Effect Of Copper Deficiency Research Articles

The effect of copper deficiency on the formation of hemosiderin in sprague-dawley rats

We demonstrated previously that loading iron into ferritin via its own ferroxidase activity resulted in damage to the ferritin while ferritin loaded by ceruloplasmin, a copper-containing ferroxidase, was not damaged and had similar characteristics to native ferritin (Welch et al. (2001) Free Radic Biol Med 31:999-1006). Interestingly, it has been suggested that the formation of hemosiderin, a proposed degradation product of ferritin, is increased in animals deficient in copper. In this study, groups of rats were fed normal diets, copper deficient diets, iron supplemented diets, or copper deficient-iron supplemented diets for 60 days. Rats fed copper-deficient diets had no detectable active serum ceruloplasmin, which indicates that they were functionally copper deficient. There was a significant increase in the amount of iron in isolated hemosiderin fractions from the livers of copper-deficient rats, even more than that found in rats fed only an iron-supplemented diet. Histological analysis showed that copper-deficient rats had iron deposits (which are indicative of hemosiderin) in their hepatocytes and Kupffer cells, whereas rats fed diets sufficient in copper only had iron deposits in their Kupffer cells. Histologic evidence of iron deposition was more pronounced in rats fed diets that were deficient in copper. Additionally, sucrose density-gradient sedimentation profiles of ferritin loaded with iron in vitro via its own ferroxidase activity was found to have similarities to that of the sedimentation profile of the hemosiderin fraction from rat livers. The implications of these data for the possible mechanism of hemosiderin formation are discussed.

Effect of Copper Deficiency on Blood Lipid Profile and Haematological Parameters in Broilers

The aim of the study was to observe the changes in haematological parameters and blood lipid profile through copper (Cu) deficiency. Eighty broiler chicks were used in the study. The chicks were separated into two equal groups (n = 40), feed treatment according to the groups started on day 7. The animals in the control group were fed with normal feed. Those in the Cu-deficient group were fed with feed that did not contain supplemental Cu. Blood samples were taken from all the animals on days 7, 21 and 49. Fibrinogen and prothrombin time were assayed in plasma; total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-cholesterol), triglyceride and ceruloplasmin were assayed in sera; and haematocrit and thrombocyte levels were assayed in the blood samples. Total cholesterol, triglyceride and LDL-cholesterol levels were significantly higher in the Cu-deficient group than in the control group. Serum ceruloplasmin levels were lower in the Cu-deficient group than in the control group. Prothrombin time was higher in the Cu-deficient group than in the control group. Haematocrit levels were lower in the Cu-deficient group than in the control group. It was concluded that Cu deficiency created hypertriglyceridaemia, hypercholesterolaemia, insufficient growth and anaemia in broilers.

Atp7a determines a hierarchy of copper metabolism essential for notochord development

The critical developmental and genetic requirements of copper metabolism during embryogenesis are unknown. Utilizing a chemical genetic screen in zebrafish, we identified small molecules that perturb copper homeostasis. Our findings reveal a role for copper in notochord formation and demonstrate a hierarchy of copper metabolism within the embryo. To elucidate these observations, we interrogated a genetic screen for embryos phenocopied by copper deficiency, identifying calamity, a mutant defective in the zebrafish ortholog of the Menkes disease gene (atp7a). Copper metabolism in calamity is restored by human ATP7A, and transplantation experiments reveal that atp7a functions cell autonomously, findings with important therapeutic implications. The gene dosage of atp7a determines the sensitivity to copper deprivation, revealing that the observed developmental hierarchy of copper metabolism is informed by specific genetic factors. Our data provide insight into the developmental pathophysiology of copper metabolism and suggest that suboptimal copper metabolism may contribute to birth defects.

Decreased Hephaestin Activity in the Intestine of Copper-Deficient Mice Causes Systemic Iron Deficiency

