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)

We assessed the iron load content in 36 beta-thalassemia patients by NMR correlating the results with serum ferritin levels. 22 of them were affected by beta-thalassemia major on hyper-transfusional regimen (Group A), 4 by beta-thalassemia intermedia (Group B) and 10 by beta-thalassemia major, who had been previously bone marrow transplanted (Group C). In A and C Groups the liver showed the lowest signal intensity on spin echo images (p less than 0.01; p less than 0.06, respectively). A significant correlation between the summation of signals obtained from all the examined organs and serum ferritin levels was observed by evaluating both all the patients globally (r = 0.78; p less than 0.001) and the A and C Group patients. This correlation was confirmed only in the liver both in all the patients (r = 0.77; p less than 0.001) and in A and C Group patients, when the signals obtained from each organ were evaluated.
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PMID:[Nuclear magnetic resonance and iron overload in thalassemia]. 179 2

Thiourea and superoxide dismutase were effective antidotes to paraquat toxicity in an HL60 cell culture system, whereas other hydroxyl scavengers were ineffective. The efficacy of thioureas was not due to blockage of intracellular paraquat uptake, inhibition of NADPH-P-450 reductase, or reaction with the paraquat radical. Thiourea also competitively inhibited the reduction of cytochrome c by the xanthine/xanthine oxidase superoxide-generating system, and the release of iron from ferritin by superoxide radicals. The reaction of superoxide with thiourea produced a sulfhydryl compound distinct from products formed by hydrogen peroxide or hydroxyl radicals. Spectrophotometric and chromatographic studies indicated the carbon-sulfide double bond was converted to a sulfhydryl group which reacted with Ellman's reagent. Additional confirmatory evidence for the sulfhydryl compound was obtained with carbon-13 NMR and mass spectroscopies. Thus, thioureas are direct scavengers of superoxide radicals as well as hydroxyl radicals and hydrogen peroxide. The rate constant for the reduction of thiourea by superoxide was estimated at 1.1 x 10(3) M-1 s-1. The implication of this finding on free radical studies, the mechanism of paraquat toxicity, and the metabolism of thioureas is discussed.
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PMID:Thioureas react with superoxide radicals to yield a sulfhydryl compound. Explanation for protective effect against paraquat. 215 25

The knowledge of the route through which iron can enter and leave the apoferritin shell is a prerequisite for the understanding of ferritin's function. The involvement of the hydrophilic 3-fold channels in the iron uptake process has been studied by taking advantage of the reactivity of specific residues that line such channels, i.e., glutamic acid-127 and aspartic acid-130, the major Cd(II) binding sites, and cysteine-126. 113Cd NMR experiments have provided direct evidence for the competition between Fe(II) and Cd(II) binding to major Cd(II) binding sites on the protein and or a higher affinity of Fe(II) for these sites, in line with the well-known inhibitory effect of Cd(II) on iron uptake. Further evidence for the use of the 3-fold channels in the iron entry process has been obtained by means of chemical modification of Cys-126 with different mercurials. In particular, the introduction of the additional carboxylate carried by p-(chloromercuri)benzoate near Asp-127 and Glu-130 increases the initial rate of iron uptake and affects the coordination geometry of the metal in the Fe(III)-apoferritin complex as indicated by optical absorption and EPR data. The assignment of these effects to the carboxylate moiety of p-(chloromercuri)benzoate is brought out by the observation that the introduction in the 3-fold channel of the benzene ring only by means of phenylmercuric acetate has no effect on the initial iron uptake kinetics and on the spectroscopic properties of the Fe(III)-apoferritin complex.
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PMID:Identification of the iron entry channels in apoferritin. Chemical modification and spectroscopic studies. 253 62

