Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities.
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PMID:Investigation of the anti-inflammatory properties of hydroxypyridinones. 225 52

Eleven patients on haemodialysis were treated with erythropoietin (EPO), 50-200 U kg-1 once to three times a week, for up to 1 year. After outset of EPO all patients became transfusion-independent. Four patients did not reach the target haemoglobin (Hb) level 100 g l-1 in 5 months. These patients had higher serum concentrations of aluminium (225 +/- 87 micrograms l-1, mean +/- SD) than the responding patients (55 +/- 56 micrograms l-1). Addition of desferrioxamine to treatment with EPO resulted in a rapid rise in Hb values in these patients. Thus, aluminium may inhibit EPO responsiveness. All patients were iron overloaded. Serum ferritin levels declined in all but one patient with secondary haemochromatosis. In exercise tests the aerobic capacity and oxygen uptake increased during EPO therapy. Peak oxygen consumption (Vo2 peak), oxygen pulse, oxygen uptake at anaerobic threshold (AT) and total work output (W max) increased 19%, 36%, 26% and 24%, respectively. Lean body mass (LBM) increased by 8%. Taken together, all clinical EPO effects measured appeared clinically favourable.
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PMID:Beneficial effects of erythropoietin on haematological parameters, aerobic capacity, and body fluid composition in patients on haemodialysis. 280 6

Convincing evidence is presented that oxygen free radicals are involved in the pathogenesis of rheumatoid arthritis (RA). Superoxide is produced by polymorphonuclear leucocytes (PMN) in synovial fluid and by macrophages in the synovial membrane. Tissue damage typical for free radical attack is detected in RA. No absolute deficiency of protective factors is found in RA compared to controls, but the available protection is insufficient to cope with all radicals formed. The toxicity of superoxide is increased by iron. It is doubtful whether a low molecular weight iron pool is present. Superoxide is able to release iron from ferritin, providing a suitable source of iron, for the formation of hydroxyl radicals. This new pathogenetic mechanism stimulates to the application of iron chelators in the treatment of RA. Preliminary results with desferrioxamine were disappointing because of serious side-effects. Hopefully in the future intra-articular injection of iron chelators with better pharmacodynamics will be possible. The interaction of free radicals and ferritin is probably also involved in the pathogenesis of other inflammatory diseases such as systemic lupus erythematosus, hepatitis, and haemochromatosus.
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PMID:Superoxide dependent iron release from ferritin in inflammatory diseases. 283 31

Oxidative deposition of iron in ferritin or the autoxidation of iron in the absence of protein produces radicals from Good's buffers. Radical species are formed from the piperazine ring-based buffers Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), Epps 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid, and Pipes 1,4-piperazinediethanesulfonic acid, but not from Mes (4-morpholineethanesulfonic acid) which contains a morpholine ring. The radicals all have half-lives around 10 min and display very similar electron paramagnetic resonance spectra consisting of at least 30 lines. The Hepes radical can be formed by the addition of potassium superoxide directly to the buffer and its production during iron(II) autoxidation is inhibited by superoxide dismutase (EC 1.15.1.1). Catalase (EC 1.11.1.6) accelerates the decay of the EPR spectrum. Thus the buffer radicals are secondary radical species produced from oxygen radicals formed during the iron catalyzed Haber-Weiss process. The deoxyribose/thiobarbituric acid assay for hydroxyl radical production shows that Hepes is an effective hydroxyl radical scavenging agent. The Hepes radical can also be formed electrolytically at a potential of +0.8 V (vs standard hydrogen electrode). Oxidation of Hepes at pH 10 during the autoxidation of iron(II) or by the addition of hydrogen peroxide produces a nitroxide radical. These results indicate that piperazine ring Good buffers should be avoided in studies of redox processes in biochemistry.
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PMID:Radicals from "Good's" buffers. 284 86

Among forty adults with cyanotic congenital heart disease there was a subset of eleven patients with especially pronounced erythrocytosis, repeatedly rising haematocrit, recurring symptoms of hyperviscosity, and little or no shift of the haemoglobin/oxygen-dissociation curve. These patients were iron deficient as a result of many therapeutic phlebotomies; nevertheless their red-cell mass was comparable to that in iron-replete patients with similar, but stable, haematocrits. Iron repletion in the deficient patients resulted in rapidly increasing haematocrit and hyperviscosity. In one extreme case, erythropoiesis remained persistently iron deficient despite normal serum iron and ferritin levels. "Decompensated erythrocytosis" is an apt term for the excessive erythrocytic response and the associated phenomena.
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PMID:Chronic hypoxaemia and decompensated erythrocytosis in cyanotic congenital heart disease. 287 30

