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

The effect of changes in iron availability and induction of differentiation on transferrin receptor expression and ferritin levels has been examined in the promonocytic cell line U937. Addition of iron (as 200 micrograms/ml saturated transferrin) or retinoic acid (1 microM) both caused approx. 70% reduction in the average number of surface transferrin receptors, while the iron chelator desferrioxamine caused an 84% increase. Comparable changes also occurred in the levels of transferrin receptor mRNA. Neither iron nor retinoic acid significantly altered the half-life of transferrin receptor mRNA in the presence of actinomycin D (approx. 75 min) but a 10-fold increase in stability occurred in the presence of desferrioxamine. Iron and retinoic acid both caused an increase in intracellular ferritin levels (approx. 4-and 3-fold, respectively), while desferrioxamine reduced ferritin levels by approx. two-thirds. The effect of iron and retinoic acid added together did not differ greatly from that of each agent alone. None of the treatments greatly affected levels of L-ferritin mRNA. Virtually no H-ferritin mRNA was detected in U937 cells. These results show that changes in ferritin and transferrin receptor caused by treatment with retinoic acid are similar to those induced by excess iron, and suggest that changes in these proteins during cell differentiation are due to redistribution of intracellular iron into the regulatory pool(s), rather than to iron-independent mechanisms.
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PMID:Effect of iron and retinoic acid on the control of transferrin receptor and ferritin in the human promonocytic cell line U937. 173 56

Iron regulatory factor (IRF), also called iron responsive element-binding protein (IRE-BP), is a cytoplasmic RNA-binding protein which regulates post-transcriptionally transferrin receptor mRNA stability and ferritin mRNA translation. By using the polymerase chain reaction (PCR) and the sequence published by Rouault et al. (1990) a probe was derived which permitted the isolation of three human IRF cDNA clones. Hybridization to genomic DNA and mRNA, as well as sequencing data indicated a single copy gene of about 40 kb specifying a 4.0 kb mRNA that translates into a protein of 98,400 dalton. By in vitro transcription of a assembled IRF cDNA coupled to in vitro translation in a wheat germ extract, we obtained full sized IRF that bound specifically to a human ferritin IRE. In vitro translated IRF retained sensitivity to sulfhydryl oxidation by diamide and could be reactivated by beta-mercaptoethanol in the same way as native placental IRF. An IRF deletion mutant shortened by 132 amino acids at the COOH-terminus was no longer able to bind to an IRE, indicating that this region of the protein plays a role in RNA recognition. Placental IRF has previously been shown to migrate as a doublet on SDS-polyacrylamide gels. After V8 protease digestion the heterogeneity was located in a 65/70 kDa NH2-terminal doublet. The liberated 31 kDa COOH-terminal polypeptide was found to be homogeneous by amino acid sequencing supporting the conclusion of a single IRF gene.
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PMID:Expression of active iron regulatory factor from a full-length human cDNA by in vitro transcription/translation. 173 1

Iron overload was produced in Wistar rats by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe(3+)-NTA) for one to six months. Pancreatic tissues from these iron-overloaded rats and untreated controls were examined for insulin (for B cells), glucagon (for A cells), transferrin receptor (TfR), transferrin (Tf) and ferritin (Ft) using immunohistochemical methods, and for iron by histochemical Berlin blue staining. In the islets of iron-overloaded rats, increased Ft staining appeared prior to deposition of Berlin blue-stainable iron, and the staining intensity of Ft and iron was stronger in B cells than in A cells. In the islets of untreated control rats, the staining intensity of TfR was stronger in B cells than in A cells. TfR staining of the islets was weaker in iron-overloaded rats than in the controls. These findings suggest that 1) iron uptake by islet cells in vivo is regulated and mediated by TfR, 2) intracytoplasmic Ft transforms into stainable iron in iron-overloaded rats, and 3) predominance of TfR expression in B cells may result in selective deposition of iron and predispose B cells to damage and diabetes mellitus in iron-overloaded rats.
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PMID:Transferrin receptors and selective iron deposition in pancreatic B cells of iron-overloaded rats. 177 64

