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

Bone marrow sideroblast counts were found to be persistently depressed to between 0 and 30 per cent in 24 uremic patients with residual renal tissue undergoing chronic dialysis therapy. Marrow sideroblastopenia notwithstanding, sideroblast counts in these subjects correlated well with iron balance, being respectively 6.6 +/- 0.8 (S.E.M.) per cent in iron depleted, and 18.2 +/- 1.7 per cent in iron-repleted individuals (p less than 0.0005). Following bilateral nephrectomy a persistent relative marrow sideroblastosis developed, counts reaching values of 46.5 +/- 3.1 per cent on average. It is suggested that this sideroblastosis is a response to reduced heme synthesis and reflects the iron removal function of ferritin granules within erythroid cells.
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PMID:The relationship between bone marrow sideroblasts and iron deficiency in chronically hemodialyzed uremic subjects. 87 Nov 36

The distribution of receptors for concanavalin A (Con A) and anionic groups on plasma membranes of developing blood cells was investigated in the rat. Glutaraldehyde-fixed bone marrow and circulating blood cells were exposed to ferritin-conjugated Con A or positively chaged ferric oxide (CI) and processed for electro n microscopy. The frequency of Con A and CI binding sites varied during different erythroid developmental stages and amont different leukoid cell types. There was a constant inverse relationship between Con A and CI binding sites. Among leukoid cells, Con A binding was high on plasma cells and macrophages, lower on neutrophils and lymphocytes, and still lower on eosinophils and basophils; CI binding was highest in the latter and lowest in plasma cells and macrophages. Among erythroid cells, there was a progressive increase in Con A and a decrease in CI binding after successive divisions of erythroblasts, and a progressive decrease in Con A and an increase in CI binding upon maturation of the orthochromatic erythroblast to the reticulocyte. The most pronounced modification in distribution of these sites occurred during nuclear expulsion: that protion of the plasma membrane surrounding the extruded nucleus was heavily labeled by Con A (up to four times that of the orthochromatic erythroblast) whereas the reticulocyte had considerably fewer sites. The situation was reversed with CI. The results suggest that the concentration of nonsialated glycoproteins (to which Con A binds) varies inversely to that of sialoproteins (to which CI binds) in the membrane of the differentiating erythroid cell. The remarkable changes observed at the time of nuclear extrusion suggest that there is either local modification of glycosylated groups with removal of sialyl residues from the membrane surrounding the extruded nucleus of selective segregation of membrane glycoproteins leading to a high concentration of sialoproteins (glycophroin) in the membrane of the mature erythrocyte.
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PMID:Variations in distribution of con A receptor sites and anionic groups during red blood cell differentiation in the rat. 97 48

This paper reviews and reports the results of experiments on the mechanism by which iron is delivered from extracellular transferrin to reticulocyte mitochondria in which haem is synthesized. It is suggested that transferrin donates the iron directly to mitochondria. Transferrin seems to be bound to mitochondria during the process of iron release. When the release of iron from transferrin is blocked by haem, the iron-transferrin complex remains bound to mitochondria so that the total amount of transferrin molecules associated with mitochondria increases in haem-treated reticulocytes. This also leads to an increase in the number of transferrin molecules in the cytosol. In haem-deficient reticulocytes, the rate of dissociation of iron from transferrin is accelerated and the uptake of iron by mitochondria is increased. When the synthesis of haem is inhibited, the non-haem iron in the cytosol (i.e. mainly low-molecular-weight and ferritin iron) comes from mitochondria. Greater amounts of non-haem iron can also be induced in reticulocytes incubated with highly saturated transferrin but, in this case, iron does not seem to be accumulated in mitochondria. These results represent an experimental basis for the elucidation of the excessive non-haem iron accumulation in erythroid cells observed in various clinical conditions.
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PMID:Control of iron delivery to haemoglobin in erythroid cells. 105 29

Ferritin receptors are present on the membranes of many normal and malignant cells. The binding specificity of these receptors for H and L subunits was examined using recombinant human ferritin homopolymers. At least two different types of ferritin receptors were found, one derived from normal rat, pig, and human liver which shows similar binding of H- and L-ferritin. The second receptor type, specific for the H-chain ferritin, has been identified on membranes of hepatic and other transformed cells, and of normal lymphoblasts and erythroid precursors. These two receptor types may have different metabolic functions: the hepatic receptor acting as a scavenger for circulating ferritin and possibly for iron exchange between hepatocytes and macrophages; the H-ferritin receptor having a regulatory role which is not directly related to iron metabolism. The expression of the H-ferritin receptor is closely related to the activation and proliferation state of the cells. Addition of H-ferritin to the culture medium of cells expressing the H-ferritin receptor resulted in inhibition of cell proliferation and of colony formation.
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PMID:Functional roles of the ferritin receptors of human liver, hepatoma, lymphoid and erythroid cells. 133 22