Copper and iron metabolism intersect in mammals. Copper deficiency simultaneously leads to decreased iron levels in some tissues and iron deficiency anemia, whereas it results in iron overload in other tissues such as the intestine and liver. The copper requirement of the multicopper ferroxidases hephaestin and ceruloplasmin likely explains this link between copper and iron homeostasis in mammals. We investigated the effect of in vivo and in vitro copper deficiency on hephaestin (Heph) expression and activity. C57BL/6J mice were separated into 2 groups on the day of parturition. One group was fed a copper-deficient diet and another was fed a control diet for 6 wk. Copper-deficient mice had significantly lower hephaestin and ceruloplasmin (approximately 50% of controls) ferroxidase activity. Liver hepcidin expression was significantly downregulated by copper deficiency (approximately 60% of controls), and enterocyte mRNA and protein levels of ferroportin1 were increased to 2.5 and 10 times, respectively, relative to controls, by copper deficiency, indicating a systemic iron deficiency in the copper-deficient mice. Interestingly, hephaestin protein levels were significantly decreased to approximately 40% of control, suggesting that decreased enterocyte copper content leads to decreased hephaestin synthesis and/or stability. We also examined the effect of copper deficiency on hephaestin in vitro in the HT29 cell line and found dramatically decreased hephaestin synthesis and activity. Both in vivo and in vitro studies indicate that copper is required for the proper processing and/or stability of hephaestin.

Effects of copper deficiency on mouse yolk sac vasculature and expression of angiogenic mediators

Cu deficiency results in embryonic defects and yolk sac (YS) vasculature abnormalities. In diverse model systems, Cu treatment modulates angiogenesis, perhaps by influencing the activity of angiogenic mediators such as vascular endothelial growth factor (VEGF). Conversely, Cu chelators can suppress angiogenesis. Gestation day (GD) 8.5 embryos from mice fed Cu-adequate (Cu+) or Cu-deficient (Cu-) diets were cultured in Cu+ or Cu- medium for 48 hr. Growth and development were evaluated, and YS vessel diameters were measured. Using RT-PCR and immunohistochemistry, the mRNA and protein expressions of VEGF, Flt-1, Flk-1, Angiopoietin-1 (Ang-1), and Tie-2 were analyzed. Cu+/Cu+ embryos developed normally, whereas Cu-/Cu- embryos showed a high incidence of developmental anomalies. Cu-/Cu- YS had a high proportion of vessels that were large in diameter compared to the Cu+/Cu+ YS. The mRNA expression of angiogenic mediators in Cu-/Cu- YS was similar to that in Cu+/Cu+ YS. The protein expression of VEGF in the Cu-/Cu- YS without any vessel defects, and Tie-2 in the Cu-/Cu- YS with both vessel defects and blood islands was significantly lower than that in the Cu+/Cu+ YS. The protein expression of Flt-1, Flk-1 and Ang-1 was similar among groups regardless of the presence, or type, of vessel defects. Results from the current study support the concept that Cu is required for the normal development of YS vasculature. Our data suggest that the impaired vascularization of Cu-deficient YS cannot be explained fully by the altered protein expression of the angiogenic growth factors reported here.

Downregulation of myelination, energy, and translational genes in Menkes disease brain

Menkes disease (MD) is an X-linked recessive neurodegenerative disorder caused by mutations in a copper-transporting p-type ATPase (ATP7A) that normally delivers copper to the central nervous system. The precise reasons for neurodegeneration in MD are poorly understood. We hypothesized that gene expression changes in a MD patient with a lethal ATP7A mutation would indicate pathophysiological cascades relevant to the effects of copper deficiency in the developing brain. To test this hypothesis, oligonucleotide probes for 12,000 genes arrayed on Affymetrix Human Genome U95 GeneChips were used for expression profiling of fluorescently labeled primary cRNAs from post-mortem cerebral cortex and cerebellum of a MD patient who died at 6 months of age and a normal control brain matched for age, gender, and race. Histopathologic analysis of the proband’s brain showed preservation of neuronal integrity and no hypoxic effects. However, cerebrospinal fluid and brain copper levels were subnormal, and expression profiling identified over 350 known dysregulated genes. For a subset of genes (≈12%) analyzed by quantitative RT-PCR, the correct cross-validation rate was 88%. Thirty known genes were altered in both cortex and cerebellum. Downregulation of genes involved in myelination, energy metabolism, and translation was the major finding. The cerebellum was more sensitive to copper deficiency.

