scholarly journals Comparison of pathways of copper metabolism in aorta and liver. A functional test of metallothionein

1982 ◽  
Vol 204 (2) ◽  
pp. 541-548 ◽  
Author(s):  
J E Balthrop ◽  
C T Dameron ◽  
E D Harris

Soluble fractions from chick liver and aorta were examined for copper-binding proteins. In liver a zinc-binding thionein appeared to be the major binding protein for copper. Aortic tissue contained only traces of this thionein protein. Unlike liver, moderate amounts of soluble copper in aorta showed no association with macromolecules. Chicks fed on copper-deficient diets for 8 days had one-third the liver copper concentrations of controls. Aortic copper concentration was decreased only slightly, but the activity of lysyl oxidase, a copper-dependent enzyme in aorta, was decreased significantly. Treating the deficient chicks with CuSO4 (1 mg/kg) restored liver copper rapidly. The increase correlated with the binding of copper to a 10 000-mol.wt. component in the soluble fraction. Aortic copper concentrations responded much less to the CuSO4 treatment, but lysyl oxidase activity was again measurable in the tissue. Radioactive isotopes of copper bound almost exclusively to the 10 000-mol.wt. component in liver and to components of mol.wt. 30 000 or above in aorta. Hardly any of the administered radioactivity appeared with the 10 000-mol.wt. components in aorta, and none was found with unbound copper. The 30 000-mol.wt. components in aorta showed superoxide dismutase activity that was sensitive to NaCN. They also showed the highest specific activity of copper of any other aorta component. A clear distinction was seen between the metabolism of copper in liver and aortic tissues. Whereas a copper thionein, metallothionein, was a major component in the liver pathway, it is doubtful that this protein plays a major role in the intracellular metabolism of copper in aortic tissue.

1980 ◽  
Vol 58 (4) ◽  
pp. 609-613 ◽  
Author(s):  
P. E. Fletcher ◽  
G. L. Fletcher

Zinc- and copper-binding proteins were isolated from the plasma of winter flounder using gel filtration chromatography. A single copper-binding protein fraction of molecular weight 170 000 was isolated from the plasma of both sexes.In male and female flounder over 95% of the plasma zinc was associated with a zinc-binding protein(s) with a molecular weight of 76 000. In male flounder the remaining zinc appeared to be bound to a protein(s) of molecular weight 186 000. In female flounder the remaining 5% of the zinc was associated with two zinc-binding fractions with apparent molecular weights of 186 000 and 340 000 – 370 000.Extracts of plasma vitellogenin and egg yolk proteins revealed significant quantities of zinc and copper. It is hypothesized that the female specific zinc-binding protein (340 000 – 370 000) was vitellogenin.


2018 ◽  
Vol 48 ◽  
pp. 1860103 ◽  
Author(s):  
A. Andrighetto ◽  
F. Borgna ◽  
M. Ballan ◽  
S. Corradetti ◽  
E. Vettorato ◽  
...  

The ISOLPHARM project explores the feasibility of exploiting an innovative technology to produce extremely high specific activity beta-emitting radionuclides as radiopharmaceutical precursors. This technique is expected to produce radiopharmaceuticals that are virtually mainly impossible to obtain in standard production facilities, at lower cost and with less environmental impact than traditional techniques. The groundbreaking ISOLPHARM method investigated in this project has been granted an international patent (INFN). As a component of the SPES (Selective Production of Exotic Species) project at the Istituto Nazionale di Fisica Nucleare–Laboratori Nazionali di Legnaro (INFN–LNL), a new facility will produce radioactive ion beams of neutron-rich nuclei with high purity and a mass range of 80–160 amu. The radioactive isotopes will result from nuclear reactions induced by accelerating 40 MeV protons in a cyclotron to collide on a target of UC[Formula: see text]. The uranium in the target material will be [Formula: see text]U, yielding radioactive isotopes that belong to elements with an atomic number between 28 and 57. Isotope separation on line (ISOL) is adopted in the ISOLPHARM project to obtain pure isobaric beams for radiopharmaceutical applications, with no isotopic contaminations in the beam or subsequent trapping substrate. Isobaric contaminations may potentially affect radiochemical and radionuclide purity, but proper methods to separate chemically different elements can be developed.


Blood ◽  
1948 ◽  
Vol 3 (12) ◽  
pp. 1472-1477 ◽  
Author(s):  
F. H. L. TAYLOR ◽  
S. M. LEVENSON ◽  
M. A. ADAMS ◽  
MARY KENDRICK

Abstract 1. Phosphate exchange in red cells and plasma was studied in vitro using P32 in the form of sodium phosphate as a tracer. 2. No phosphate was added other than the isotopic preparation which was of high specific activity. 3. Inorganic phosphate exchanged freely between the plasma and the erythrocytes at 37.5 C. in a period of four hours. Minimal transfer occurred at 7 C. 4. Most of the added P32 which passed into the erythrocytes during this time remained in the inorganic fraction, less than 15 per cent being found in the organic acid soluble fraction. 5. The specific activity of the inorganic phosphate of the erythrocytes was equal to or greater than that obtaining for the inorganic phosphate of the plasma at the end of the four hour incubation period at 37.5 C.