The hematologic findings of chronic renal failure are consistent with hypoproliferative anemia; the pathogenesis of the anemia is primarily due to decreased erythropoietin production by the diseased kidneys. There are aggravating factors (AF) contributing to this primordial cause: inhibitors to erythroid marrow function, shortened red cell survival, nonevident chronic blood loss (owing to uremic platelet dysfunction), iron and/or folate deficiency, aluminium toxicity, hemolysis (acute or chronic), etc. Ten patients with end stage renal disease, treated with maintenance hemodialysis and high transfusional requirement (more than 300 ml/month) are presented; in five the AF were discarded by a previously presented protocol (Table 1) and they were treated with human recombinant erythropoietin (r-HuEPO) intravenously, in conventional schemes (three times a week) and doses (195 +/- 41 Units/Kg)-Group A-. The AF were not studied in the other five and the r-HuEPO treatment employed different doses (125 +/- 70 U/K/W) and protocols (1.7 +/- 0.5 times a week)-Group B-(Table 2). The transfusional requirement disappeared and the hematocrit and the hemoglobin rose significantly in both groups (more in group A) (Table 3). The significant drop in ferritin levels (147 +/- 30 ng/ml vs 27.5 +/- 11 ng/ml at the 12th week) and the stabilization in reticulocyte count (1.4% at start vs 2% at 12th week) indicate iron consumption; in the meantime, the persistent increment in reticulocyte production index (1 at start vs 3 at 12th week) revealed a continuous stimulation of the erythropoiesis (Fig. 1). No clinical and/or vascular complications were observed; arterial pressure and serum potassium levels did not rise significantly so that r-HuEPO treatment was not canceled in any case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The correction of anemia with a high requirement for transfusion in patients on maintenance hemodialysis by conventional and reduced doses of recombinant human erythropoietin]. 134 Sep

Human H-ferritin homopolymer was denatured in sodium dodecyl sulphate and injected in mice to obtain antibodies for dissociated H-subunit. The antisera and Moabs obtained were specific for the denatured H-chain with no cross-reactivity with assembled ferritins in immunoblotting experiments. In contrast the Moabs for native recombinant H-ferritin are specific for the assembled ferritin molecules with weak cross-reactivity with the denatured H-subunits. The epitope recognized by one of the anti-denatured H-chain Moabs was mapped on the C-terminal helix of ferritin. The antibodies were used to study H-ferritin conformation in cells. In immunocytochemistry experiments the antibodies for denatured H-ferritin stained HeLa and K562 cells weakly, with a different intensity and pattern to those obtained with anti-native H-ferritin antibody. In human bone marrow smears the anti-denatured ferritin antibodies stained only reticuloendothelial cells, and did not recognize the H-ferritin rich immature erythroblasts. It is concluded that assembled and denatured H-ferritins are immunogenically distinct, and that erythroid and reticuloendothelial cells within the bone marrow contain H-ferritin in different conformations.
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PMID:Antibodies for denatured human H-ferritin stain only reticuloendothelial cells within the bone marrow. 138 4

The mechanisms responsible for anaemia in leprosy were studied prior to the institution of therapy in 56 patients with active disease. Haematological indices, iron-related measurements, inflammatory markers and erythropoietin levels were assessed, with bone-marrow studies being performed on anaemic patients. Anaemia was more common in the patients with lepromatous leprosy (85.7%) than it was in the rest of the group (19%). The lepromatous group exhibited the disordered iron transport of the anaemia of chronic disorders in that they had a significantly lower mean serum iron level (P less than 0.05), and a mildly raised serum ferritin concentration. Anaemic lepromatous patients also showed a blunted erythropoietin response compared with controls with non-inflammatory anaemia. A subgroup of five anaemic subjects displayed apparently adequate transport of iron to the erythroid marrow (normal percentage transferrin saturations and appropriate sideroblast counts) and the blunted erythropoietin response appeared to be the dominant factor in the pathogenesis of their anaemia. Analysis of inflammatory markers revealed that while the erythrocyte sedimentation rate was very high in the lepromatous subjects, there was no concomitant rise in C-reactive protein concentration. This suggests the presence of a disordered cytokine-mediated acute phase response in the condition.
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PMID:Anaemia, iron-related measurements and erythropoietin levels in untreated patients with active leprosy. 140 25