Micronutrient Changes in Some Tissues of Copper Deficient Rats

The present study was carried out to investigate the effect of copper deficiency on tissue level of some minerals (Na, K, Ca, P, Cu, Fe, Mg, Zn, Mn) in the growing male rats divided into two groups of rats fed either a copper deficient (0.06mgCu/Kg) or a Copper adequate diet. Both groups of rats were fed for six weeks. Copper deficiency decreased the final body weight of the rats by 21% compared to copper- adequate control rats. The haematological parameter i.e packed cell volume (PCV) and white blood cell (WBC) count of the copper deficient rats were significantly reduced compared to the control rats. Tissue content of nine elements (potassium, sodium, calcium, magnesium, manganese, copper, zinc, iron and phosphorus) were measured in the liver and the kidney of both group of rats. In copper deficiency, however, significant increase (p<0.05) in the tissue content of some elements (Zn, Ca, Fe, Na, K, Mn) were observed compared to the control, while Cu, Mg and phosphorus level were lowered compared to the control. The result implies that copper deficiency in rats could be detrimental to growth, mineral metabolism and hence the overall well being of the rat.

Copper in Drinking Water: Using Symptoms of Exposure to Define Safety

For the past five years, a team at the University of Chile’s Institute of Nutrition and Food Technology in Santiago, led by Magdalena Araya, has been assessing the response of healthy adults to varying concentrations of copper in drinking water. Their goal is to define safe limits for the early, acute effects of excessive copper exposure via drinking water. Their latest report verifies earlier findings that gastrointestinal symptoms such as nausea, abdominal pain, diarrhea, and vomiting occur when copper concentrations reach 4.0–6.0 milligrams per liter (mg/L) [EHP 112:1068–1073]. This provides the best confirmation to date that the World Health Organization’s (WHO) current drinking water limit for copper of 2.0 mg/L is reasonable. Copper is an essential nutrient needed to prevent anemia and keep the skeletal, reproductive, and nervous systems healthy. The U.S. National Research Council currently recommends that adults receive 1.5–3.0 mg of copper daily to prevent deficiencies. However, the health effects of high copper intake are poorly understood. Reports of copper poisoning are uncommon, and are linked to eating fruit sprayed with copper fungicides, cooking food in copper vessels, or ingesting grams of copper sulfate in suicide attempts. In such cases, copper toxicosis damages the liver and kidneys. The copper content of most of the world’s natural water supplies does not exceed more than a few milligrams per liter, although concentrations can be higher in well water and in hard water delivered through newly installed copper pipes. Araya and colleagues are working to identify markers of early biologically relevant effects of copper deficiency and excess. Past studies have shown that gastrointestinal symptoms are better indicators of acute exposure to copper than biochemical markers, such as blood copper, serum ceruloplasmin, and the activity of liver enzymes. According to Araya, copper absorption from food is unlikely to induce acute gastrointestinal responses, whereas the pH of water favors copper solubilization and absorption, which induce gastrointestinal effects. Therefore, it becomes important to define the copper concentrations in drinking water that cause gastrointestinal symptoms. The current randomized, double-blind, community-based study monitored 1,365 people from 441 families. The subjects ranged in age from 18 to 60 years. For two months each family’s drinking water was spiked with copper at concentrations of <0.01, 2.0, 4.0, or 6.0 mg/L. The lowest copper intake represented the concentration of copper in Santiago’s tap water. The higher concentrations reflected the WHO guidelines (2.0 mg/L) and levels noted in earlier studies to produce nausea (4.0 mg/L) and vomiting (6.0 mg/L). Participants were told to switch to plain tap water for 48 hours if they experienced any of a list of symptoms. If symptoms recurred after participants resumed drinking the copper-treated water, they were told to permanently switch back to plain water. Each household kept a daily diary of water consumption and symptoms. About 16% of the participants experienced at least one gastrointestinal symptom, with nausea and abdominal pain described most often. All dosage groups reported some symptoms, although the numbers in the two lowest-dosage groups were not statistically significant. Women reported two-thirds of the symptoms. They also appeared more sensitive to copper than men—for instance, during the first week, women’s symptoms occurred at 4.0 mg/L, compared to 6.0 mg/L for men. The team’s latest results confirm the findings from their earlier studies, which involved controlled clinical trials with smaller numbers of people. According to the authors, given the lack of statistically significant effects in the lower-dosage groups, the results support the WHO guideline of 2.0 mg/L copper in drinking water as a safe limit.