Diagnostic evaluation of the various forms of iron overload requires information about the total amount and distribution of iron stores. Direct information on the quantity of storage iron can be obtained only by its mobilization in response to repeated phlebotomy or after dilution of a labelled iron test dose in the total body iron pool. Both approaches are cumbersome and time-consuming and are suitable only for research purposes. Detailed information on the amount and distribution of tissue iron in iron overload can be obtained from biopsy specimens of the major iron storage organs such as the liver and bone marrow. However, the invasive nature of these procedures limits their clinical usefulness. Indirect measures, such as serum iron concentration, TIBC saturation, serum ferritin, chelate-induced urinary iron excretion or intestinal iron absorption, and ferrokinetic measurements may provide useful information on the amount of total body iron reserve. However, they all have important limitations in their diagnostic use for evaluating iron overload. The most suitable indirect storage iron index among these methods is the ferritin assay, which has a well established place in the diagnosis of iron overload and monitoring of the effect of therapy. Recent developments in physical methods such as CT, SQUID and NMR have significantly improved the applicability of these techniques for non-invasive measurement of liver iron. It is expected that quantitative measurement of hepatic iron stores will soon be integrated into the diagnostic procedures available by imaging techniques such as CT and NMR. In combination with screening parameters such as serum ferritin and TIBC saturation these new but expensive diagnostic tools may simplify and shorten the diagnostic process and may also be useful for monitoring the treatment of iron overload by phlebotomy or chelating drugs.
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PMID:Diagnosis and clinical evaluation of iron overload. 266 Sep 33

Polynuclear iron complexes of Fe(III) and phosphate occur in seawater and soils and in cells where the iron core of ferritin, the iron storage protein, contains up to 4500 Fe atoms in a complex with an average composition of (FeO.OH)8FeO.OPO3H2. Although phosphate influences the size of the ferritin core and thus the availability of stored iron, little is known about the nature of the Fe(III)-phosphate interaction. In the present study, Fe-phosphate interactions were analyzed in stable complexes of Fe(III).ATP which, in the polynuclear iron form, had phosphate at interior sites. Such Fe(III).ATP complexes are important not only as models but also because they may play a role in intracellular iron transport and in iron toxicity; the complexes were studied by extended x-ray absorption fine structure, EPR, NMR spectroscopy, and measurement of proton release. Mononuclear iron complexes exhibiting a g' = 4.3 EPR signal were formed at Fe:ATP ratios less than or equal to 1:3, and polynuclear iron complexes (Fe greater than or equal to 250, EPR silent at g' = 4.3) were formed at an Fe:ATP ratio of 4:1. No NMR signals due to ATP were observed when Fe was in excess (Fe:ATP = 4:1). Extended x-ray absorption fine structure analysis of the polynuclear Fe(III).ATP complex was able to distinguish an Fe-P distance at 3.27 A in addition to the octahedral O at 1.95 A and 4-5 Fe atoms at 3.36 A. The Fe-O and Fe-Fe distances are the same as in ferritin, and the Fe-P distance is analogous to that in another metal-ATP complex. An observable Fe-P environment in such a large polynuclear iron cluster as the Fe(III).ATP (4:1) complex indicates that the phosphate is distributed throughout rather than merely on the surface, in contrast to earlier models of chelate-stabilized iron clusters. Complexes of Fe(III) and ATP similar to those described here may form in vivo either as normal components of intracellular iron metabolism or during iron excess where the consequent alteration of free nucleotide triphosphate pools could contribute to the observed toxicity of iron.
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PMID:Fe(III).ATP complexes. Models for ferritin and other polynuclear iron complexes with phosphate. 298 69

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.
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PMID:Nuclear magnetic resonance study of iron overload in liver tissue. 407 75

The NMR relaxation technique was used to investigate the permeation of molecules into the cavity of ferritin. Spin-lattice relaxation times in the rotating frame of various probe molecules were measured for solutions of recombinant horse L-apoferritin without iron and horse spleen apoferritin with very small amounts of ferric ions. The results show that molecules larger than the size of the ferritin channels can pass through the channels into the ferritin interior, and that the maximum size of molecules for the permeation is smaller than maltotriose.
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PMID:Permeation of small molecules into the cavity of ferritin as revealed by proton nuclear magnetic resonance relaxation. 771 84