Iron stimulates ferritin synthesis in whole cells and animals, by increasing the entry of ferritin mRNA into polyribosomes. Dissection of the regulation at the molecular level has identified a 28-nucleotide, conserved, regulatory sequence (IRE = iron regulatory element) in the 5' non-coding region of ferritin mRNAs, plus trans-acting factor(s), one of which is a 90-kDa protein. The site of iron action is not entirely characterized but may involve heme; sequences in the 3' non-coding region of ferritin mRNA can modulate regulation. Ferritin mRNA is the first eukaryotic mRNA for which a conserved regulatory sequence and regulator protein have been identified. The same RNA-protein motif is used, through iron-dependent degradation of transferrin receptor mRNA, to decrease synthesis of the receptor and cellular iron uptake. The regulatory structure of the transferrin receptor mRNA is composed, in part, of five copies of the IRE in the 3' non-coding region. IRE structure, probed by cleavage with RNases T1, V1, 1,10-phenanthroline-Cu or modification with dimethyl sulfate, is a hairpin loop with conformational variations dependent on magnesium; a base-paired region flanking the IRE is also structurally sensitive to magnesium. Similar results were obtained with a synthetic 55-mer containing the IRE and with a full-length in vitro transcript with a G----A substitution in the loop.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ferritin mRNA probed, near the iron regulatory region, with protein and chemical (1,10-phenanthroline-Cu) nucleases. A possible role for base-paired flanking regions. 185 88

The intracellular iron level exerts a negative feedback on transferrin receptor (TfR) expression in cells requiring iron for their proliferation, in contrast to the positive feedback observed in monocytes-macrophages. It has been suggested recently that modulation of TfR and ferritin synthesis by iron is mediated through a cytoplasmic protein(s) (iron regulatory element-binding protein(s) (IRE-BP)), which interacts with ferritin and TfR mRNA at the level of hairpin structures (IRE), thus leading to inhibition of transferrin mRNA degradation and repression of ferritin mRNA translation. In the present study we have evaluated in parallel the level of TfR expression, ferritin, and IRE-BP in cultures of: (i) circulating human lymphocytes stimulated to proliferate by phytohemagglutinin (PHA) and (ii) circulating human monocytes maturing in vitro to macrophages. The cells were grown in either standard or iron-supplemented culture. TfR and ferritin expression was evaluated at both the protein and mRNA level. IRE-BP activity was measured by gel retardation assay in the absence or presence of beta-mercaptoethanol (spontaneous or total IRE-BP activity, respectively). Spontaneous IRE-BP activity, already present at low level in quiescent T lymphocytes, shows a gradual and marked increase in PHA-stimulated T cells from day 1 of culture onward. This increase is directly and strictly correlated with the initiation and gradual rise of TfR expression, which is in turn associated with a decrease of ferritin content. Both the rise of TfR and spontaneous IRE-BP activity are completely inhibited in iron-supplemented T cell cultures. In contrast, the total IRE-BP level is similar in both quiescent and PHA-stimulated lymphocytes, grown in cultures supplemented or not with iron salts. Monocytes maturing in vitro to macrophages show a sharp increase of spontaneous and, to a lesser extent, total IRE-BP; the addition of iron moderately stimulates the spontaneous IRE-BP activity but not the total one. Here again, the rise of spontaneous IRE-BP from very low to high activity is strictly related to the parallel increase of TfR expression and, suprisingly, also with a very pronounced rise of ferritin expression observed at both the mRNA and protein level. It is noteworthy the effect of beta-mercaptoethanol is cell specific, i.e. the ratio of total versus spontaneous IRE-BP activity is different in activated lymphocytes and maturing monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages. 185 22

To assess whether an abnormality in transferrin receptor expression or regulation could represent an underlying metabolic defect in the reticuloendothelial (RE) system in hemochromatosis, monocytes were analyzed for the expression of the transferrin receptor using a monoclonal antibody (Act II) to the transferrin receptor (CD71) and flow cytometric analysis. Hemochromatosis patients (n = 14), and normal volunteers with no clinical evidence of iron overload (n = 14) were studied. A significant inverse relationship was observed for the relationship between the expression of transferrin receptor on monocytes and log(hepatic iron concentration) in hemochromatosis patients (r = -0.59, P less than .02) and also for the relationship between the expression of transferrin receptor and log(serum ferritin) in normal volunteers (r = -0.90, P less than .001). There was no significant difference in the mean expression of monocyte transferrin receptor between hemochromatosis patients and normal volunteers. However, the expression of the transferrin receptor in hemochromatosis patients was disproportionately higher than would be predicted from the relationship between serum ferritin and transferrin receptor expression in normal volunteers. The inverse relationship of the monocyte transferrin receptor relative to body iron stores in hemochromatosis is consistent with observations in other tissues, and suggests that non-transferrin iron metabolism, including ferritin, requires further investigation in the RE cell in hemochromatosis.
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PMID:Expression of transferrin receptors on monocytes in hemochromatosis. 185 81