Increased Heme Oxygenase-1 Expression during Copper Deficiency in Rats Results from Increased Mitochondrial Generation of Hydrogen Peroxide

The activity of hepatic heme oxygenase (HO) in rats is elevated in response to copper deficiency. However, the mechanism responsible for the increase in HO activity is poorly understood. Oxidative stress is a common denominator for many of the signals that induce HO-1, the inducible isoform of HO. The present study evaluated the role of H(2)O(2) and the mitochondrial electron transport chain as a potential mechanism for the induction of HO-1 during copper deficiency. Mitochondria isolated from the livers of young male rats fed a copper-deficient diet for 5 wk had significantly (P < 0.05) reduced levels of NADH:cytochrome c reductase (31% reduction), succinate:cytrochrome c reductase (42% reduction), and cytochrome c oxidase (70% reduction) activities and significantly increased production of H(2)O(2) (48% increase) when glutamate was used as a substrate. Hepatic levels of HO-1 protein and mRNA were also significantly elevated (48 and 20%, respectively) in copper-deficient rats, indicating that copper deficiency stimulated the expression of the HO-1 gene. Furthermore, hepatic HO-1 protein content was best described by a regression model that included mitochondrial NADH:cytochrome c reductase and succinate:cytochrome c reductase activities, but not cytochrome c oxidase activity (R(2) = 0.54, P < 0.02). Hydrogen peroxide is a known inducer of HO-1, and our results suggest that increased mitochondrial H(2)O(2) production resulting from inhibition of respiratory complex activities contributes to the induction of HO-1 during copper deficiency. The levels of HO-1 protein and mRNA were also elevated (85 and 95%, respectively) in hearts from copper-deficient rats, indicating that the effects of copper deficiency on HO-1 gene expression are not limited to hepatic tissue.

Proinflammatory effects of copper deficiency on neutrophils and lung endothelial cells.

Dietary copper deficiency increases the accumulation of circulating neutrophils in the rat lung microcirculation. This process includes neutrophil adhesion to, migration along, and emigration though the vascular endothelium. The current study was designed to examine the role of copper in each of these steps. Neutrophils were isolated from rats fed either a copper-adequate (CuA, 6.1 microg Cu/g diet) or copper-deficient diet (CuD, 0.3 microg Cu/g diet) for 4 weeks. First, transient and firm adhesion of neutrophils to P-selectin in a flow chamber showed there were more adhered CuD neutrophils than CuA ones. This effect is probably caused by the increased expression of CD11b that was observed in the current study. Second, the evaluation of neutrophil migration under agarose showed that the CuD neutrophils moved farther than the CuA group in response to IL-8 but not fMLP; this suggests an increased sensitivity to a CD11/CD18-independent signalling pathway. Third, the contractile mechanism of endothelial cells was studied. Elevated F-actin formation in Cu-chelated lung microvascular endothelial cells suggests that neutrophil emigration may be promoted by enhanced cytoskeletal reorganization of the endothelium during copper deficiency. Combined, these results support the theory that dietary copper deficiency has proinflammatory effects on both neutrophils and the microvascular endothelium that promote neutrophil-endothelial interactions.

Carbohydrate metabolism in erythrocytes of copper deficient rats

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using 13C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD +. Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

DNA damage induced by copper deficiency in cattle assessed by the Comet assay

Cattle hypocuprosis is a well-known endemic disease in several parts of the world. In a previous paper, the clastogenic effect of copper deficiency in cattle has been described although the occurrence of DNA damage was not directly tested. For this reason, the relation between DNA damage assessed by the Comet assay and Cu plasma concentration was studied in Aberdeen Angus cattle. Blood samples were obtained in heparinized Vacutainer ® tubes from 28 female Aberdeen Angus cows during pregnancy or immediately after to give birth. Each sample was divided into two aliquots for Comet assay and Cu plasma determination, respectively. From the 28 cattle sampled, 17 were normocupremic and 11 were hypocupremic. Results obtained showed that whereas the average plasma Cu level in normocupremic cattle was 67.6 μg/dl, in hypocupremic cattle it was 32.1 μg/dl. The increase of DNA damage was mostly evidenced by the decrease of comet degree 1 cells and an increase of comet degree 2 cells. Correlation analysis comparing plasma Cu levels and degree 1 cells showed a correlation coefficient 0.72 ( P<0.01). The comparison between plasma Cu levels and comet degree 2 cells was −0.65 ( P<0.01). The comparison between plasma Cu levels and the comet length-head diameter medians determined in 23 out of 28 animals showed a correlation coefficient of −0.54 ( P<0.01). The induction of DNA damage was clearly supported by the fact that the decrease of plasma Cu levels was correlated with the increase of comet length-head diameter. These findings could be considered as a contribution to the hypothesis that DNA and chromosome damage are a consequence of the higher oxidative stress suffered by hypocupremic animals.

Augmented metalloproteinase activity and acute lung injury in copper-deficient rats.

