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At least 649 records · Page 36Linked to original sources
PubMed2005

A novel copper-binding fold for the periplasmic copper resistance protein CusF.

We have determined the crystal structure of apo-CusF, a periplasmic protein involved in copper and silver resistance in Escherichia coli. The protein forms a five-stranded beta-barrel, classified as an OB-fold, which is a unique topology for a copper-binding protein. NMR chemical shift mapping experiments suggest that Cu(I) is bound by conserved residues H36, M47, and M49 located in beta-strands 2 and 3. These residues are clustered at one end of the beta-barrel, and their side chains are oriented toward the interior of the barrel. Cu(I) can be modeled into the apo-CusF structure with only minimal structural changes using H36, M47, and M49 as ligands. The unique structure and metal binding site of CusF are distinct from those of previously characterized copper-binding proteins.

Amino Acid Sequence↗
PubMed2006

A comparative study of the binding and inhibition of four copper-containing amine oxidases by azide: implications for the role of copper during the oxidative half-reaction.

Copper amine oxidases (CuAOs) catalyze the oxidative deamination of primary amines operating through a ping-pong bi-bi mechanism. In this work, azide (an exogenous monodentate ligand) was used to probe the role of copper during the oxidative half-reaction of CuAO catalysis. The effects of azide on both the reductive and oxidative half-reactions of pea seedling amine oxidase (PSAO), the recombinant human kidney diamine oxidase (rhDAO), Arthrobacter globiformis amine oxidase (AGAO), and Pichia pastoris amine oxidase (PPLO) have been examined. For the reductive half-reaction, defined as the oxidation of amine substrate to an aldehyde, azide was discovered to exhibit either noncompetitive or competitive inhibition with respect to the amine, depending on the enzyme source. With regard to the oxidative half-reaction, defined as the reoxidation of the enzyme via reduction of O(2) to H(2)O(2), azide has been determined to exhibit competitive inhibition with respect to O(2) in PSAO with a calculated K(i) value that is in excellent agreement with the experimentally determined K(d) value for the Cu(II)-N(3)(-) complex. Azide was found to exhibit mixed-type/partially competitive inhibition with respect to substrate O(2) in rhDAO, with an apparent K(i) that is similar to the K(d) value for the Cu(II)-N(3)(-) complex. The competitive inhibition for PSAO and the partially competitive inhibition for rhDAO are consistent with O(2) interacting directly with copper during enzymatic reoxidation. For the enzymes AGAO and PPLO, pure noncompetitive and mixed-type/partially competitive inhibition is observed. K(i) values for reductive and oxidative half-reactions are equivalent and are lower than measured K(d) values for the Cu(II)-N(3)(-) complexes in oxidized and substrate-reduced forms of these enzymes. Given these observations, it appears that substantial inhibition of the reductive half-reaction occurs at the concentrations of azide used for the oxidative half-reaction experiments, thereby complicating kinetic interpretation. At this time, the data do not permit us to distinguish between two possibilities: (1) inhibition by azide with respect to O(2) is intrinsically competitive in CuAOs, but this effect cannot always be deconvolved experimentally from the effects of azide on the reductive half-reaction; or (2) CuAOs differ in some steps of their reoxidation mechanisms.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development.

The trace metal copper (Cu) plays an essential role in biology as a cofactor for many enzymes that include Cu, Zn superoxide dismutase, cytochrome oxidase, ceruloplasmin, lysyl oxidase, and dopamine beta-hydroxylase. Consequently, Cu transport at the cell surface and the delivery of Cu to intracellular compartments are critical events for a wide variety of biological processes. The components that orchestrate intracellular Cu trafficking and their roles in Cu homeostasis have been elucidated by the studies of model microorganisms and by the characterizations of molecular basis of Cu-related genetic diseases, including Menkes disease and Wilson disease. However, little is known about the mechanisms for Cu uptake at the plasma membrane and the consequences of defects in this process in mammals. Here, we show that the mouse Ctr1 gene encodes a component of the Cu transport machinery and that mice heterozygous for Ctr1 exhibit tissue-specific defects in copper accumulation and in the activities of copper-dependent enzymes. Mice completely deficient for Ctr1 exhibit profound growth and developmental defects and die in utero in mid-gestation. These results demonstrate a crucial role for Cu acquisition through the Ctr1 transporter for mammalian Cu homeostasis and embryonic development.

