiency of copper as a central molecule in the antioxidant axis may play a role in the mechanism of endothelial dysfunction.It should be noted that, although copper deficiency may have adverse effects on the cardiovascular system, high copper levels are associated with increased risk of death from cardiovascular disease. In fact, even the second quartile of copper was associated with a trend toward increased risk compared with the lowest quartile (hazard ratio: 1.84).4 Increased copper levels were also an independent predictor for acute myocardial infarction.5The use of copper in medicine dates to Hippocrates, but there are not much data to support its use in cardiovascular disease. The effect of antioxidants on endothelial function should be studied. Copper, an antioxidant nutrient, would be a potential agent.Sources of FundingThis study was supported by NIH grants K24, HL-69840, and R01 HL-63911 and the Mayo Foundation.DisclosuresNone.1 Klevay LM. Endothelial dysfunction, isoprostanes, and copper deficiency. Hypertension. 2008; 52: e27.LinkGoogle Scholar2 Lavi S, Yang EH, Prasad A, Mathew V, Barsness GW, Rihal CS, Lerman LO, Lerman A. The interaction between coronary endothelial dysfunction, local oxidative stress, and endogenous nitric oxide in humans. Hypertension. 2008; 51: 127–133.LinkGoogle Scholar3 Lynch SM, Frei B, Morrow JD, Roberts LJ II, Xu A, Jackson T, Reyna R, Klevay LM, Vita JA, Keaney JF Jr. Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation. Arterioscler Thromb Vasc Biol. 1997; 17: 2975–2981.CrossrefMedlineGoogle Scholar4 Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol. 2000; 151: 1182–1188.CrossrefMedlineGoogle Scholar5 Salonen JT, Salonen R, Korpela H, Suntioinen S, Tuomilehto J. Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland. Am J Epidemiol. 1991; 134: 268–276.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Suliburska J, Bogdański P, Pupek-Musialik D and Krejpcio Z (2010) Dietary Intake and Serum and Hair Concentrations of Minerals and their Relationship with Serum Lipids and Glucose Levels in Hypertensive and Obese Patients with Insulin Resistance, Biological Trace Element Research, 10.1007/s12011-010-8650-0, 139:2, (137-150), Online publication date: 1-Feb-2011. September 2008Vol 52, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.108.116475 Originally publishedJuly 28, 2008 PDF download Advertisement SubjectsHypertension

ATP7B Copper-Regulated Traffic and Association With the Tight Junctions: Copper Excretion Into the Bile

The copper transporter ATP7B plays a central role in the elimination of excess copper by the liver into the bile, yet the site of its action remains controversial. The studies reported here examine the correspondence between the site of ATP7B action and distribution and the pathways of copper disposal by the liver. Microscopy and cell fractionation studies of polarized Can 10 cells forming long-branched bile canaliculi have been used to study the cellular distribution of ATP7B. Copper excretion into the bile was studied in perfused rat liver. Copper excess provokes a massive download of the ATP7B retained in the trans-Golgi network into the bile canalicular membrane. Furthermore, a stable ATP7B pool is localized to the tight junctions that seal the bile canaliculi. The profile of Cu(64) excretion into the bile by isolated rat livers perfused under one-pass conditions provides evidence of copper excretion by 2 separate mechanisms, transcytosis across the hepatocyte and paracellular transport throughout the tight junctions. Whereas the ATP7B retained in the trans-Golgi-network is massively translocated to the bile canalicular membrane in response to increased copper levels, a pool of ATP7B associated with the tight junctions remains stable. In situ studies indicate that copper is excreted into the bile by 2 separate pathways. The results are discussed in the frame of the normal and impeded excretion of copper into the bile.

Correlation between birth weight, leptin, zinc and copper levels in maternal and cord blood

Leptin and zinc are involved in the regulation of appetite. Copper is a trace element regulating the functions of several cuproenzymes that are essential for life. To evaluate the relationship between zinc and copper status and the leptin system in humans, we examined whether leptin concentrations in the mother and the newborn correlate with the weight of mother, placenta and newborn. A total of 88 pregnant women at 38-42 weeks' gestation were studied. All infants were categorized as small for gestational age (SGA) (n = 16), average for gestational age (AGA) (n = 59) or large for gestational age (LGA) (n = 13). Leptin, zinc, and copper levels were measured in maternal and cord serum at birth. Maternal BMI and placental weight of the LGA groups were significantly higher than those of the SGA and AGA groups. Cord and maternal leptin levels of the SGA groups were significantly lower than those of the AGA and LGA groups. Maternal serum leptin levels were positively correlated with BMI and maternal zinc levels in all groups. Cord serum leptin levels of all groups were positively correlated with birth weight and placental weight. Birth weight was negatively correlated with maternal and cord copper level of all groups. Umbilical leptin concentrations of SGA newborns correlated with leptin concentrations of their mothers. In all pregnancies, birth weight increases in association with increase in cord leptin level. Our results suggest that maternal zinc but not copper level has an effect on maternal serum leptin levels. The increase in copper level in both maternal and cord blood may contribute to restriction in fetal growth.

