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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both iron and the major iron-binding protein ferritin are enriched in oligodendrocytes compared with astrocytes and neurons, but their functional role remains to be determined. Progressive hypoxia dramatically induces the synthesis of ferritin in both neonatal rat oligodendrocytes and a human oligodendroglioma cell line. We now report that the release of iron from either transferrin or ferritin-bound iron, after a decrease in intracellular pH, also leads to the induction of ferritin synthesis. The hypoxic induction of ferritin synthesis can be blocked either with iron chelators (deferoxamine or phenanthroline) or by preventing intracellular acidification (which is required for the release of transferrin-bound iron) with weak base treatment (ammonium chloride and amantadine). Two sources of exogenous iron (hemin and ferric ammonium citrate) were able to stimulate ferritin synthesis in both oligodendrocytes and HOG in the absence of hypoxia. This was not additive to the hypoxic stimulation, suggesting a common mechanism. We also show that ferritin induction may require intracellular free radical formation because hypoxia-mediated ferritin synthesis can be further enhanced by cotreatment with hydrogen peroxide. This in turn was blocked by the addition of exogenous catalase to the culture medium. Our data suggest that disruption of intracellular free iron homeostasis is an early event in hypoxic oligodendrocytes and that ferritin may serve as an iron sequestrator and antioxidant to protect cells from subsequent iron-catalyzed lipid peroxidation injury.
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PMID:Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes. 776 25

X-Ray analysis of the ferritin of Escherichia coli (Ec-FTN) and of Ec-FTN crystals soaked in (NH4)2Fe(SO4)2 has revealed the presence of three iron-binding sites per subunit. Two of these form a di-iron site in the centre of the subunit as has been proposed for the 'ferroxidase centres' of human ferritin H chains. This di-iron site, lying within the 4-alpha-helix bundle, resemble those of ribonucleotide reductase, methane monoxygenase and haemerythrin. The third iron is bound by ligands unique to Ec-FTN on the inner surface of the protein shell. It is speculated that this state may represent the nucleation centre of a novel type of Fe(III) cluster, recently observed in Ec-FTN.
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PMID:Direct observation of the iron binding sites in a ferritin. 807 May 75

A procedure for trapping small molecules inside the interior of horse spleen ferritin (HoSF) and methods for characterizing HoSF and its small entrapped molecules are described. HoSF is first dissociated into subunits by adjustment to pH 2 in the presence of the small molecules to be trapped. The pH of the dissociated HoSF is then increased to 7 at which time the dissociated subunits reassemble reforming the 24-mer HoSF, thereby trapping solvent within its interior. HoSF is then separated from unbound molecules by dialysis, ultrafiltration, and/or ammonium sulfate precipitation. Sephadex G-25 and DEAE chromatographic methods were also used to separate HoSF from unbound small molecules. Capillary electrophoresis (CE) was used to demonstrate the association of small molecules with HoSF after the pH-induced unfolding-refolding process. The pH indicator neutral red was clearly associated with HoSF and presumed trapped within the ferritin interior. Acid/base titrations suggested that the trapped indicator had a different pKa than the free indicator, a result which indicates that the ferritin interior is different than the external solution. The utility of using trapped molecules for gaining information on ferritin function is proposed and discussed.
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PMID:Molecular entrapment of small molecules within the interior of horse spleen ferritin. 811 6

A transferrin-independent iron transport system in cells containing transferrin receptors was described previously by several investigators. Prior studies did not identify the proteins involved in this alternate iron transport pathway. Using a human-derived erythroleukemia tissue culture line, iron-binding proteins were isolated from cytosol and cell membranes. The cytosol protein was soluble in 60% ammonium sulfate, had a molecular mass similar to mobilferrin (56 kDa), and reacted with anti-mobilferrin antibodies. The water-insoluble radiolabeled protein was solubilized with Nonidet P-40 and immunoprecipitated with monoclonal antibody against beta 3 human integrin. Pulse-chase studies suggested sequential passage of iron to integrin, mobilferrin, and ferritin, respectively. Thus, the alternate iron transport pathway contained proteins similar to those observed in intestinal cells which did not possess transferrin receptors on their absorptive surface. The alternate iron transport pathway is only partially shared with zinc and cadmium. Mobilferrin bound zinc and iron competitively, but the two metals were not transported competitively into K562 cells. Immunoprecipitates of integrin containing radiozinc were obtained with a monoclonal antibody against beta 1 human integrin. This suggested iron and zinc may utilize different integrins to passage the cell membrane.
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PMID:Alternate iron transport pathway. Mobilferrin and integrin in K562 cells. 812 27