Animals↗
PubMed1995

Evaluation of copper sulfate and a copper lysine complex as growth promoters for weanling swine.

Two 5-wk trials using 176 weanling pigs (average initial weight of 8.3 kg and age of 31 d) were conducted to examine the effect of feeding varying levels of dietary Cu from copper sulfate (CuSO4) or a copper lysine complex (CuLys) on performance, mineral stores, serum copper, and serum mitogenic activity. Dietary treatments were 0 (15 mg/kg of Cu in basal diet), 100, 150, or 200 mg/kg of supplemental Cu from CuSO4 or CuLys. Average daily gain and ADFI increased linearly (P < .01) with increasing dietary levels of Cu during wk 1 to 2, 3 to 5, and 1 to 5, with no difference (P > .10) between the Cu sources. Overall gain:feed ratios were not consistently affected by Cu source. Dietary Cu linearly increased liver, kidney (P < .001), and brain (P < .05) concentrations of Cu. In the liver, the linear response to supplemental Cu differed between Cu sources (P < .001); pigs fed 200 mg/kg of Cu from CuLys had the highest concentration of Cu. Serum Cu concentrations increased linearly during wk 1 to 2 (P < .01), 3 to 5, and 1 to 5 (P < .001), with no difference (P > .10) between sources. Serum mitogenic activity increased linearly during wk 1 to 2 and 1 to 5 (P < .05). Growth performance was linearly improved as the dietary level of Cu increased from 15 to 200 mg/kg, with similar responses for both Cu sources. Serum and tissue concentrations of Cu were generally equally affected by the two Cu sources, except liver Cu concentration, which was onefold higher for pigs fed 200 mg/kg of Cu as CuLys.

Aging↗
PubMed1981

[The clinical efficacy of the copper-containing intrauterine devices Nova T and Copper-T-200 Ag in a randomized study (author's transl)].

In a randomized study the clinical efficacy of the traditional intrauterine device. Copper-T-200 Ag was compared with the recently developed model Nova T. Altogether 93 women with regular menstrual cycles were examined; 45 women had a Nova T inserted and 48 the traditional Copper-T-200 Ag. The biosocial data of the women in the two groups did not differ from one another. No pregnancies occurred in either group within the first 12 months. Expulsion occurred in 2 women with Nova T and removal of the device had to be undertaken for bleeding and pain in 3 women with a Copper-T-200 Ag. At 12 months the two models did not differ in the number of recorded incidents. The reliability of randomized studies is discussed, as well as problems arising from the fact that the mode of insertion is not identical with both devices and requires practice in the case of the new model.

Female↗
PubMed1978

[Copper intra-uterine devices (I.U.D.) and pregnancy: a study of the metabolism of copper and of ceruloplasmin in the mother and in the products of conception (author's transl)].

The authors studied the variations in levels of copper and ceruloplasmin in the mother and in products of conception during the first trimester of pregnancy, during the 4th month of pregnancy and near term, having a series of 12 pregnancies with the copper I.U.D. in position. No change was observed between the levels of copper and ceruloplasmin in comparison with a control series.

Abortion, Induced↗
PubMed1983

Copper and copper-binding protein in fibrolamellar liver cell carcinoma.

Analysis of tissue from a recent case of fibrolamellar liver cell carcinoma by several staining and spectrophotometric methods demonstrated elevated copper and copper-binding protein (CBP) in malignant hepatocytes. Production of CBP has not previously been described for this or any other type of hepatocellular carcinoma. Identification of CBP in liver cell carcinoma adds further evidence that this protein is a normal synthetic product of liver cells which may reappear in chronic cholestasis or hepatic malignancy. The mechanism of disturbed copper homeostasis in this case is uncertain.

