Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study (Minotti, G., and Ikeda-Saito, M. (1991) J. Biol. Chem. 266, 20011-20017) we demonstrated the existence of a M(r) 66,000 microsomal iron protein (MIP) which stimulates NADPH oxidation by shunting electrons from NADPH-cytochrome P-450 reducase to its bound Fe(III). In the present study, purified MIP was depleted of iron and the apoMIP was examined for its ability to incorporate Fe(III) upon an incubation with Fe(II). It was found that apoMIP had an oxygen-dependent ferroxidase activity coupled with the incorporation of Fe(III). The reconstituted MIP exhibited a Fe(III) content and an NADPH oxidation activity similar to those of native MIP. However, the reconstitution of MIP from apoMIP and Fe(II) had to be performed in the presence of detergents to prevent the formation of protein aggregates and the oxidative incorporation of an iron which could not react with NADPH-cytochrome P-450 reductase. This redox inactive iron was probably bound nonspecifically to artifactual sites formed by the protein aggregates.
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PMID:Fe(II) oxidation and Fe(III) incorporation by the M(r) 66,000 microsomal iron protein that stimulates NADPH oxidation. 155 97

In unseparated human blood the reactivity of yeast copper (I)-thionein on TPA-activated polymorphonuclear leukocytes was evaluated and compared with low Mr copper chelates exerting Cu2Zn2 superoxide dismutase mimetic activity. Cu, 18 microM, in the form of Cu-thionein was sufficient to inhibit the superoxide production of activated human blood phagocytes by 50%. Furthermore, the scavenging of hydroxyl radicals and singlet oxygen by Cu(I)-thionein was determined, using the 2-deoxyribose fragmentation assay induced by decaying K3CrO8 and the NADPH oxidation caused by UVA illuminated psoralen, respectively. The inhibitory reactivity of Cu-thionein in both assays was compared with that of serum proteins including albumin, ceruloplasmin, transferrin, and ferritin. The galactosamine/endotoxin-induced hepatitis in male NMRI mice was used to evaluate the antiinflammatory reactivity of Cu-thionein in vivo. The serum copper, superoxide dismutase, and sorbitol dehydrogenase concentrations, as well as the activity of polymorphonuclear leukocytes in unseparated blood seemed most appropriate to quantify the protective capacity of Cu-thionein in the course of an oxidative stress-dependent liver injury. The intraperitoneal application of 32.5 mumols/kg thionein-Cu limited this damage to 45%.
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PMID:Antiinflammatory reactivity of copper(I)-thionein. 224 84

The addition of ceruloplasmin to bovine cardiac sarcolemmal vesicles supplemented with NADPH was able to reduce the formation of adrenochrome from adrenaline. This inhibitory effect appears at 2.5 microM ceruloplasmin and it is almost complete at the level of 20 microM.
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PMID:Inhibition by ceruloplasmin of the cardiac sarcolemmal adrenochrome formation. 299 71

Content of lipid peroxidation products in liver mitochondria, enzymatic system of the peroxidation initiation (NADPH.H+- and NADH.H+-dependent oxydoreductases) at the early and final steps of liver microsomal redoxchain as well as the activity of protective enzymes superoxide dismutase, ceruloplasmin, catalase and glutathione reductase, preventing the excessive accumulation of lipid peroxidation products in liver mitochondria and erythrocytes were studied in rats with hypokinesia within 1 and 2 months. An increase in content of diene conjugates and malonic dialdehyde as well as in activity of NADPH.H+- and NADH.H+-nitroblue tetrazolium-oxydoreductases in liver microsomes, a decrease in activity of catalase and superoxide dismutase in liver mitochondria were observed in the animals within two months of their mobility restriction. These alterations were among the essential mechanisms responsible for an increase in content of lipid peroxidation products under conditions of hypokinesia.
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PMID:[Enzyme system of initiation and protection against lipid peroxidation in the liver and blood of rats with hypokinesia]. 336 22

Microsomal lipid peroxidation induced by NADPH, but not by ascorbate, was found to be inhibited by liver cytosol. This inhibition was not dependent on glutathione and was enhanced by ADP in presence of Fe2+ at a concentration of 50 microM or higher. ATP was also effective, but not AMP or cyclic AMP. The cytosolic factor appeared to be a protein as it was heat-labile (greater than 70 degrees C), was non-dialyzable and was precipitated by ammonium sulfate and acetone. It was stable for several months in frozen state and also when heated at 50 degrees C for 10 min. The inhibition by the cytosolic protein was obtained by producing a lag in the activity of lipid peroxidation and was reversed by ceruloplasmin but not by catalase, cytochrome c, hemoglobin or superoxide dismutase. This inhibitory effect by cytosol was limited to formation of lipid peroxides whereas oxygen uptake and NADPH oxidation remained unaffected. Regulation of lipid peroxidation by nucleotide-Fe complexes and cytosolic proteins is indicated by these studies.
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PMID:Inhibition of microsomal lipid peroxidation by cytosolic protein in presence of ADP and high concentration of Fe2+. 650 75