Ferritin is a 24 subunit protein that controls biomineralization of iron in animals, bacteria, and plants. Rates of mineralization vary among members of the ferritin family, particularly between L and H type subunits of animal ferritins which are differentially expressed in various cell types. To examine ferritin from a highly differentiated cell type and to clarify the relationship between ferritin structure and function, bullfrog red cell L ferritin has been cloned, overexpressed in E. coli, and crystallized under two conditions. Crystals were obtained at high ionic strength in the presence of MnCl2 at a concentration comparable to that of the protein and in the presence of MgCl2 at a concentration much higher than that of the protein. Under both crystallization conditions, the crystals are tetragonal bipyramids in the space group F432 with unit cell dimensions a = b = c = 182 +/- 0.5 A. Crystals obtained in the presence of manganese and ammonium sulfate diffract to 1.9 A, while those obtained in the presence of magnesium and sodium tartrate diffract to 1.6 A. Isomorphous crystals have been obtained under similar conditions for a site-directed mutant with a reduced mineralization rate in which Glu-57, -58, -59, and -61 are all replaced by Ala. The structure of wild type L-subunit with magnesium has been solved by molecular replacement using the calcium salt of human liver H subunit (Lawson et al., Nature (London) 349:541-544, 1991) as the model. The crystallographic R factor for the 6-2.2 A shell is 0.21. The overall fold of human H and bullfrog L ferritins is similar with an rms difference in backbone atomic positions of 0.97 A. The largest structural differences occur in the D helix and the loop connecting the D and E helices of the four helix bundle. Because red cell L ferritin and liver H ferritin show differences in both rates of mineralization and three-dimensional structure, more detailed comparisons of these structures are likely to shed new light on the relationship between conformation and function.
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PMID:Crystallization and structural analysis of bullfrog red cell L-subunit ferritins. 815 61

Accumulation of Fe in the myocardium in circumstances of transferrin saturation is associated with heart failure in Fe-loaded patients. To characterize the underlying causes of this phenomenon, we measured the flux as well as the speciation of Fe in normal and Fe-loaded cultures of rat myocardiocytes. Fe loading with low-molecular-weight Fe (ferric ammonium citrate) promoted a dose- and time-dependent increase in the rate of uptake of non-transferrin-bound Fe (NTBI) that was positively correlated (R = 0.9, p < 0.005) with cellular iron content. At concentrations sufficient to produce this up-regulation, membrane integrity was unaffected but the rate of spontaneous beating of the cells was decreased by 60%. The enhanced rate of NTBI uptake in Fe-loaded cells reverted to control rates after treatment with therapeutic concentrations of Fe chelators deferoxamine, 1,2-dimethyl-3-hydroxypyrid-4-one and 1,2-diethyl-3-hydroxypyrid-4-one under conditions where approximately 80% of the cellular Fe was removed by chelation. Fe loading of cultured myocytes also induced shifts in Fe speciation. Thus the ratio of Fe bound in hemosiderin-like precipitates to ferritin-bound Fe increased twofold, from a range of 0.84 to 1.44 in control cells to 1.96 to 3.3 in iron-loaded cells. This increased ratio was similar to that measured in the heart and liver of a thalassemic patient who underwent a double transplant for the failure of both organs, even though the Fe content of the heart (mean, 5.8 mg Fe/gm dry weight) was much less than that of the liver (28.1 mg/gm dry weight). These results suggest that increased rates of uptake of NTBI may exacerbate iron loading of the heart and contribute to iron-mediated cardiotoxicity, whereas the clinical benefits of chelation therapy may be enhanced by the down-regulation of NTBI uptake.
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PMID:Effects of iron loading on uptake, speciation, and chelation of iron in cultured myocardial cells. 832 Apr 86