The present study was undertaken to examine the production of soluble transferrin receptor by K562 erythroleukaemia cells under controlled experimental conditions. The concentrations of soluble and cellular transferrin receptor were measured by immunoassay employing monoclonal antibodies. Cellular ferritin was also measured as an index of iron supply. With incubation up to 48 h there was a progressive increase in the concentration of soluble transferrin receptor. Manipulating iron supply by adding iron chelators or diferric transferrin to the incubation medium produced marked alterations in cellular receptor and ferritin content. Under all such conditions examined, the relationship between soluble and cellular receptor remained highly constant. These findings support clinical studies of serum receptor suggesting that over a broad spectrum of haematological disorders there is a fixed relationship between serum receptor and tissue receptor mass.
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PMID:Production of soluble transferrin receptor by K562 erythroleukaemia cells. 187 29

Measurements of peripheral blood lymphocyte surface transferrin receptor using flow cytometry show that phytohaemagglutinin (PHA) stimulation causes a marked increase in both the number of cells bearing receptors and the absolute number of receptors. This increase is accompanied by the interleukin-2 receptor and there is a progressive increase of cells in the S phase of their cycle. Furthermore, ferritin synthesis in proliferating cells, as determined by immunoprecipitation techniques, increases significantly compared to non-stimulated cells. Intracellular concentrations of both spleen-type and heart-type ferritin are also increased with a preferentially high proportion of heart-type ferritin. These results suggest that expression of transferrin receptor and synthesis of ferritin is regulated by a complex mechanism. Cellular proliferative activity increases the expression of transferrin receptor and could modulate the biosynthesis of intracellular ferritin that is normally controlled by iron. These two processes do not appear to be linked.
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PMID:Expression of cell surface transferrin receptor and intracellular ferritin after in vitro stimulation of peripheral blood T lymphocytes. 188 82

Iron-responsive elements (IREs) are regulatory RNA elements which serve as specific binding sites for the IRE-binding protein (IRE-BP). Interaction between IREs and IRE-BP induces repression of ferritin mRNA translation and transferrin receptor mRNA stabilization. We describe the identification of extensive amino acid sequence homology between IRE-BP and two known isomerases, aconitase and isopropylmalate (IPM) isomerase. We discuss the implications of this observation with regard to structure/function relationships of IRE-BP. The structural conservation between a regulatory RNA-binding protein and two enzymes involved in intermediary metabolism provides a surprising example of the functional flexibility in biological structures.
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PMID:Homology between IRE-BP, a regulatory RNA-binding protein, aconitase, and isopropylmalate isomerase. 190 2

Turnover of the full-length human transferrin receptor (TfR) mRNA is regulated by iron, and this regulation is mediated by the transcript's 3' untranslated region. Alterations in the sequence of the TfR mRNA regulatory region have been identified that render the mRNA unregulated by iron and intrinsically unstable. When cells expressing this unstable mRNA are treated with inhibitors of protein synthesis (cycloheximide or puromycin), the steady-state level of the encoded human TfR mRNA is increased due to a stabilization of the transcript. A similar set of observations has been made using a chimeric mRNA in which the rapid turnover determinant of the TfR mRNA is replaced by the (A+U)-rich region from the 3' untranslated region of c-fos mRNA. To distinguish between a labile protein participant in the degradation of these mRNAs and a requirement for their translation per se, we introduced a ferritin iron-responsive element into the 5' untranslated region of each of these mRNAs. The presence of the 5' iron-responsive element allowed us to use iron availability to alter the translation of the mRNAs in question without global effects on cellular protein synthesis. Although specific translation of these mRNAs could be inhibited by iron chelation to a degree comparable to that seen with cycloheximide (approximately 95% inhibition), no effects on mRNA turnover were observed. These data support a model in which a trans-acting labile protein is necessary for the turnover of these mRNAs rather than there being a requirement for the translation of the mRNAs themselves.
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PMID:Translation and the stability of mRNAs encoding the transferrin receptor and c-fos. 190 29


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