Adolescent↗
PubMed1977

Treatment of rheumatoid and degenerative diseases with copper complexes: a review with emphasis on copper-salicylate.

This review presents a historical account of the treatment of rheumatoid and other degenerative diseases with copper complexes. Clinical data obtained from 1940 to 1971 are provided for about 1,500 patients with rheumatoid arthritis (acute or chronic), rheumatic fever, ankylosing spondylitis, staphlococcal spondylitis, gonococcal arthritis, chronic gouty arthritis, polyarticular synovitis, coxitis, disseminated spondylitis, arthritis with psoriasis, Reiter's syndrome, lupus erythematosus, sarcoidosis, arthrosis deformans, erythema nodosum, sciatica (with and without lumbar involvement), cervical spine-shoulder syndrome or lumbar spine syndrome. The drugs used in these studies were Dicuprene, Alcuprin, Cuprimyl, and Permalon, a copper-salicylate preparation. A detailed presentation of toxicities associated with the use of these copper complexes is included.

Anti-Inflammatory Agents↗
PubMed1981

Effects of copper on the sabellid polychaete, Eudistylia vancouveri. II. Copper accumulation and tissue injury in the branchial crown.

Copper in seawater caused injury to the radioles (gills) of the sabellid polychaete, Eudistylia vancouveri. Light and electron microscopy showed the loss of cellular adhesion and the structural derangement that lead to cell necrosis and death. The progression of injury was related to the uptake of copper into the tissues. Copper was found by X-ray microanalysis to be localized subcellularly in membrane-bound vesicles that are similar to lysosomes. Cell breakdown may result from lysosomal labilization.

Animals↗
PubMed1992

The effect of time of introduction of a high-fructose, low-copper diet on copper deficiency in male rats.

The purpose of the present study was to compare the time of introduction of the high-fructose low-copper diet on the expression of copper (Cu) deficiency. Weanling male rats were randomly assigned to either a diet containing 62.7% fructose or starch, and 6.0 (F+Cu) or 0.6 (S-Cu) microgram Cu/g diet, respectively, for either 1, 2, or 3 wk before being transferred to a diet containing fructose and inadequate in copper (F-Cu). At week 10, body weight and relative heart size of rats initially consuming the F + Cu diet was inversely related to the week placed on the F-Cu diet, but not for those initially consuming S-Cu. Hematocrit, hepatic Cu concentration and RBC superoxide dismutase activity were significantly lower in rats initially consuming S-Cu when compared to those fed F + Cu. Mortality was greatest in rats switched to the F-Cu diet at weeks 1 and 2 when compared to those switched at week 3 regardless of the type of diet initially consumed. Plasma cholesterol, triacylglycerols, and blood urea nitrogen concentrations were not significantly altered by the type of diet initially consumed or by the time of introduction of the F-Cu diet. It was concluded that changing rats to a F-Cu diet at 1, 2, or 3 wk after weaning did not significantly improve some of the characteristic signs associated with Cu deficiency, but the later that the F-Cu diet was introduced after weaning the greater the chances for survival.

Aging↗
PubMed1996

Effect of zinc supplementation on metallothionein, copper, and zinc concentration in various tissues of copper-loaded rats.

The present study was designed to investigate the effects of Zn administration on metallothionein concentrations in the liver, kidney, and intestine of copper-loaded rats. Male CD rats were fed a diet containing 12 mg Cu and 67 mg Zn/kg body wt. They were divided into either acute or chronic experimental protocols. Rats undergoing acute experiments received daily ip injections of either Cu (3 mg/kg body wt) or Zn (10 mg/kg body wt) for 3 d. Chronic experiments were carried out on rats receiving Cu ip injections on d 1, 2, 3, 10, 17, and 24, Cu injections plus a Zn-supplemented diet containing 5 g Zn/kg solid diet, or a Zn-supplemented diet alone. Rats injected Zn or Cu had increased MT concentrations in liver and kidney. Zn produced the most important effects and the liver was the most responsive organ. Rats fed a Zn-supplemented diet had significantly higher MT concentrations in liver and intestine with respect to controls. Increased MT synthesis in the liver may contribute to copper detoxification; the hypothesis of copper entrapment in enterocytes cannot be confirmed.