Dietary copper is required for normal function of >30 mammalian enzyme systems. Copper deficiency causes a number of cardiovascular defects as well as impaired immune cell function. Little is known regarding the effects of copper deficiency on acute inflammatory responses, but this topic is relevant because many members of the Western population receive less than the recommended dietary allowance of copper. In the current studies, we investigated the effects of dietary copper deficiency on acute lung injury induced by intrapulmonary deposition of IgG immune complexes. Weanling male Long-Evans rats were fed diets either adequate (5.6 microg/g) or deficient (0.3 microg/g) in copper. IgG immune complex lung injury was greatly increased in copper-deficient rats as determined by lung vascular leakage of albumin and histopathology. However, no change was observed in either the lung content of tumor necrosis factor-alpha or lung neutrophil accumulation. Lungs from copper-deficient rats had much higher levels of matrix metalloproteinase (MMP)-2 and MMP-9 than did copper-adequate control animals. This increased activity was not attributable to alveolar macrophages or neutrophils. These data suggest that the augmented lung injury caused by copper deficiency is due to increased pulmonary MMP-2 and MMP-9 activity and not a generalized amplification of the inflammatory response.

Effect of copper deficiency on oxidative DNA damage in Jurkat T-lymphocytes

The micronutrient copper is a catalytic cofactor for copper, zinc superoxide dismutase and ceruloplasmin, which are two important antioxidant enzymes. As such, a lack of copper may promote oxidative stress and damage. The purpose of this study was to determine the effect of copper deficiency on oxidative damage to DNA in Jurkat T-lymphocytes. To induce copper deficiency, cells were incubated for 48 h with 5-20 μM 2,3,2-tetraamine (2,3,2-tet), a high affinity copper chelator. Such treatment did not affect cell proliferation/viability, as assessed by measuring mitochondrial reduction of WST-1 reagent (4-[3-(4-Iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate). Furthermore, the induction of copper deficiency did not promote oxidative DNA damage as evaluated by the comet assay. Comet scores were 15 ± 0 and 16 ± 1 for control and copper-deficient cells, respectively. However, the copper-deficient cells sustained greater oxidative DNA damage than the control cells (comet scores of 175 ± 15 and 50 ± 10, respectively) when both were oxidatively challenged with 50 μM hydrogen peroxide (H 2O 2). Supplemental copper but not zinc or iron prevented the potentiation of the H 2O 2-induced oxidative DNA damage caused by 2,3,2-tet. These data suggest that copper deficiency compromises the antioxidant defense system of cells, thereby increasing their susceptibility to oxidative DNA damage.

Clastogenic effect of copper deficiency in cattle

Copper plays an essential role as a micronutrient. Deficiency of this element (hypocuprosis) in experimental and domestic animals has a severe impact on growth as well as on reproduction. The occurrence of lesions during hypocuprosis is correlated with the depletion of an enzymatic group in which copper takes part. The aim of this work was to analyse chromosomal aberrations in Aberdeen Angus cows of the province of Buenos Aires in relation with the Cu plasma levels. Short term lymphocyte cultures were made from samples obtained from four groups of animals: two groups with normal levels of copper in plasma and two groups with severe hypocupremia. This analysis showed a significant increase of the frequency of chromosomal aberrations ( p<0.001) in the hypocupremic groups in relation with control groups. Finally, the Spearman correlation analysis showed a significant negative association ( p<0.05) between copper levels and the yield of chromosomal aberrations. The increase of the frequencies of chromosomal aberrations found in the hypocupremic groups could be explained by the higher oxidative stress suffered by these animals. A lower catalytic activity of enzymes such as Cu/Zn superoxide dismutase (Cu/Zn-SOD) and cytochrome- c oxidase could increase the intracellular production of active oxygen species (O 2 −, H 2O 2 and OH o) with the consequent clastogenic effects.

Adverse developmental and reproductive effects of copper deficiency in Xenopus laevis.

The effect of copper (Cu) deficiency on the reproduction and development in Xenopus laevis was evaluated, culminating in the development of a defined concentration-response relationship. Separate groups of four adult frog pairs were fed one of three diets for 28 d: (1) low-copper (-Cu); (2) copper supplemented (+Cu); and (3) ASTM standard beef liver and lung (BLL). Embryos collected from frogs administered the -Cu diet had markedly decreased egg masses and viability rates and an increased rate of necrosis when compared to the other dietary treatments. Malformations in -Cu larvae included maldevelopment of the heart, eye, craniofacial region, brain, and notochord. Larvae from adults administered the -Cu diet showed delayed abnormal hindlimb development, characterized as selective reductive deficiencies distal to the femur, with poor cartilaginous development. A U-shaped dose-response curve characteristic of nutritional essentiality was developed for Cu. Overall, these studies indicated that embryos produced from frogs administered a -Cu diet are substantially less viable than embryos from frogs administered a +Cu or copper-adequate (BLL) diet.

