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

Iron is essential to cell proliferation. Its uptake by cells requires specific binding of the major serum iron-transport protein, transferrin, to cell surface transferrin receptors, followed by endocytosis of the receptor-ligand complexes and release of iron from endosomal vesicles to the cytoplasm. The structural and functional aspects of this pathway are reviewed. Intracellular iron either serves as a substrate for the biosynthesis of haem and iron-containing proteins or is stored in ferritin deposits. Recent studies are presented which establish that iron plays an important role in the maintenance of its own homeostasis by regulating coordinately the expression of both the transferrin receptor and ferritin. The elucidation of these regulatory mechanisms may become important to the understanding of certain disorders in iron-metabolism.
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PMID:The transferrin receptor: a key function in iron metabolism. 267 49

There has been a continuous refinement over the past several decades of methods to detect iron deficiency and assess its magnitude. The optimal combination of measurements differs for clinical and epidemiological assessment. Clinically, the major problem is to distinguish true iron deficiency from other causes of iron-deficient erythropoiesis, such as the anaemia of chronic disease. Epidemiologically, techniques that provide quantified estimates of body iron are preferable. For both purposes, the serum ferritin is the focal point of the laboratory detection of iron deficiency. Serum ferritin measurements provide a reliable index of body iron stores in healthy individuals, a cost-effective method of screening for iron deficiency, and a useful alternative to bone marrow examinations in the evaluation of anaemic patients. Preliminary studies indicate that measurement of the serum transferrin receptor may be the most reliable way to assess deficits in tissue iron supply.
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PMID:Iron deficiency: definition and diagnosis. 268 11

Over the last 10 years there has been steady progress in our understanding of the structure of the iron-binding proteins transferrin and ferritin, and the transferrin receptor. In the last few years there have been very rapid developments in understanding of the genetics of these proteins and the regulation of synthesis. This review includes a description of gene localization and structure, the regulation of protein synthesis and the structure of proteins of the transferrin family, the transferrin receptor and the iron storage protein ferritin.
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PMID:An overview of iron metabolism at a molecular level. 268 15

Iron-responsive elements (IREs) are RNA motifs that have been identified within the 5' untranslated region of ferritin messenger RNA and the 3' untranslated region of transferrin receptor mRNA. A single IRE mediates iron-dependent control of ferritin translation, whereas multiple IREs are found in the region of the transferrin receptor mRNA responsible for iron-dependent control of mRNA stability. A cytosolic protein binds in vitro to the IREs of both mRNAs. The IRE-binding protein (IRE-BP) is shown to require free sulfhydryl groups for its specific interaction with the IRE. Treatment of lysates with reducing agents increases the binding activity, whereas agents that block sulfhydryls inhibit binding. Iron starvation, leading to decreased ferritin translation, results in increased binding activity, which is explained by an increase in the fraction of the IRE-BP that is in a fully reduced state.
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PMID:Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction. 271 Nov 87

Recombinant clones of the chicken transferrin receptor gene and cDNA have been isolated and sequenced. Two highly conserved regions have been identified in the 3' noncoding sequence of the human and chicken TR gene. The conserved regions include sequences that have been shown to be involved in the iron-dependent regulation of human TR mRNA stability. These sequences can be modeled as two different types of RNA secondary structures, one containing stem-loop structures that are similar to the iron-responsive elements found in ferritin mRNA and the other being a stable, duplex/stem-loop structure. Both forms show considerable similarity between chicken and human mRNA. The expression of TR is developmentally regulated during erythroid maturation, and immature erythroid cells express exceptionally high levels of TR mRNA.
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PMID:Chicken transferrin receptor gene: conservation 3' noncoding sequences and expression in erythroid cells. 273 2

Iron regulates human transferrin receptor (hTR) expression by modulating the stability of cytoplasmic hTR mRNA. This regulation requires a distinct secondary structure in the mRNA 3' untranslated region. We identified a specific cytoplasmic factor that binds simultaneously to four homologous palindromes within the regulatory domain. Iron chelator induced the RNA binding activity 25-fold in parallel with mRNA. Upon the addition of iron salts, a rapid decay of factor activity closely preceded hTR mRNA degradation, indicating a causal relation. Induction and decay occurred posttranscriptionally. Binding of the factor to hTR mRNA palindromes was competed by 5' regulatory sequences of ferritin mRNA, which are responsible for iron-dependent translational control. These results suggest that cellular iron maintains its homeostasis by coordinate regulation of hTR and ferritin expression via a common factor.
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PMID:A specific mRNA binding factor regulates the iron-dependent stability of cytoplasmic transferrin receptor mRNA. 275 28

Three human mRNAs are regulated post-transcriptionally by iron via iron-responsive elements (IREs) contained in each mRNA. A cytoplasmic protein (IRE-BP) binds to these cis-acting elements and mediates the translational regulation of ferritin H- and L-chain mRNA and the iron-dependent stability of transferrin receptor (TfR) mRNA. We have taken advantage of the different mobilities of the human and rodent IRE/IRE-BP complexes on non-denaturing polyacrylamide gels to determine the chromosomal localization of the gene encoding the IRE-BP. Utilizing a panel of 34 different human/rodent hybrid cell lines we have assigned the IRE-BP gene to human chromosome 9. This new technique based on nucleic acid/protein interaction may allow determination of the chromosomal localization of other RNA- or DNA-binding proteins.
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PMID:Chromosomal localization of nucleic acid-binding proteins by affinity mapping: assignment of the IRE-binding protein gene to human chromosome 9. 277 41