Animals↗
PubMed2006

Copper-1,10-phenanthroline-induced apoptosis in liver carcinoma Bel-7402 cells associates with copper overload, reactive oxygen species production, glutathione depletion and oxidative DNA damage.

The mechanism of cytotoxicity on liver carcinoma Bel-7402 cells induced by copper-1,10-phenanthroline, Cu(OP)2, has been studied. Cell viability and apoptotic rate were examined in cells treated with Cu(OP)2 or Cu2+ alone. It was found that the apoptosis induced by Cu(OP)2 could not be induced by Cu2+ or OP alone in our experimental conditions. Total copper content in cells was measured by atomic absorption spectrophotometry, and the abnormal elevation of intracellular copper transported by lipophilic OP ligand may play the role of initial factor in the apoptosis, which caused subsequent redox state changes in cells. Intracellular levels of reactive oxygen species (ROS) were detected by fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA). Reduced (GSH) and total glutathione (GSSG + GSH) were determined by High-performance liquid chromatography (HPLC) after derivatization, and the ratios of GSH/GSSG were subsequently calculated. The overproduction of ROS and the decreased GSH/GSSG ratio were observed in cells which represented the occurrence of oxidative stress in the apoptosis. Oxidative DNA damage was also found in cells treated with Cu(OP)2 in the early stage of the apoptosis, and it suggests that the activation of DNA repair system may be involved in the pathway of the apoptosis induced by Cu(OP)2.

Apoptosis↗
PubMed1986

Purification of human copper, zinc superoxide dismutase by copper chelate affinity chromatography.

Copper, zinc superoxide dismutase was isolated from human red blood cell hemolysate by DEAE-Sepharose and copper chelate affinity chromatography. Enzyme preparations had specific activities ranging from 3400 to 3800 U/mg and recoveries were approximately 60% of the enzyme activity in the lysate. Copper chelate affinity chromatography resulted in a purification factor of about 60-fold. The homogeneity of the superoxide dismutase preparation was analyzed by sodium dodecyl sulfate-gel electrophoresis, analytical gel filtration chromatography, and isoelectric focusing.

Chelating Agents↗
PubMed1979

Copper allergy and copper IUD.

Epicutaneous tests with copper, nickel and cobalt were performed in 37 patients using copper IUD who had shown side-effects to the IUD. None of them was allergic to copper; four were allergic to nickel and one to cobalt. Metal allergy was not considered to be the cause of the side-effects in any of the patients.

Adult↗
PubMed1986

Induction of hepatocytes in the pancreas of copper-depleted rats following copper repletion.

Pancreatic hepatocytes are induced in rats maintained on copper-deficient diet containing 0.6% D-penicillamine for 8-10 weeks, followed by copper repletion. These induced hepatocytes are morphologically and functionally very similar to parenchymal cells of the liver. Immunofluorescence stains demonstrated the presence of albumin and catalase in these cells. Stains for pancreatic enzymes and hormones were negative. As expected, the hypolipidemic compound, ciprofibrate, induced peroxisome proliferation in these cells. These results indicate that a simple depletion and repletion of copper can trigger transdifferentiation in the pancreas of adult rats.

Albumins↗
PubMed1989

Effects of natural exposure to copper and zinc on egg size and larval copper tolerance in white sucker (Catostomus commersoni).

Sucker eggs were collected from a metal-contaminated site where previous collections had documented a maternal yolk factor associated with an increased larval copper tolerance during yolk nutrition. In this study, white sucker eggs were divided into groups which were water hardened and/or incubated at the contaminated site or a reference (control) site. Incubation at the contaminated site was associated with a decreased egg size and an increased deformity rate, but had no effect on fertilization rate or larval size. Incubation in contaminated streams increased the larval whole-body metal content, and decreased the tolerance and resistance of larvae exposed to copper in laboratory bioassays. An increase in water temperature accelerated the developmental rate of the larvae, but had no detectable effect on copper tolerance. Although metals did enter the eggs during water hardening, there was no difference in egg metallothionein content, and the lack of obvious hepatic activity until several days after hatching may prevent the formation of protective proteins. The authors hypothesize that the transfer of metals to white sucker eggs in association with yolk precursors, and the subsequent mobilization of these metals during yolk utilization, can account for the observed differences in larval tolerance and growth.