One mechanism by which Listeria monocytogenes is thought to obtain iron required for growth is through the extracellular reduction of a ferric iron source to the ferrous form. To better characterize this reductase activity we have developed a simple plate assay that allows detection of colonies of Listeria species able to reduce ferric iron. Cells are plated on an agar base medium containing a ferric iron source and ethylenediamine dihydroxyphenylacetic acid. Colonies are then overlain with soft agarose containing NADH, flavin mononucleotide, and Ferrozine, a chelator of ferrous iron. Colonies able to reduce the ferric iron source form a red-purple color as the ferrous iron is complexed with ferrozine. Using this qualitative assay we have shown that all species of Listeria are able to reduce ferric iron when presented as ferric ammonium citrate whereas most other species of Gram-positive and Gram-negative bacteria are not. Only Clostridium perfringens was able to reduce ferric iron to the same extent as Listeria. Listeria monocytogenes was further shown to be capable of reducing various ferric iron salts as well as iron bound to ferritin, transferrin, and 2,3-dihydroxybenzoic acid in the agar plate assay. The utility of this assay was demonstrated by using it to screen a bank of Tn916-derived mutants of L. monocytogenes for clones unable to reduce ferric iron. Four such mutants were identified and all were shown to have greatly decreased ferric reductase activity.
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PMID:Reduction of ferric iron by Listeria monocytogenes and other species of Listeria. 833 Feb 59

Mononuclear cells from 5 normal men and 5 patients homozygous for hereditary haemochromatosis (HFE) have been incubated for 18 h with or without the addition of sheep red blood cells coated with antibody (SRBC). In the absence of SRBC mean H type ferritin concentrations were greater than L type (normals: mean L type 11.6 ng/10(6) cells, H type 15.5; patients, L type 23.5 ng/10(6) cells, H type 41.6). In the presence of SRBC, monocyte L type ferritin concentrations increased considerably (76 ng/10(6) cells in normals and 141 ng/10(6) cells in patients) but H type ferritin concentrations were the same or decreased compared with incubation in medium only. Incubation with additional iron (ferric ammonium citrate, 2.5 micrograms Fe/ml) increased both H and L type ferritin concentrations. Erythrophagocytosis thus appears to cause differential regulation of H and L ferritin subunit synthesis or breakdown. Normal subjects and patients do not differ in this response to erythrophagocytosis.
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PMID:Red cell destruction by human monocytes--changes in intracellular ferritin concentration and phenotype. 843 11

The effect of horse spleen ferritin (HFR) on the production of superoxide anion (O2.-) by equine blood monocytes was investigated. Preincubation of monocytes with HFR resulted in pronounced inhibition of O2.- production in response to phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and opsonized zymosan (OZ). The inhibitory effect of HFR upon stimulation of monocytes with PMA was both dose and time dependent. Maximum inhibition (90%) was observed after preincubation of monocytes with HFR (2 mg/ml) for 18 h before stimulation with PMA. ApoHFR at the same concentration showed only about one-third of the inhibitory effect of iron-saturated HFR. Various iron complexes, such as iron dextran, hemin, or ferric ammonium sulfate, had no significant effect on O2.- production by monocytes. Neither catalase (Cat) nor desferrioxamine (DFO) changed the inhibitory effect of HFR. These findings suggest that HFR may play an important role in inhibition of superoxide generation by equine monocytes. Although the mechanism of this inhibition remains unknown, the results obtained suggest that it is not due to ferritin-dependent oxidative inactivation of the NADPH-oxidase system in stimulated monocytes.
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PMID:Horse spleen ferritin inhibits superoxide production by equine blood monocytes in vitro. 872 16

Vibrio parahaemolyticus is an important enteropathogen in Japan, Taiwan and other coastal regions. The influence of the regulation of iron on the pathogenesis of this pathogen has not been well characterized. The growth of pathogenic and non-pathogenic strains of V. parahaemolyticus on iron-limited agar plates was stimulated by ferritin, lactoferrin and transferrin at 30 microM, and also by hemin, hemoglobin and ferric ammonium citrate at 100 microM. Spontaneous iron-utilizing mutant strains (mutants) were derived from a clinical strain, ST550. Compared with the parent strain, lowered virulence was demonstrated for these mutants, as assayed by adult mouse and suckling mouse models. The in vivo growth and enterotoxigenicity of these mutants were also lower in the suckling mice. Adherence of the mutants to excised mouse intestine was lower as demonstrated by scanning electron microscopy. The iron-regulated outer membrane protein profile also changed in selected mutants. These results indicate that iron-regulated outer membrane proteins and other unknown factors associated with iron utilization may have profound influences, besides iron acquisition, on the pathogenesis of V. parahaemolyticus.
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PMID:Utilization of iron sources and its possible roles in the pathogenesis of Vibrio parahaemolyticus. 898 34


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