Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione is activated to a mutagen by gamma-glutamyl transpeptidase. Other thiols, such as cysteine, penicillamine, cysteine ethylester, and cysteinylglycine, are direct mutagens in the Ames Salmonella mutagenicity test. Thiol mutagenesis is oxidative in nature and involves H2O2 and possibly hydroxyl radicals. Transition metals are crucial for thiol autoxidation. The role of copper and ceruloplasmin (CP) in thiol-dependent mutagenesis was studied in Salmonella typhimurium strain TA102. Cu and CP at low concentrations enhanced thiol-dependent mutagenesis in the presence, but not in the absence, of added Fe. The degree of enhancement depended on the type of thiol. At high Cu or CP concentrations, thiol mutagenesis was inhibited. Cu also decreased the mutagenicity of H2O2. Cu- and CP-enhanced mutagenesis were inhibited by radical scavengers, catalase, and peroxidase but not by superoxide dismutase. The effects of Cu and CP on thiol-dependent mutagenesis were similar to their effects on thiol-driven lipid peroxidation. The results indicate that the role of Cu and CP in the enhancement of thiol mutagenesis is the facilitation of the transfer of electrons from a thiol to iron, rather than in catalysis of the Fenton reaction.
Environ Mol Mutagen 1997
PMID:Role of copper and ceruloplasmin in oxidative mutagenesis induced by the glutathione-gamma-glutamyl transpeptidase system and by other thiols. 902 Mar 9

Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system containing glutathione (GSH), purified gamma-glutamyl transpeptidase (GGT), and EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration, GGT activity, the presence of iron, and the chelation of copper by o-phenanthroline. High concentrations of CP inhibited LPO. Cu- and CP-enhanced, GSH-GGT-driven LPO was inhibited by the chain-breaking radical scavengers butylated hydroxyanisol, alpha-tocopherol, and Trolox C (a synthetic analog of alpha-tocopherol) but not by the hydroxyl scavenger mannitol. Ascorbic acid increased LPO in the presence of Cu or CP. Cu-enhanced LPO was partially sensitive to superoxide dismutase but not to catalase or horseradish peroxidase. The results indicate that Cu and CP enhance thiol-driven LPO and promote thiol-dependent mutagenesis by a very similar, if not the same, mechanism and are in agreement with the idea that this enhancement is due to redox reactions of chelated Cu and Fe, rather than to the reactivity of Cu in the Fenton reaction.
Environ Mol Mutagen 1997
PMID:Promotion of glutathione-gamma-glutamyl transpeptidase-dependent lipid peroxidation by copper and ceruloplasmin: the requirement for iron and the effects of antioxidants and antioxidant enzymes. 902 Mar 10

Mammalian ferritins are 24-mers assembled from two types of polypeptide chain which provide the molecule with different functions. H(eavy) chains catalyse the first step in iron storage, the oxidation of iron(II). L(ight) chains promote the nucleation of the mineral ferrihydrite enabling storage of iron(III) inside the protein shell. We report here the comparison of the three-dimensional structures of recombinant human H chain (HuHF) and horse L chain (HoLF) ferritin homopolymers, which have been refined at 1.9 A resolution. There is 53% sequence identity between these molecules, and the two structures are very similar, the H and L subunit alpha-carbons superposing to within 0.5 A rms deviation with 41 water molecules in common. Nevertheless, there are significant important differences which can be related to differences in function. In particular, the centres of the four-helix bundles contain distinctive groups of hydrophilic residues which have been associated with ferroxidase activity in H chains and enhanced stability in L chains. L chains contain a group of glutamates associated with mineralisation within the iron storage cavity of the protein.
J Mol Biol 1997 May 02
PMID:Comparison of the three-dimensional structures of recombinant human H and horse L ferritins at high resolution. 915 81

The amino acid and carbohydrate analysis of scyllin, a low molecular weight lectin purified from Scylla serrata (edible crab) haemolymph reveal that scyllin is rich in acidic and neutral amino acids and contains high amount of mannose. UV absorption of scyllin is perturbed by DMSO at 272 nm showing the presence of tryptophan molecule in scyllin exposed and accessible to the solvent. The oxidation of tryptophan molecule by N-bromosuccinimide results in loss of haemagglutinating activity of lectin. The study of thermodynamic parameters of scyllin-glycoproteins interaction suggests that ceruloplasmin is the most potent inhibitors of scyllin of all the glycoproteins studied.
Biochem Mol Biol Int 1997 Jun
PMID:Further biochemical and biophysical characterisation of scyllin, Scylla serrata hemolymph lectin. 919 99