Abnormalities, Drug-Induced↗
PubMed1984

The copper-enzyme dopamine beta-monooxygenase: studies on the ability of several metals to inhibit the enzyme activity and to replace the copper.

The ability of several metals to inhibit dopamine beta-monooxygenase was measured and compared with their ability to compete with the binding of 64Cu to the water-soluble form of the bovine adrenal enzyme at pH 6.0. In the presence of an optimal concentration of copper (0.5 microM in the present assay system), an inhibition was observed upon addition of Hg(II), Zn(II), or Ni(II). Only a small fraction of the inhibition with these metals may be due to uncoupling of electron transport from hydroxylation. Preincubation of these metals with the Cu-depleted apoenzyme before addition of copper, revealed a stronger inhibition than if copper was added before the other metals. Hg(II), Zn(II), and Ni(II) also compete with the binding of 64Cu(II) to the protein. Hg(II) was the most effective and Ni(II) the least effective of these metals, both with respect to inhibition of the enzyme activity and to prevent the binding of 64Cu(II). Competition experiments on the binding of Zn(II) and 64Cu in the presence and absence of ascorbate, indicated i) a similar affinity of Cu(I) and Cu(II) to the native enzyme, and ii) a more rapid binding of Cu(I) than Cu(II) to the Cu-depleted and Zn-containing enzyme. Al(III), Fe(II), Mg(II), Mn(II), Co(II), Cd(II), and Pb(II) neither inhibited the enzyme activity nor competed with the binding of 64Cu(II) to the protein (Fe(II) was not tested for binding). Of those metals cited above only Cu(II)/Cu(I) was able to reactivate the apoenzyme.

Adrenal Glands↗
PubMed1989

Subcellular distribution of copper in the kidneys of normal, copper-poisoned, and thiomolybdate-treated sheep.

Twenty-seven sheep given either copper (Cu) and/or tetrathiomolybdate (TM) were used to study the subcellular distribution of Cu within the kidney and to monitor the location of lysosomes within the subcellular fractions using acid phosphatase (AP) as a marker enzyme. Copper dosing alone increased the Cu content in the liver and the kidneys. The administration of intravenous TM prevented the development of chronic copper poisoning (CCP) in sheep, reduced the rate of accumulation of Cu in the liver of Cu-dosed animals, but increased the Cu content of kidneys in both the control and Cu-dosed sheep. The total amount of Cu that accumulated in the kidneys of sheep given TM appears to depend on several factors: a) liver Cu concentration, b) Cu intake, and c) dosage of TM. Thus, the highest Cu concentration was found in the kidneys of sheep that continued to receive Cu orally at the same time as they were given TM. The intracellular distribution of Cu and AP in the kidneys showed that in the control sheep given neither Cu or TM, the highest proportion of Cu was in the cytosol fraction, and the highest specific activity of AP was in the light mitochondrial (lysosomal) fraction. Dosing with Cu markedly increased the Cu concentration and greatly elevated the total activity of AP in the heavier fractions, i.e., the nuclear (N) and heavy mitochondrial (MH). Thus, the increase in Cu observed in the N and MH fractions was not caused by an accumulation of Cu by nuclei and mitochondria, but was due to an accumulation of Cu by lysosomes that sedimented with the heavier fractions. The intracellular distribution of Cu in the kidneys of TM-treated sheep was similar to that seen in Cu-loaded sheep. Although Cu accumulated readily in the kidneys of animals receiving TM, kidney function tests showed neither glomerular nor tubular functional impairment.

Acid Phosphatase↗