Folate and homocysteine metabolism in copper-deficient rats

To investigate the effect of copper deficiency on folate and homocysteine metabolism, we measured plasma, red-cell and hepatic folate, plasma homocysteine and vitamin B-12 concentrations, and hepatic methionine synthase activities in rats. Two groups of male Sprague–Dawley rats were fed semi-purified diets containing either 0.1 mg (copper-deficient group) or 9.2 mg (control group) of copper per kg. After 6 weeks of dietary treatment, copper deficiency was established as evidenced by markedly decreased plasma and hepatic copper concentrations in rats fed the low-copper diet. Plasma, red-cell, hepatic folate, and plasma vitamin B-12 concentrations were similar in both groups, whereas plasma homocysteine concentrations in the copper-deficient group were significantly higher than in the control group ( P<0.05). Copper deficiency resulted in a 21% reduction in hepatic methionine synthase activity as compared to the control group ( P<0.01). This change most likely caused the increased hepatic 5-methyltetrahydrofolate and plasma homocysteine concentrations in the copper-deficient group. Our results indicate that hepatic methionine synthase may be a cuproenzyme, and plasma homocysteine concentrations are influenced by copper nutriture in rats. These data support the concept that copper deficiency can be a risk factor for cardiovascular disease.

Effects of copper deficiency on the magnetic response of La1.85Sr0.15Cu1−εO4+δ

In this article we study the magnetic behavior of a series of copper-deficient spin-glass compounds La1.85Sr0.15Cu1−εO4−δ. High-quality ceramic samples were prepared by a sol–gel technique. Stoichiometry and structural characterization of the specimens were verified by x-ray diffraction, inductively coupled plasma spectrometry, atomic absorption spectrophotometry, and thermogravimetric analysis. Low-field ac and dc magnetic measurements, carried out in a superconducting quantum interference device magnetometer for samples with ε=0.05, 0.15, and 0.25, revealed all major characteristics of a spin-glass system: thermal irreversibility, magnetic remanence, time-relaxation and frequency-dependent ac susceptibility.

Copper and signal transduction: platelets as a model to determine the role of copper in stimulus-response coupling.

Platelets from copper-deficient rats have been used as a model to investigate the role of copper in receptor-mediated cellular responses. Copper deficiency doubles the rate of dense granule secretion and increases myosin association with the platelet cytoskeleton following thrombin stimulation. Mechanisms underlying the effects of copper deficiency on thrombin-induced signals that elicit dense granule secretion involve suppression of protein kinase C activity and impairment of Ca2+ release from intracellular stores. Copper deficiency also reduces the cellular GTP content of platelets. This may limit receptor effector coupling through GTP-dependent regulatory proteins leading to protein kinase C activation and the release of Ca2+ from intracellular stores. The reduction in GTP content during copper deficiency results from its utilization to maintain cellular ATP levels in response to severely inhibited cytochrome c oxidase activity in platelet mitochondria. Thus, the role of copper in maintaining normal signal transduction may be indirectly related to its biological function in mitochondria.

Effects of copper deficiency on the structure and microwave properties of YBa2Cu3O7−δ films deposited by laser ablation

The work reported here evaluated the correlation between the copper composition and the structural and microwave properties of YBa2Cu3O7−δ (YBCO) films deposited on MgO substrates. Detailed x-ray diffraction measurements revealed that the superconducting YBCO phase in the films has a solubility range on the copper-poor composition side. The structure of the YBCO phase depends on copper composition: a lower copper composition is associated with a larger c-axis lattice constant and a decreased degree of orthorhombicity. These structural changes correlated well with increases in normal resistivity, decreases of transition temperature Tc, and increases in microwave surface resistance Rs. The films with less copper composition also show a more gradual decrease in Rs below Tc than do copper-rich films. These results suggest that changes in these properties are closely connected with copper deficiency that can occur more easily when the copper composition is low. The copper composition is, therefore, a crucial factor in developing YBCO films with low microwave loss.