Serum antioxidant micromineral (Cu, Zn, Fe) status of drug dependent subjects: Influence of illicit drugs and lifestyle

BackgroundUse of illicit drugs induces multiple nutrient deficiencies. Drug habit, sexual practice and socioeconomic factors influence the nutrient profile of drug dependent subjects. The literature on this issue is still insufficient. This study has tested the hypothesis that illicit drug use and lifestyle impair mineral status. To test this hypothesis, 253 men multiple drug users of age 18–45 years were recruited to investigate their serum copper, zinc and iron levels. Influence of illicit drugs and their lifestyle on the mineral levels was also examined. The study subjects were drug dependent who had shared needles and had sexual activity with multiple partners. Serum concentrations of the minerals were estimated by atomic absorption flame spectrometry.ResultsResults showed a significant increase in serum copper and zinc concentrations, and decrease in iron level in drug dependent subjects. The increase of copper level was found to be much higher than that of zinc. Period of drug abuse had made a significant positive influence on the copper and iron levels, but it was apparently reversed for zinc concentration. Multiple sexual partnerships had significant influence on zinc status. There also were significant relationships observed between body mass index (BMI) as well as certain socioeconomic factors, and mineral status of drug dependent subjects and non-drug dependent controls. A series of multiple linear regression analysis predicted mineral values for education, age and BMI. The group (drug dependent subject = 1, non-drug dependent control = 2) had a significant influence on these parameters. However, after controlling these factors, it was shown that illicit drug use significantly contributed to influence the serum mineral levels.ConclusionIllicit drug use impairs serum mineral value causing an increase in copper and zinc and a decrease in iron. Lifestyle and nutritional status of drug dependent subjects influence serum mineral concentrations.

ADMINISTRATION OF METHAMPHETAMINE AFFECTS SERUM LEVELS OF TRACE ELEMENTS IN RATS

Methamphetamine (MA) is a well-known street drug of abuse and neurotoxin that may cause long-lasting changes in the dopaminergic pathways of central nervous system. The formation of toxic reactive oxygen species has been implicated in MA-neurotoxicity. Trace elements are structural or regulatory components of many enzymes and proteins acting in antioxidant system. Their status can by attenuated by oxygen species generated during MA administration. In this study, MA (1 mg/kg/day) was subcutaneously injected into male Wistar rats (n = 24) for 8 weeks. Normal saline was similarly injected for the same period to control group (n= 16). The rats were locally bred and maintained on the standard laboratory pellet diet. All rats were anesthetized and samples of blood were collected directly from the heart. We determined manganese and selenium using GF-AAS and copper and zinc using flame AAS in serum of rats. The body weight of animals after 8 weeks of MA administration decreased from 490±44.9 g (mean±SD) to 447± 31.5 g. Serum manganese levels were 3.6±1.18 μg/L in the control and 2.9±0.74 μg/L in the experimental group. Selenium level showed a significant decrease in the MA rats from mean control level of 367±22.9 μg/L to 330±34.8 μg/L. The admistration of MA reduced zinc concentration from 20.1±2.21 mmol/L to 17.6±mmol/L in serum of rats but increased copper concentration from 14.8± 2.25mmol/L to 17.5± 2.65mmol/L. MA toxicity is probably attenuated by antioxidant system in which some trace elements play important role. Thus, their consumption in organism during MA administration is elevated. On the contrary, increased copper level in MA group can be attributed to the more cellular damage accompanied with MA intake.

A note on copper bioaccumulation in Mozambique tilapia, Oreochromis mossambicus (Osteichthyes: Cichlidae)

Copper (Cu) is one of the most commonly reported metal pollutants in African water bodies, but there are few studies on African freshwater fish species of copper accumulation and copper toxicity. Adult O. mossambicus were exposed to 0mg l−1 (control) and 0.75mg l−1 Cu for 96h and 0 (control), 0.11, 0.29 and 0.47mg l−1 copper for 64 days. Samples of liver and gills were collected after 96h, and after 1, 32 and 64 days, respectively. There were significant differences in the mean Cu accumulation values in the liver and gills between the control and the Cu-exposed fish after the 96-h exposure. In fish exposed to 0.11 and 0.29mg l−1 Cu for 64 days there was an increase in copper level in the tissues. In fish exposed to 0.47mg l−1 Cu the concentration in the gill and liver tissue did not increase between Day 1 and Day 32. At this time, Cu accumulation in the liver was higher than for fish exposed to 0.11 and 0.29mg l−1 Cu for 64 days. Exposure to approximately 0.47mg l−1 Cu for more than 32 days induced mortality.