Hepatocyte iron release was studied in vivo in rats. After the injection of iron 59-labeled ferritin, hemoglobin, or human asialotransferrin, the proportions of the radioactive iron returned to the plasma and incorporated into stores were determined under various conditions. Iron 55-labeled rat transferrin was injected at the same time as the 59Fe-labeled compound, and storage iron release was calculated from the cumulative incorporation of the two isotopes in the red cell mass over 2 weeks. The various 59Fe-labeled compounds were processed differently by the hepatocyte, but the radioactive iron was incorporated in the same iron stores. About 6% of the hepatocyte storage iron was released daily in normal rats, but a pool of iron that is not mobilized spontaneously was clearly identified in iron overload. Iron turnover in the hepatocyte was regulated by the rate of erythropoiesis and iron status of the animal, and inflammation blocked hepatocyte iron release. A strong correlation between hepatocyte iron release and plasma transferrin receptor levels was observed (p less than 0.001), suggesting that plasma transferrin receptors could mediate the regulation of hepatocyte iron mobilization in rats.
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PMID:Hepatocyte iron release in rats. 292 42

In previous studies, antitransferrin receptor antibody 42/6 inhibited growth of normal granulocyte/macrophage progenitors and some malignant myeloid cells. In these studies, leukemia cell lines cultured without serum and fresh leukemia cells were used to investigate the roles of Fe, transferrin receptors, and transferrin in leukemia cell growth, and mechanisms of 42/6 inhibition and resistance. HL60 and KG-1 leukemia cells grown in serum-free medium were inhibited by 42/6. In contrast to results in fetal calf serum (FCS), soluble Fe (ferric nitriloacetate) reversed 42/6 growth inhibition of serum-free HL60 cells. When HL60 cells were adapted for growth in serum-free, transferrin-free medium, they became refractory to 42/6 growth inhibition. By using radiolabeled transferrin and 42/6, HL60 cells cultured in FCS and transferrin displayed similar quantities of transferrin receptors (29,000-30,000/cell) and similar Kd's (3.8-4.9 X 10(-9) M). Cells grown in transferrin-free medium showed a similar Kd (3.1 X 10(-9) M), but fewer transferrin binding sites (5,000/cell). Transferrin-independent cells contained a log higher concentration of intracellular ferritin. For both FCS and serum-free HL60 cells, calculated affinities for 42/6 were lower (5.7-10.0 X 10(-9) M), but the number of binding sites was three- to fourfold higher. To investigate further the relationship between receptor display and antibody inhibition in proliferating normal and malignant myeloid cells, simultaneous immunofluorescence was used to determine the cell cycle status of transferrin receptor-positive cells. Malignant cells in S + G2/M displayed approximately 50% of the amount of transferrin receptors detected in normal dividing colony-stimulating factor-stimulated marrow cells. Receptor display by dividing cells from two patients with acute nonlymphocytic leukemia was variable. When HL60 cells were exposed to dimethyl sulfoxide, transferrin receptor display decreased, and 42/6 growth inhibition was abrogated or greatly diminished. The presence of 42/6 did not prevent dimethyl sulfoxide-induced HL60 differentiation in serum-containing or serum-free cultures. We conclude that human leukemia cells require Fe for growth and that 42/6 inhibits transferrin-dependent cells by Fe deprivation. Some dividing normal and differentiating malignant cells display reduced transferrin receptors, and can also escape antibody inhibition. The increased ferritin levels and decreased transferrin receptors in transferrin-independent HL60 cells confirm the inverse relationship between cell ferritin content and transferrin receptor display. These studies indicate a critical role for Fe in leukemia cell growth and possible roles in cellular differentiation.
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PMID:Role of transferrin, Fe, and transferrin receptors in myeloid leukemia cell growth. Studies with an antitransferrin receptor monoclonal antibody. 298 53

Picolinic acid, a metal chelating molecule, was administered to human erythroleukaemic cell lines (K 562 and HEL) that were grown in serum-containing media. Picolinic acid inhibited both iron uptake and cell growth. Furthermore, picolinic acid was shown to markedly decrease the level of ferritin in the cells. In spite of the inhibition of cell growth, picolinic acid induced a marked increase in the transferrin-binding capacity of the cells. This phenomenon was due to a two-five-fold enhancement of the rate of transferrin receptor biosynthesis. Other iron-chelating compounds, capable of reducing the level of intracellular iron, also elicited a marked enhancement of the transferrin-binding capacity of the cells. However, the addition of iron, as ferric ammonium citrate, in the culture medium elicited a marked increase in the level of ferritin and a strong decrease in the transferrin-binding capacity of the cells. On the basis of these data we propose that a feed-back mechanism is involved in the regulation of transferrin receptors: when the cells accumulate iron they decrease the number of transferrin receptors in order to prevent further accumulation of iron; when no or low iron is available to the cells, the number of transferrin receptors markedly increases as a compensatory mechanism.
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PMID:The iron-chelating agent picolinic acid enhances transferrin receptors expression in human erythroleukaemic cell lines. 299 May 22


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