Microsomes incubated with NADPH and the cardiotoxic anticancer drug adriamycin reductively release their bound nonheme iron, which is accounted for by ferritin and an as yet uncharacterized nonferritin pool. The reaction is mediated by one-electron reduction of adriamycin to semiquinone radical and subsequent reoxidation of this radical at the expense of membrane iron to regenerate adriamycin and promote Fe2+ release. The semiquinone radical of adriamycin can also reoxidize at the expense of molecular oxygen to form superoxide. However, superoxide dismutase does not inhibit Fe2+ release, indicating either that superoxide is not involved in iron reduction or that superoxide reacts at sites which are sterically inaccessible to the enzyme. It is proposed that the reductive mobilization of membrane-bound iron may mediate the therapeutic or toxic effects of adriamycin, irrespective of the superoxide dismutase content of the target cells.
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PMID:Adriamycin-dependent release of iron from microsomal membranes. 291 83

Ischemia was simulated in rat liver perfused by physiological solution. The concentration of free iron and lipid peroxidation (LPO) products was measured 1, 2, 3, 4 and 5 hours after ischemia onset. The ESR method was used to measure free iron concentration. The LPO intensity was evaluated by the TBA test and by optical density at 232 nm. The content of free iron in cytoplasm increased in the course of ischemia with an increase in the concentration of LPO products. The content of free iron in the membranes remained unchanged. It is supposed that activation of LPO in ischemia may be caused by the appearance in the cytoplasm of a large amount of free iron. This iron can be liberated from ferritin in conditions of low oxygen concentration.
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PMID:[Role of endogenous free iron in activating lipid peroxidation in ischemia]. 298 78

In the process of lipid peroxidation of microsomes induced either by oxygen radicals generated by xanthine oxidase or by NADPH, ferritin is able to donate the necessary iron. The amount of ferritin necessary to catalyze the process of lipid peroxidation is in the physiological range. In contrast to the finding with phospholipid liposomes, catalase hardly stimulates the lipid peroxidation of microsomes.
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PMID:Ferritin, a physiological iron donor for microsomal lipid peroxidation. 300 17

Metal binding to the iron storage protein apoferritin is the first step in the process by which iron accumulates within the protein shell. In the present study, the stoichiometry of metal binding to apoferritin in solution has been examined using the probe ions Mn(II), VO(IV), and Cd(II) in conjunction with EPR spectroscopic and cadmium ion selective electrode measurements. Binding studies were carried out with the individual ions, in competition with one another, and in competition with Fe(II), Fe(III), and Tb(III). All three probe ions show binding stoichiometries near 0.3 and 0.7 metal ion per subunit, close to the theoretically predicted values of 0.33 and 0.67 for the binding of one and two metal ions, respectively, per three subunits. These results in conjunction with other data are consistent with the binding of one, and possibly two, metal ions within each of the eight hydrophilic channels which are located on 3-fold axes leading to the interior of the protein. Pairs of cadmium binding sites have been located in these channels by x-ray crystallography (Rice, D. W., Ford, G. C., White, J. L., Smith, J. M. A., and Harrison, P. M. (1983) Adv. Inorg. Biochem. 5, 39-49). The possibility that some metal binding occurs elsewhere on the protein is not precluded by the present data, however. In competition experiments between various metal ions, approximately 0.3 metal ion per subunit is readily displaced implying common binding sites in the channels for all of them. The stoichiometry of Mn(II) displacement by Fe(II) is less clear. Oxidation of Fe(II) to Fe(III) by molecular oxygen in the presence of Mn(II) regenerates some Mn(II) binding on the protein, suggesting migration of iron(III) to other protein sites, or perhaps to core.
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PMID:Metal ion complexes of apoferritin. Evidence for initial binding in the hydrophilic channels. 300 69

Partially-reduced forms of dioxygen or "oxy-radicals" (superoxide, O2-/HO2; hydrogen peroxide, H2O2; hydroxyl radical X OH) and oxidants of comparable reactivity are implicated in an increasing number of physiological, toxicological, and pathological states. Transition metal catalysis is recognized as being integral to the generation and the reactions of these activated oxygen species. Factors such as pH and chelation govern the reactivity of the transition metals with dioxygen and "oxy-radicals" and therefore influence the apparent mechanisms by which oxidative damage to phospholipids, DNA, and other biomolecules is initiated. In biological systems the concentrations of redox-active transition metals capable of catalyzing these reactions appears to be relatively low. However, under certain conditions metal storage and transport proteins (ferritin, transferrin, ceruloplasmin, etc.) may furnish additional redox active metals.
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PMID:Role of metals in oxygen radical reactions. 301 69


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