Author(s):  
G.А. Zhorov ◽  
◽  
L.L. Zakharova ◽  
V.N. Obryvin ◽  
◽  
...  

For correctly assess the effectiveness and safety of the use of sorption-detoxifying agents and feed additives intended for animals receiving feed with an excess content of toxicants, it is necessary to take into account the background levels of radionuclides, toxic elements, pesticides and other technogenic and natural pollutants in the studied substances. The need for such studies is due both to the existence of areas with a naturally elevated level of natural toxicants in the sources of raw materials for the production of additives and drugs, and to the increasing anthropogenic influence, accompanied by the entry of xenobiotics into environmental objects. In series of radiometric studies, the specific activity of technogenic and natural radioactive isotopes (90Sr, 137Cs, 40К, 226Ra, 232Th) in a number of sorption-detoxifying and biologically active substances and preparations used in animal husbandry and veterinary medicine as part of feed additives and pharmacological agents was determined. It was found that in 43% of the studied samples, the level of specific activity of 1,1Sr in 3-90 times higher than allowed by the current standards. The maximum level of 90Sr, equal to (137±9) Bq/kg, was detected in perlite. The specific activity of 137Cs did not exceed the permissible level: in mineral sorbents its amount reached (40±7) Bq/kg, in organic and complex sorbents – (24±4), and in feed additives – (29±8) Bq/kg. The maximum levels of 40K were (1429±83) Bq/ kg in minerals (radionite) and (2613±100) Bq/kg in organic substances (lignohumate). The levels of 226Ra and 232Th did not exceed (153±13) and (79±13) Bq/kg, respectively, and were higher in the mineral samples.


2019 ◽  
Vol 63 (3) ◽  
pp. 349-364 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Sylvie Ricard-Blum

Abstract The lysyl oxidase family comprises five members in mammals, lysyl oxidase (LOX) and four lysyl oxidase like proteins (LOXL1-4). They are copper amine oxidases with a highly conserved catalytic domain, a lysine tyrosylquinone cofactor, and a conserved copper-binding site. They catalyze the first step of the covalent cross-linking of the extracellular matrix (ECM) proteins collagens and elastin, which contribute to ECM stiffness and mechanical properties. The role of LOX and LOXL2 in fibrosis, tumorigenesis, and metastasis, including changes in their expression level and their regulation of cell signaling pathways, have been extensively reviewed, and both enzymes have been identified as therapeutic targets. We review here the molecular features and three-dimensional structure/models of LOX and LOXLs, their role in ECM cross-linking, and the regulation of their cross-linking activity by ECM proteins, proteoglycans, and by inhibitors. We also make an overview of the major ECM cross-links, because they are the ultimate molecular readouts of LOX/LOXL activity in tissues. The recent 3D model of LOX, which recapitulates its known structural and biochemical features, will be useful to decipher the molecular mechanisms of LOX interaction with its various substrates, and to design substrate-specific inhibitors, which are potential antifibrotic and antitumor drugs.


1987 ◽  
Vol 44 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Darrel Jon Laurén ◽  
D. G. McDonald

Whole body, gill, and liver copper uptake, gill Na+-K+-ATPase specific activity, and gill and liver acid-soluble thiols (AST), glutathione, and cysteine of rainbow trout (Salmo gairdneri) were measured during 28 d of exposure to 55 μg copper∙L−1. Na+-K+-ATPase specific activity was inhibited by 33% within 24 h of copper exposure, but this was compensated by a significant increase in microsomal protein so that the total Na+-K+-ATPase activity per milligram of gill tissue returned to normal by day 14. There was no accumulation of copper and no increase in AST, glutathione, or cysteine in the gill. However, after 7 d of exposure, hepatic AST and glutathione had increased by about 2 times, and a sulfhydryl-rich, acid-soluble protein, tentatively identified as metallothionein, increased by 2.8 times. Copper accumulation was highest in the liver, but other tissues also accumulated copper.


