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

Intracellular iron homeostasis is modulated by ferritin and transferrin receptor (TfR). And the biosynthesis of both proteins is regulated post-transcriptionally by the interaction of specific cytoplasmic protein, termed iron responsive elements-binding protein (IRE-BP) with specific sequences, termed iron responsive elements (IRE), located in the 5' untranslated region (UTR) of the ferritin mRNA or 3'UTR of TfR mRNA. In spite of the important role of IRE/IRE-BP interaction for cellular iron metabolism, the role of it for erythroid differentiation is not yet well known. In this study, the author investigated the time sequential change of IRE-BP, ferritin and TfR mRNA expression and the binding activity of IRE-BP with IRE during erythroid differentiation of human erythroleukemic cells (K 562). During erythroid differentiation of K 562 cells by Na-butyrate, analysis using reverse transcription-polymerase chain reaction indicated that TfR mRNA expression was little changed. The addition of excess iron (as 100 micrograms/ml holo transferrin) caused reduction of the level of TfR mRNA, however, the iron chelator defferoxamine caused its increase. IRE-BP mRNA was slightly increased at the early period of erythroid differentiation and unaffected by iron or iron chelator treatment. Affinity binding signal of IRE and IRE-BP detected by gel retardation assay was also increased at the early period of erythroid differentiation. The addition of iron or iron chelator both caused marked increase in the binding activity of IRE-BP at 48 hr after Na-butyrate treatment. These results suggest that IRE/IRE-BP inter-action may play a possible role in the erythroid differentiation of K562 cells.
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PMID:[An analysis of the iron related proteins during erythroid differentiation in K562 cells]. 795 92

Iron regulatory factor (IRF) is a cytoplasmic mRNA-binding protein with specificity for iron-responsive element (IRE) RNA stem-loops. IRF post-transcriptionally regulates intracellular iron levels via binding to IREs in the untranslated regions of ferritin, transferrin receptor, and erythroid 5-aminolevulinic-acid synthase mRNAs. Specific IRE nucleotides are phylogenetically conserved: those of the 6-base loop (5'-CAGUGN-3') and an unpaired "bulge" cytosine. We prepared a pool of 16,384 IRE molecules randomized at these seven nucleotide positions and employed in vitro selection to identify RNAs that bind human IRF. Two major classes of high affinity RNA ligands were selected; the optimal loop sequences of each are 5'-CAGUGN-3' (wild type) and 5'-UAGUAN-3'. This novel finding predicts base pairing within the IRE loop between positions 1 and 5, thus facilitating the formation of a specific loop structure in which nucleotides at positions 2-4 are made accessible for protein interaction. Nucleotide substitution at these loop positions, or at the position of the bulge cytosine, decreased binding by 36-99%. In addition, we demonstrate a preferred IRE bulge structure and report a striking difference in the RNA binding specificity of rat IRF compared with that of the related IRE-binding protein, IRFB.
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PMID:Optimal sequence and structure of iron-responsive elements. Selection of RNA stem-loops with high affinity for iron regulatory factor. 802 Dec 54

The interaction of extracellular human isoferritins with normal erythroid precursors developing in a two-phase liquid culture was studied. Cells at the stage of polychromatic normoblasts exhibited substantial specific binding of radioiodinated placental isoferritins. Considerably more acidic isoferritin was bound than basic isoferritin. The binding of ferritin was significantly higher at 37 degrees C than at 4 degrees C. All of the 125I-acidic isoferritin bound at 4 degrees C, but only part of that bound at 37 degrees C, could be dislodged by the addition of 500-fold excess of non-labelled acidic isoferritin. Acidic isoferritin displaced radio-iodinated acidic isoferritin from the erythroid cells more efficiently than intermediate or basic isoferritins. Kinetic analysis suggests a dissociation constant (Kd) of 3.9 x 10(-8) M for acidic ferritin and 3.7 x 10(-7) M for basic isoferritin. The average number of binding sites for acidic isoferritin was 1.3 x 10(5) per cell. The results point to specific binding and receptor-mediated internalization for predominantly acidic isoferritin by developing human erythroid cells.
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PMID:Binding and uptake of exogenous isoferritins by cultured human erythroid precursor cells. 804 47

Ferritin synthesis is regulated at the translational level by iron, but it is likely that transcriptional regulation of H and L genes is responsible for tissue-specific distribution of H and L mRNAs. In order to define the regions important for transcriptional regulation of the mouse ferritin H gene, we have linked the promoter, including the transcription start site, and 5 kilobases of upstream sequence to a reporter gene (human growth hormone). This construct and a series of 5' deletion mutants have been used to transfect erythroid (K562, mouse erythroleukemia (MEL)) and hepatoma (HepG2) cell lines. Measurement of growth hormone in the culture medium and analysis of ferritin-growth hormone transcripts by a ribonuclease protection assay revealed that a 140-base pair minimal promoter is sufficient to confer a high level of expression to the reporter gene in both cell types. In addition, a 180-base pair fragment, lying 4.5 kilobases upstream of the ferritin transcription start site, functions like an inducible enhancer during N,N'-hexamethylene-bis-acetamide-induced differentiation of MEL cells. A perfect match to a consensus binding motif to the erythroid transcription factor NF-E2 is present in this regulatory element, but the mutant NF-E2 enhancer retains the inducible activity in stably transfected MEL cells, and the results from gel retardation assays suggest that protein-DNA complexes that form in vitro between the ferritin enhancer and MEL nuclear extracts do not contain NF-E2. Thus, nuclear factors that mediate inducibility of the ferritin enhancer remain to be identified.
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PMID:Mouse ferritin H subunit gene. Functional analysis of the promoter and identification of an upstream regulatory element active in erythroid cells. 805 Nov 21