The possible relation of the increase in the concentration of copper (Cu) in the bloodstream with the increased supply of Cu to ceruloplasmin in the liver was examined in relation to the onset of jaundice in Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease. The Cu concentration in serum and that in liver, and then that in kidneys of LEC rats were correlated, and then the relationship between the Cu concentration in serum and the malondialdehyde (MDA) concentration in the liver, a marker for lipid peroxidation, and also the activities of alanine aminotransferase and lactate dehydrogenase, marker enzymes for liver damage, were examined. An increase in the Cu concentration in liver induced significant increases in the Cu concentrations in serum and kidneys, and their relationship was different before and after the onset of jaundice, as reflected by the concentration of Cu in serum (lower than 1.5 and higher than 2.7 micrograms/ml, respectively). The relationship between the MDA concentration in liver and the Cu concentration in serum showed a characteristic change between before and after the onset of jaundice. The marker enzymes for liver damage increased significantly with age, and showed distinct responses at the Cu concentration of 1.5-2.7 micrograms/ml in serum. The results suggest that the Cu concentration in plasma reflects the on-going biological and toxicological actions of non-MT-bound Cu in the livers of LEC rats.
Res Commun Mol Pathol Pharmacol 1997 Dec
PMID:Copper in plasma reflects its status and subsequent toxicity in the liver of LEC rats. 948 27

The concentrations of ceruloplasmin could not be determined by comparing the oxidase activities toward p-phenylenediamine and o-dianisidine in rat whole serum with those of purified ceruloplasmin because of the different specific amine oxidase activities of ceruloplasmin purified from normal and gamma-irradiated rats and the lability caused by freezing and thawing. A competitive enzyme linked immunosorbent assay with antigens immobilized on the solid phase was developed to measure the ceruloplasmin in rat serum. The blocking materials and pH of the coating buffer had an effect on the amount of ceruloplasmin bound to the microtiter plates. The blocking materials nonspecifically reacted with the rabbit anti-rat ceruloplasmin IgG, and consequently the coating sensitivity was decreased and standard curves were not formed completely. Because rabbit anti-rat ceruloplasmin IgG did not show any cross reactivity with rat albumin and hemoglobin, these proteins did not affect the assay at a concentration of 200 micrograms/ml. This assay is useful for measuring the concentration of ceruloplasmin in normal and irradiated rat serum.
Biochem Mol Biol Int 1998 Jul
PMID:Development of a competitive enzyme linked immuno sorbent assay to measure ceruloplasmin in gamma-irradiated rat serum. 967 61

Particulate air pollution causes increased cardiopulmonary morbidity and mortality, but the chemical determinants responsible for its biologic effects are not understood. We studied the effect of total suspended particulates collected in Provo, Utah, an area where an increase in respiratory symptoms in relation to levels of particulate pollution has been well documented. Provo particulates caused cytokine-induced neutrophil chemoattractant-dependent inflammation of rat lungs. Provo particulates stimulated interleukin-6 (IL-6) and IL-8 production, increased IL-8 messenger RNA (mRNA) and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured BEAS-2B cells, and stimulated IL-8 secretion in primary cultures of human bronchial epithelium. Cytokine secretion was preceded by activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and was reduced by treatment of cultures with superoxide dismutase, deferoxamine, or N-acetylcysteine. These biologic effects were replicated by culturing BEAS cells with quantities of Cu2+ found in Provo extract. IL-8 secretion by BEAS cells could be modified by addition of normal constituents of airway lining fluid to the culture medium. Mucin significantly reduced IL-8 secretion, and ceruloplasmin significantly increased IL-8 secretion and activation of NF-kappaB. These findings suggest that copper ions may cause some of the biologic effects of inhaled particulate air pollution in the Provo region of the United States, and may provide an explanation for the sensitivity of asthmatic individuals to Provo particulates that has been observed in epidemiologic studies.
Am J Respir Cell Mol Biol 1998 Sep
PMID:Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution. 973 Aug 64