The concentration of lipoperoxides (estimated as thiobarbituric acid-reactive material) and some components of the antioxidant defence system have been compared in various tissues of lean and congenitally obese mice. NADPH-stimulated lipoperoxide generation in vitro was significantly higher in microsomes (microsomal fractions) prepared from obese hepatic tissue than lean. Plasma, liver and brain lipoperoxide concentration was significantly higher in obese mice. In blood derived from obese mice the concentration of non-enzymic antioxidants including caeruloplasmin and vitamin A was higher, but hepatic retinol concentration was lower in these animals. In all the tissues assayed the glutathione peroxidase activity against H2O2 was less than its activity against cumene hydroperoxide. Assayed with either substrate, glutathione peroxidase activity was significantly higher in the brain and blood of obese mice than their lean counterparts. Conversely, liver glutathione peroxidase was decreased in obese animals, representing 43% of the activity of the lean-mouse liver enzyme against H2O2 and 81% of the cumene hydroperoxide-reducing activity. The liver of obese mice had significantly less, and the kidneys more, oxidized glutathione than the corresponding tissues of lean mice. Further investigations on hepatic tissue indicated that glutathione reductase activity was lower in the obese animals, but there was no significant difference between glucose-6-phosphate dehydrogenase activity in obese and lean mice.
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PMID:Abnormal antioxidant defence in some tissues of congenitally obese mice. 672 63

Microsomal NADPH-dependent lipid peroxidation catalyzed by ADP-Fe3+ was inhibited by the addition of caeruloplasmin. The antioxidant effect of caeruloplasmin was independent of the superoxide anion (O-2) scavenging activity. Since caeruloplasmin enhanced the function of ADP-Fe3+ acting as electron acceptor for microsomal electron transport system, the antioxidant effect of caeruloplasmin is considered to depend on the ferroxidase activity.
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PMID:Antioxidant effect of caeruloplasmin on microsomal lipid peroxidation. 682 43

Almost all iron uptake by fungi involves reduction from Fe(III) to Fe(II) in order to facilitate ligand exchange. This leads to two mechanisms: uptake before reduction, or reduction before uptake. Many fungi secrete specific hydroxamate siderophores when short of iron. The mechanism with uptake before reduction is described in the context of siderophore synthesis and usage, since it applies to many (but not all) siderophores. The hydroxamate functional group is synthesized from ornithine by N5 hydroxylation and acylation. In most fungal siderophores, two or three modified ornithines are joined together by a non-ribosomal peptide synthetase. The transcription of these genes is regulated by an iron activated repressor. There is evidence that the iron-free siderophore may be stored in intracellular vesicles until secretion is required. After loading with iron, re-entry is likely to be via a proton symport. In some fungi, siderophores are used for iron storage. The iron is liberated by an NADPH-linked reductase. The second mechanism starts with Fe(III) reduction. In yeast, this is catalysed by an NADPH-linked transmembrane reductase, which has homology with the NADPH oxidase of neutrophils. There are two closely similar reductases with overlapping roles in Fe(III) and Cu(II) reduction, while the substrates for reduction include Fe(III)-siderophores. External reductants, which may be important in certain fungi, include 3-hydroxyanthranilic acid, melanin, cellobiose dehydrogenase and 2,5-dimethylhydroquinone. In yeast, a high-affinity iron uptake pathway involves reoxidation of Fe(II) to Fe(III), probably to confer specificity for iron. This is catalysed by a copper protein which has homology with ceruloplasmin, and is closely coupled to Fe(III) transport. The transcription of these genes is regulated by an iron-inhibited activator. Because of its copper requirement, the high-affinity pathway is blocked by disruption of genes for copper metabolism. A low-affinity uptake transports Fe(II) directly and is important in anoxic growth. In many fungi, mechanisms with internal or external reduction are both important. The external reduction is applicable to almost any Fe(III) complex, while internal reduction is more efficient at low iron but requires a siderophore permease through which toxins might enter. Both mechanisms require close coupling of Fe(III) reduction and Fe(II) utilization in order to minimize production of active oxygen.
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PMID:Iron uptake by fungi: contrasted mechanisms with internal or external reduction. 1090 54

Hypoxia-inducible factor (HIF)-1 activation in response to hypoxia requires mitochondrial generation of reactive oxygen species (ROS). In contrast, the requirement of ROS for HIF-1 activation by growth factors like insulin remains unexplored. To explore that, insulin-sensitive hepatic cell HepG2 or cardiac muscle cell H9c2 cells were pretreated with NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) or apocynin and HIF-1 activation was tested by electrophoretic mobility shift and reporter gene assay. Antioxidants DPI or apocynin completely blocked insulin-stimulated HIF-1 activation. The restoration of HIF-1 activation by H(2)O(2) in DPI-pretreated cells not only confirmed the role of ROS but also identified H(2)O(2) as the responsible ROS. The role of NADPH oxidase was further confirmed by greater stimulation of HIF-1 during simultaneous treatment of suboptimal concentration of insulin along with NADPH but not by NADH. The role of oxidant generated by insulin is found to inhibit the protein tyrosine phosphatase as suggested by the following observations. First, tyrosine phosphatase-specific inhibitor sodium vanadate compensates DPI-inhibited HIF-1 activity. Second, sodium vanadate stimulates HIF-1 activation with suboptimal concentration of insulin. Third, DPI and pyrrolidene dithiocarbamate (PDTC) blocks insulin-receptor tyrosine kinase activation. The activity of phosphatidylinositol 3-kinase as evidenced by Akt phosphorylation, involved in HIF-1 activation, is also dependent on ROS generation by insulin. Finally, DPI pretreatment blocked insulin-stimulated expression of genes like VEGF, GLUT1, and ceruloplasmin. Overall, our data provide strong evidence for the essential role of NADPH oxidase-generated ROS in insulin-stimulated activation of HIF-1.
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PMID:Insulin-induced activation of hypoxia-inducible factor-1 requires generation of reactive oxygen species by NADPH oxidase. 1708 41