Horse spleen ferritin (HoSF) reconstituted with small iron cores ranging in size from 8 to 500 iron atoms was studied by magnetic susceptibility and pH measurements to determine when the added Fe3+ begins to aggregate and form antiferromagnetically coupled clusters and also to determine the hydrolytic state of the iron at low iron loading. The Evans NMR magnetic susceptibility measurements showed that at iron loadings as low as 8 Fe3+/HoSF, at least half of the added iron atoms were involved in antiferromagnetic exchange interactions and the other half were present as isolated iron atoms with S = 5/2. As the core size increased to about 24 iron atoms, the antiferromagnetic exchange interactions among the iron atoms increased until reaching the limiting value of 3.8 Bohr magnetons per iron atom, the value present in holo HoSF. HoSF containing eight or more Fe3+ to which eight Fe2+ were added showed that the Fe2+ ions were at sites remote from the Fe3+ and that the resulting HoSF consisted of individual, noninteracting Fe2+ and the partially aggregated Fe3+. pH measurements for core reduction showed that Fe(OH)3 was initially present at all iron loadings but that in the absence of iron chelators the reduced iron core is partially hydrolyzed. Proton induced x-ray emission spectroscopy showed that Cl- is transported into the iron core during reduction, forming a stable chlorohydroxy Fe(II) mineral phase.
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PMID:Iron core formation in horse spleen ferritin: magnetic susceptibility, pH, and compositional studies. 779

Iron regulatory elements (IREs) are a family of 28 nucleotide, non-coding elements which regulate the translation of ferritin mRNA (iron storage), erythroid delta-aminolevulinic acid synthase mRNA (heme synthesis) and the stability of the transferrin receptor (TfR) mRNA (iron uptake). IREs in the 5' end control translation (ribosome binding) and IREs in the 3' end control turnover (degradation). The specific regulator protein, the IRE-BP, is a member of the aconitase family but binds RNA only in the apo form without the Fe-S cluster. Cellular iron alters the IRE/IRE-BP interaction leading to translation of ferritin and eALAS mRNAs but degradation of the TfR mRNA. IRE function requires proximity to the 5' cap, achieved either by a short leader (eALAS) or a long, base-pairing flanking region (FL) (ferritin); a conserved triplet of FL base pairs enhances repression of ferritin mRNA. TfR mRNA has five AU-rich IREs which can also form an alternate structure with inter-IRE base pairs, in the absence of the IRE-BP. Ferritin IREs regulate both translation repression (negative control-IRE-BP dependent) and enhancement (positive control-initiation factor dependent); IRE-BP binding induces conformational changes in the FL. IREs use CAGUGU/C to form a hairpin loop with specific variations in the stem such as internal or bulge loops. A current structural model obtained using metallonucleases (1,10-phenanthroline-Cu, Fe-EDTA, Fe-bleomycin) and a preliminary analysis of the NMR spectrum, is a distorted helix with folds. The effect of cellular iron, Fe-S clusters and heme on the IRE-BP/RNA is not completely understood.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The IRE (iron regulatory element) family: structures which regulate mRNA translation or stability. 834 79

Noncoding sequences regulate mRNA and DNA function. IREs are a highly conserved family of noncoding mRNA sequences which coordinate ferritin mRNA translation and transferrin receptor mRNA stability by interactions with specific negative regulator protein, the IRP. RNA interactions with the IRP are modulated by cellular iron. The protein IRP binds to the entire IRE causing conformational changes in flanking region [Harrell et al. (1991) PNAS 88:4166-4170). The IRE+FL is the first RNA element encoding both positive and negative translational control and serves as a model mRNA regulatory elements. Folding of the IREs indicated previously by reactivity with chemical and enzymatic probes [E.C Theil (1994) Biochem. J., 304:1-11) is confirmed by using 1H, 15N and 31P (1) NMR) and CD to show that IRE secondary structure [hairpin-hexaloop (HL)/stem/internal loop or bulges] is folded, CD spectra display Mg2+ dependent structural changes in the temperature range used in the studies of IRE function. G/A substitution was shown by NMR and UV-vis to decrease stability of the folded IRE [H.Sierzputowska-Gracz et al. (1995) Nucl. Acids Res. 23:146-153]. A hairpin loop mutation affected only negative translational control.
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PMID:15N NMR and CD studies of the IRE (iron regulatory element in ferritin mRNA with single base substitution in the hairpin loop. 864 70


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