Maintenance of cellular iron homeostasis demands the coordination of iron uptake, intracellular storage, and utilization. Recent investigations suggest that a single genetic regulatory system orchestrates the expression of proteins with central importance for all three aspects of cellular iron metabolism at the level of mRNA stability and translation. Two components of this regulatory system have been defined: a cis-acting mRNA sequence/structure motif called "iron-responsive element" (IRE) and a specific trans-acting cytoplasmic binding protein, here referred to as "IRE-binding protein" (IRE-BP). As an early event in the regulatory cascade, cellular iron deprivation induces the IRE-binding activity of IRE-BP, whereas binding activity is reduced in iron-replete cells. IRE-BP is highly homologous to the iron-sulphur (Fe-S) protein aconitase which strongly suggests that IRE-BP is an Fe-S protein itself. Control over IRE-BP activity by the cellular iron status is exerted post-translationally and likely involves changes between (4Fe-4S) and (3Fe-4S) states of the postulated IRE-BP Fe-S cluster. In addition, post-translational regulation of IRE-BP activity via heme has been proposed. Subsequent to its activation, IRE-BP binds with high affinity to single IREs contained in the 5' untranslated regions (UTRs) of ferritin and erythroid 5-aminolevulinic acid synthase (eALAS) mRNAs. The binding represses translation of these proteins involved in iron storage and utilization, respectively. In contrast, iron uptake is largely regulated via multiple IREs in the 3' UTR of transferrin receptor (TfR) mRNA. TfR-IREs are required for the iron-sensitive control of TfR mRNA stability. IRE-BP binding stabilizes TfR gene transcripts against as yet undefined ribonucleases. As a result of these regulatory interactions, iron starvation induces the expression of TfR, thereby increasing iron uptake, and represses the synthesis of proteins involved in iron storage and utilization. As cellular iron levels rise, the homeostatic balance is maintained by lowering iron uptake and increasing iron storage in ferritin.
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PMID:Coordination of cellular iron metabolism by post-transcriptional gene regulation. 143 80

The dose of recombinant human erythropoietin (r-HuEpo) required to correct anemia of end-stage renal disease varies among patients. The possible factors that interfere with the responsiveness to r-HuEpo were not completely known. In 32 patients on regular hemodialytic treatment with marked anemia (Hb 5.6 +/- 0.7 g/dl), we evaluated circulating erythroid progenitor cells [burst-forming-unit erythroid (BFU-E)], erythropoietin, ferritin, folate and 1-84-parathormone levels before r-HuEpo therapy. In 12 patients, the aluminum levels after deferoxamine were also evaluated. The possible correlation between these factors and the response to r-HuEpo therapy was then evaluated. The number of circulating (c) BFU-E was highly variable (521 +/- 447 colonies/ml of blood; normal level 742 +/- 192) and does not correlate with erythropoietin, ferritin, folate, 1-84-parathormone or aluminum levels. A direct correlation between basal cBFU-E and the responsiveness to r-HuEpo therapy was recorded while no correlation was found with the other analyzed parameters. We hypothesized that low basal cBFU-E (interleukin-3 deficiency?) could reduce the response to r-HUEpo because of failure of this hematopoietic stem cell compartment to replenish the pool of more mature erythropoietic progenitor cells during the phase of accelerated maturation induced by r-HuEpo.
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PMID:Circulating burst-forming-unit erythroid and the responsiveness to recombinant human erythropoietin in patients on regular hemodialytic treatment. 143 6

The iron-responsive element binding protein (IRE-BP) is a cytosolic protein that binds a highly conserved sequence in the untranslated regions of mRNAs involved in iron metabolism including ferritin, transferrin receptor, and erythroid 5-aminolevulinate acid synthase. This conserved sequence is termed the iron-responsive element and is necessary for the post-transcriptional regulation of these mRNAs by iron. The rat liver IRE-BP was purified to homogeneity by chromatographic methods and partial amino acid sequence was obtained. A cDNA was isolated from a rat liver cDNA library and sequenced. The amino acid sequence deduced from the cDNA sequence corresponds to a protein of 889 amino acids with a predicted molecular weight of 97.946. The NH2-terminal sequence obtained by Edman degradation matched the deduced amino acid sequence obtained from the cDNA, confirming the translational start site. Rat liver IRE-BP shares 95% identity with human IRE-BP and 98% identity with mouse IRE-BP indicating that the IRE-BPs have remained highly conserved during evolution. The 5'-untranslated region is at least 236 nucleotides and contains interesting structural features including two direct repeats, an inverted repeat, and three small open reading frames. The rat IRE-BP mRNA is approximately 3600 nucleotides and is expressed in a variety of rat tissues including liver, spleen, and gut. Over the course of 16 h following an intraperitoneal injection of iron in rats. IRE-BP RNA binding activity decreases to 50% of control levels. The decrease in IRE-BP RNA binding activity in extracts from iron-treated rats is reversible by pretreatment of the extracts with reducing agents. The steady-state levels of IRE-BP mRNA remain constant during iron treatment. These data suggest that the decrease in IRE-BP RNA binding activity by iron in rat liver is due to post-translational changes in the RNA binding affinity of the IRE-BP and not due a decrease in the transcription of the IRE-BP gene or to the destabilization of the IRE-BP mRNA.
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PMID:The iron-responsive element binding protein. Purification, cloning, and regulation in rat liver. 152 27


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