Alloying with copper to reduce metal dusting of nickel

AbstractCopper is thought to be noncatalytic to carbon deposition from gas atmospheres, and owing to its extremely low solubility for carbon, inert to the metal dusting reaction. Thus, the addition of copper to nickel, which forms a near perfect solid solution, may be able to suppress or greatly retard the metal dusting of the alloy, without the need for a protective oxide scale on the surface.The dusting behaviour of Ni‐Cu alloys containing up to 50 wt% Cu, along with pure Cu, was investigated in a 68%CO‐31%H2‐1%H2O gas mixture (aC: 19) at 680°C for up to 150 h. Surface analysis showed that two types of carbon deposits, graphite particle clusters and filaments, were observed on pure Ni and Ni‐Cu alloys with Cu contents of up to 5 wt%. Alloys with more than 10 wt% Cu showed very little coking, forming filaments only. SEM and TEM analyses revealed metal particles encapsulated by graphite shells within the graphite particle clusters, and metal particles at filament tips or embedded along their lengths. A kinetic investigation showed that alloy dusting rates decreased significantly with increasing copper levels up to 10 wt%. At copper concentrations of more than 20 wt%, the rate of metal dusting was negligible. Although pure copper is not catalytic to carbon formation, scattered carbon nanotubes were observed on its surface. The effect of copper on alloy dusting rates is attributed to a dilution effect.

Increased copper level in oral mucosal tissue of patients with submucous fibrosis and who chew areca nut products

Increased copper level in oral mucosal tissue of patients with submucous fibrosis and who chew areca nut products

Clioquinol Mediates Copper Uptake and Counteracts Copper Efflux Activities of the Amyloid Precursor Protein of Alzheimer's Disease

The key protein in Alzheimer's disease, the amyloid precursor protein (APP), is a ubiquitously expressed copper-binding glycoprotein that gives rise to the Abeta amyloid peptide. Whereas overexpression of APP results in significantly reduced brain copper levels in three different lines of transgenic mice, knock-out animals revealed increased copper levels. A provoked rise in peripheral levels of copper reduced concentrations of soluble amyloid peptides and resulted in fewer pathogenic Abeta plaques. Contradictory evidence has been provided by the efficacy of copper chelation treatment with the drug clioquinol. Using a yeast model system, we show that adding clioquinol to the yeast culture medium drastically increased the intracellular copper concentration but there was no significant effect observed on zinc levels. This finding suggests that clioquinol can act therapeutically by changing the distribution of copper or facilitating copper uptake rather than by decreasing copper levels. The overexpression of the human APP or APLP2 extracellular domains but not the extracellular domain of APLP1 decreased intracellular copper levels. The expression of a mutant APP deficient for copper binding increased intracellular copper levels several-fold. These data uncover a novel biological function for APP and APLP2 in copper efflux and provide a new conceptual framework for the formerly diverging theories of copper supplementation and chelation in the treatment of Alzheimer's disease.

Iron deficiency in the pregnant rat has differential effects on maternal and fetal copper levels

Iron deficiency during pregnancy causes problems both for the mother and fetus. Iron deficiency is known to have secondary effects on copper metabolism. In this study, we use a rat model to examine the effect of iron deficiency on copper levels in maternal and fetal tissue. We assess whether the effects of iron deficiency on copper metabolism are due to alterations in mRNA levels of proteins of copper transport. Rowett Hooded Lister rats were fed diets with four different iron contents before and during pregnancy. Maternal and fetal samples were collected on day 21 of gestation. Copper and iron levels of liver and placenta were analyzed, mRNA levels of genes involved in copper transport were studied, and copper oxidase activity measured. Reduced dietary iron was found to increase maternal liver copper, inversely correlating with iron levels. Correspondingly, copper and ceruloplasmin increased in maternal serum. The placenta showed the greatest increase in copper levels. As the iron content of the maternal diet decreased so did the iron and copper levels in the fetal liver. In all tissues examined, mRNA expression for CTR1, ATOX1, ATP7A, and ATP7B was unchanged by iron deficiency. However, copper oxidase activity in maternal serum and placenta was increased. Our study in a rat model demonstrates that iron deficiency during pregnancy has a differential effect on copper metabolism in the mother and fetus. It is clear from this study that the changes in copper levels that accompany iron deficiency are not mediated by changes in transcription of the genes involved in copper transport.