Translation of ferritin and erythroid 5-aminolevulinate synthase (eALAS) mRNAs is regulated by iron via mRNA-protein interactions between iron-responsive elements (IREs) and iron regulatory protein (IRP). In iron-depleted cells, IRP binds to single IREs located in the 5' untranslated regions of ferritin and eALAS mRNAs and represses translation initiation. The molecular mechanism underlying this translational repression was investigated using reconstituted, IRE-IRP-regulated, cell-free translation systems. The IRE-IRP interaction is shown to prevent the association of the 43S translation pre-initiation complex (including the small ribosomal subunit) with the mRNA. Studies with the spliceosomal protein U1A and mRNAs which harbour specific binding sites for this protein in place of an IRE furthermore reveal that the 5' termini of mRNAs are generally sensitive to repressor protein-mediated inhibition of 43S pre-initiation complex binding.
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PMID:Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs. 807 Apr 15

Erythroid cells regulate heme biosynthesis in a manner that is distinct from all other cell types. While heme negatively regulates the synthesis of the housekeeping delta-aminolevulinate synthase (ALAS-N) in all non-erythroid cells, the expression of an erythroid-specific isozyme (ALAS-E) is developmentally regulated in red blood cells. As a first step towards understanding the molecular basis for the transcriptional regulation of ALAS-E during erythropoiesis, we cloned and characterized the chicken ALAS-E locus. This gene spans 18 kbp and is composed of eleven exons. The intron/exon structure of erythroid ALAS was found to be conserved among several vertebrate species. Direct RNA sequencing identified a 5' untranslated region that is derived from two continuous exons and is predicted to form a very stable stem-loop structure that bears resemblance to the ferritin iron-responsive element. Tissue-specific expression of the ALAS-E gene was analyzed by transient transfection assays in hematopoietic cells of both erythroid and non-erythroid origins. These experiments identified distal (-784 to -505 bp) and proximal (-155 to +21 bp) promoter elements which are required for high level, erythroid-specific transcription.
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PMID:Structure and regulation of the chicken erythroid delta-aminolevulinate synthase gene. 816 37

Red cell ferritin is a residue of erythroblast ferritin. It reflects the balance between the iron supply to the erythroid marrow and the need for haemoglobin synthesis. Erythrocyte ferritin can be measured in haemolysates after discarding plasma and leucocytes by different methods. The decrease in erythrocyte ferritin content indicates manifest iron deficiency anaemia. Ferritin levels do not appear to be influenced by inflammation, infection, tissue necrosis or tumors and may be a reliable indicator of iron status in inflammatory diseases. Erythrocyte ferritin is markedly increased in patients with iron overload allowing early diagnosis of hereditary haemochromatosis and the monitoring of phlebotomy therapy. Finally, in some pathologies erythrocyte assay is a more reliable indicator of the iron status than serum ferritin.
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PMID:[Erythrocyte ferritin]. 817

Nine patients with anemia of chronic renal failure were treated with recombinant human erythropoietin (rHuEPO) in dose 50-150 IU/kg/week. After 8 weeks the treatment was maintained with 30-50 IU/kg/week for one year. A significant increase of hemoglobin (Hb) level and red blood cell (RBC) count was observed in all patients. Administration of rHUEPO maintained Hb level higher than 100 milligrams and RBC count above 3.0 x 10(12)/l. Iron stores decreased in all patients. Parameters reflecting either the real amount of iron available for erythropoiesis or iron stores in erythroid precursors, i.e. red cell ferritin (eF), free erythrocyte protoporphyrin (FEP) and transferrin saturation (satTRF) were the most reliable tools for diagnosis of iron deficient erythropoiesis. Serum ferritin (sF) was not decreased in most patients, however, sF level was below 50 micrograms/l in all patients at the time of diagnosis of iron deficiency. Iron supplementation in a daily dose allowing absorption of 100mg of elementary iron was sufficient to cover the increased demand for iron in rHuEPO treated patients.
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PMID:[Iron stores in patients with chronic kidney failure treated with recombinant human erythropoietin]. 818 71

Anemia is a common complication of patients with multiple myeloma (MM) and myelodysplastic syndrome (MDS). Most of these patients often require blood transfusion. 12 patients, including 7 cases of MM and 5 cases of MDS, were treated with rhEPO 10,000 micrograms three times a week for 15 weeks. The hemoglobin in 6 of 7 cases of MM steadily increased and eventually reached normal level without blood transfusion. The number of erythroid precursors in bone marrow was increased significantly and serum ferritin concentration was decreased gradually during EPO administration. However 5 patients with MDS did not show any response to EPO. The adverse side effects were hardly observed in any patients received EPO treatment. It is suggested that rhEPO is a promising preparation for treating MM-associated anemia rather than MDS-associated anemia.
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PMID:[Erythropoietin treatment of anemia associated with multiple myeloma (MM) and myelodysplastic syndrome (MDS)]. 822 21

Inflammatory low iron is the second cause, after true iron deficiency, of acquired anaemia. It is mainly due to insufficient erythropoiesis resulting from inhibition of the erythroid progenitor and to disturbances in the synthesis and action of erythropoietin. These changes seem to be dependent on factors, such as TNF-alpha, interleukin-1 and interferon-gamma, which are released in inflammatory processes. Alterations in iron metabolism seem to be secondary, but also partly provoked by the same inhibitory agents. All these anaemias share a common character, i.e. lowering of serum iron level without increase of transferrin level, while plasma ferritin level is within normal limits. In addition to symptomatic therapy by red cell transfusions, numerous trials have shown that recombinant erythropoietin is effective in the treatment of the anaemia that accompanies cancers, chronic inflammatory and rheumatic diseases and of the anaemia provoked by HIV infection.
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PMID:[Inflammatory hyposideremic anemia]. 823 81


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