1979 ◽  
Vol 180 (3) ◽  
pp. 605-612 ◽  
Author(s):  
J R Mann ◽  
J Camakaris ◽  
D M Danks ◽  
E G Walliczek

Copper therapy was applied to brindled mouse mutants, which suffer from lethal hypocupraemia, by using cuprous and cupric solutions. The method of treatment was a single subcutaneous injection of 50 microgram of copper at 7 days of age. Early effects of the dose were: prevention of the tremors and spasms seen in untreated mutants, raising to normal and near-normal of caeruloplasmin oxidase and lysyl oxidase activities and pigmentation of skin and fur. Growth of mutants was retarded up to 23 days of age, but thereafter they rapidly gained weight to be nearly normal by 60 days of age. At 3 days after injection, copper concentrations in previously deficient mutant organs apart from liver were at least as much as those of treated normals, which had remained unchanged. Copper in mutant livers had increased only slightly in comparison with the normal control. A state of copper deficiency recurred in mutant tissues by 25 days after injection. A solution of Cu+, retained as such by an alkyl polyether, and sebacic acid resulted in greater growth rates after 23 days than did three other copper treatments. Cu+ may have resulted in an improved growth response owing to it being more readily metabolized than C12+. Delayed release of copper from the site of injection may have played an important role.


1967 ◽  
Vol 18 (1) ◽  
pp. 169 ◽  
Author(s):  
GI Alexander ◽  
JM Harvey ◽  
JH Lee ◽  
WC Stubbs

Four experiments described determined the effect of copper and cobalt therapy on the growth and productivity of cattle on the marine plains of central coastal Queensland. Copper was administered by subcutaneous injections of copper glycinate, and cobalt by dosing per os with heavy cobalt pellets. The growth of weaned cattle was significantly improved by copper, particularly from June to October when limited palatable feed on the high ground forced the animals to forage on the para grass swamps. During the same period, 2-year-old heifers also showed a growth response to copper. Their conception rate increased after 19 months of copper therapy but not after 10.5 months. The growth rate of their calves bas significantly increased by copper supplementation. Liver copper concentrations were always low in untreated cattle. Copper therapy maintained these reserves at higher levels, which varied according to the season and the rate of growth of the animals. Calves born to treated cows had higher initial liver copper reserves than those from untreated cows, but in the absence of copper therapy these reserves declined to low and comparable levels in all calves at weaning. Pasture analyses suggest that the copper deficiency revealed was due to interference with copper metabolism rather than to a low copper status in the diet; this interference did not appear to be due to molybdenum. Weaned cattle appeared to respond to cobalt during 1960 but not subsequently, while the cows and calves showed no response. The vitamin B12 status in liver and serum appeared adequate in both treated and untreated cattle.


1963 ◽  
Vol 41 (1) ◽  
pp. 9-18 ◽  
Author(s):  
A. T. Matheson

Two types of intracellular aminopeptidase activity are present in E. coli B. One type, present in the 'soluble' fraction, is completely inactivated by chymotrypsin or trypsin; the other, in the particulate fractions ('ribosome' and 'membrane'), is resistant to these enzymes. The 'ribosomal' peptidase activity is present partially in a latent form which becomes activated on disruption of the ribosome structure. During the transition from log phase to post-log phase growth there is a progressive increase in the specific activity of the peptidase in the 'soluble' and 'membrane' fraction and a corresponding decrease in the 'ribosome' fraction.


1981 ◽  
Author(s):  
G R Campbell ◽  
J H Chamley-Campbell

When smooth muscle from the aortic media of adult pigs, monkeys and rabbits are dispersed into single cells and seeded into primary culture they are in the contractile phenotype and do not undergo cell division when challenged with 5 or 10% whole blood serum. However, after 6-8 days the isolated cells undergo a spontaneous change in phenotype to a synthetic state whereby their contractility is lost and they become responsive to serum mitogens. This change in function is accompanied by distinct morphological changes and is reversible if the cells are seeded sufficiently dense (5 × 104 -1 × 105/ml) that a confluent monolayer of cells is achieved within 5-7 days of the original change in phenotype. If however the cells are seeded so sparsely (1 × 103 - 5 × 103/ml) that 2-3 weeks of proliferation is necessary for confluence to be achieved then the cells remain permanently in the synthetic phenotype and immediately responsive to serum mitogens upon subculture. While the cells are in the synthetic phenotype, whether proliferating or quiescent, they have a considerably decreased production of prostaglandins E2, F2α and I2. They also have a decreased ability to metabolize low density lipoprotein, a decrease in the specific activity of cholesteryl esterase and an increase in cholesterol ester deposits.The spontaneous change in phenotype from the contractile to synthetic state in culture can be prevented by seeding the contractile smooth muscle sufficiently dense (1 × 106/ ml) that a confluent monolayer is present from day 1. It can also be inhibited by a confluent monolayer of contractile smooth muscle or endothelial cells in co-culture with the sparsely-seeded smooth muscle such that the two cell layers are not in contact but bathed by the same nutrient medium. A factor which inhibits smooth muscle phenotypic change can also be extracted from pig and rabbit aortic tissue and its effect mimicked by sodium heparin at 50 units/ml.It is suggested that smooth muscle phenotype and its control are important but unrecognized factors in atherogenesis.


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