The potential absorptive role of the yolk sac membrane was evaluated by examining protein and enzyme patterns in embryonic fluids and by comparing the synthetic capacity of the secondary yolk sac, fetal liver and placenta for human chorionic gonadotrophin (HCG) and alpha-fetoprotein (alphaFP). In yolk sac fluid samples, protein electrophoresis showed two main electrophoretic bands with mobilities comparable to those of albumin and interalbumin-alpha1-globulin, and immunoblotting revealed the presence of albumin, alphaFP, alpha1-antitrypsin, alpha2-macroglobulin, transferrin, complement factors 3 and 4 and immunoglobulin G. In coelomic fluid, similar results were obtained, except for the absence of alpha2-macroglobulin and the presence of ceruloplasmin and IgA. After electrophoresis and immunoblotting with specific antibodies, beta-HCG was detected in all placental homogenates and culture media but was not revealed in any of the corresponding yolk sac tissue samples. Reverse transcription-polymerase chain reaction (RT-PCR) showed that all placental samples express beta-HCG mRNA whereas all yolk sac and liver samples express alphaFP mRNA. These findings suggest that the yolk sac membrane is an important zone of transfer between the extra-embryonic and embryonic compartments and may also help to further develop therapeutic protocols making use of fetal somatic gene therapy by injecting transduced cells into the exocoelomic cavity.
Mol Hum Reprod 1998 Sep
PMID:Protein and enzyme patterns in the fluid cavities of the first trimester gestational sac: relevance to the absorptive role of secondary yolk sac. 978 45

The chain-breaking antioxidant potential of caeruloplasmin and bovine serum albumin (BSA) has been investigated in comparison with other well-established antioxidants. Their Oxygen Radical Absorbing Capacity (ORAC), was measured by using beta-phycocyanin (beta-PC) as a fluorescent indicator protein, 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) as a peroxyl radical generator and the water soluble vitamin E analogue, Trolox, as a reference standard. The relative peroxyl absorbing capacities/mole for Trolox, caeruloplasmin, heat-denatured caeruloplasmin (hCP), catalase, bovine serum albumin (BSA), superoxide dismutase (SOD), and deferoxamine were 1; 2.6; 3.3; 3.7; 1.2; 0.1; 0.2, respectively. Caeruloplasmin was far more effective as a peroxyl radical scavenger than SOD, deferoxamine and BSA, but slightly less effective than catalase. The peroxyl radical absorbing capacity of caeruloplasmin was enhanced by heat-denaturation of the protein. Electron paramagnetic resonance (EPR) spectroscopy using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin-trap, was applied in order to measure the scavenger abilities of caeruloplasmin on superoxide radical and hydroxyl radical production and the concentration required to inhibit by 50% oxygen free radical formation (IC50) was determined. The IC50 values of caeruloplasmin, hCP, and BSA for the superoxide radical were 12, 2, 260 microM and for the hydroxyl radical 15, 2, 200 microM. These results show that caeruloplasmin is an effective chain-breaking antioxidant for a variety of radicals, independently of its catalytic ferroxidase activity.
Mol Cell Biochem 1998 Dec
PMID:Direct evidence of caeruloplasmin antioxidant properties. 987 63

Ceruloplasmin is excreted mostly in the apo-form in Wilson's disease patients and Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model for Wilson's disease, and hence the concentration of Cu in the plasma is low. However, it increases toward and at the onset of acute hepatitis in LEC rats, the increased Cu in the plasma being bound to ceruloplasmin, metallothionein and albumin. Changes in the concentration of Cu in red blood cells (RBCs) were monitored with age for the first time together with that in the plasma in LEC rats. Cu in the RBCs was found to increase to a 5-7 times higher level than that in the plasma toward the onset and peaked at the onset, the pattern being similar to that in the plasma. The source of the Cu increase in the RBCs was discussed, and it was assumed that the so-called free Cu ions that leak from the damaged hepatocytes are bound to albumin and/or taken up by the RBCs.
Res Commun Mol Pathol Pharmacol 1999 Feb
PMID:Copper increases in both plasma and red blood cells at the onset of acute hepatitis in LEC rats. 1046 85


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