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

We have investigated the effect of iron on the expression of transferrin receptors (TrfRs) and ferritin chains in cultures of human peripheral blood monocytes maturing to macrophages. Monocyte-macrophage maturation is associated with a gradual rise of Trf-binding capacity in the absence of cell proliferation. At all culture times, treatment with ferric ammonium citrate induces a dose-dependent rise of the Trf-binding level as compared with nontreated cells. Scatchard analysis revealed that this phenomenon is due to an increase in receptor number rather than an alteration in ligand-receptor affinity. Biosynthesis experiments indicated that the rise in number of TrfRs is due to an increase of receptor synthesis, which is associated with a sustained elevation of the TrfR RNA level. The up-regulation of TrfR synthesis is specific in that expression of other macrophage membrane proteins is not affected by iron addition. Conversely, addition of an iron chelator induced a slight decrease of TrfR synthesis. The expression of heavy and light ferritin chains at RNA and protein levels was markedly more elevated in cultured macrophages than in fresh monocytes, thus suggesting modulation of ferritin genes at transcriptional or post-transcriptional levels. Addition of iron salts to monocyte-macrophage cultures sharply stimulated ferritin synthesis but only slightly enhanced the level of ferritin RNA, thus indicating a modulation at the translational level. These results suggests that in cultured human monocytes-macrophages, iron up-regulates TrfR expression, thus in sharp contrast to the negative feedback reported in a variety of other cell types. These observations may shed light on the mechanism(s) of iron storage in tissue macrophages under normal conditions and possibly on the pathogenesis of diseases characterized by abnormal iron storage.
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PMID:Iron up-modulates the expression of transferrin receptors during monocyte-macrophage maturation. 247 88

In order to examine the control mechanism of ferritin (Fr) and transferrin (Tf) synthesis depending on intracellular iron levels, the rate of 14C-leucine incorporation into those proteins was investigated by cell culture of isolated hepatocytes obtained from iron deficient, iron injected and control rats. The effects of iron (ferric ammonium citrate: FeAc) and (diferric Tf: 2FeTf) or desferrioxamine (Dfo) in culture media were also examined. Serum iron, TIBC and Hb levels of iron deficient rats, which were fed an iron deficient diet for 2 and 4 weeks were significantly lower than the control. However serum iron and TIBC levels of iron injected rats which had received 30 and 45 mg iron as iron dextran 18 h before sacrifice were approximately ten times higher than the control group. The time course of 14C-leucine incorporation into Fr and Tf was investigated at the 60, 120 and 180 minutes stages of the culture. Fr synthesis was increased by the amounts of iron injected, whereas Tf synthesis showed a negative response to iron. The 14C activities in Fr and Tf detected from culture media were proportional to those in hepatocytes. The percentage of nonglycosylated Fr was 82.0-91.4% for total Fr in the culture media in every experiment, which was measured by the affinity of glycosylated Fr to Con A-Sepharose (Con A). This result suggested the leakage of cytosol Fr through the cell membrane instead of specific secretion of the sialyl protein. The efficiency of Fr and Tf synthesis was positively or negatively proportional to cellular iron contents respectively. And the curves of 14C-leucine incorporation into both proteins, calculated as the sum of those in hepatocytes and culture media intersected at the point between the 30 mg iron injected and control groups. The addition of FeAC or 2FeTf into the culture media had an indistinct effect on Fr and Tf synthesis, whereas there was a significant decrease for Fr and a slight increase for Tf formations in the Dfo supplement. These results showed the influence of cellular iron levels in Fr and Tf synthesis.
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PMID:[Regulation of ferritin and transferrin synthesis in hepatocytes depending on iron status of rats]. 258 67

Arylsulphatases A, B and C were found to be inhibited in liver and kidney tissues under lead acetate-treated conditions (both in vivo and in vitro) in rats. When lead acetate-treated animals (in vivo) were supplemented with ferric ammonium citrate (in vivo), a remarkable recovery was found in the activities of all arylsulphatases A, B and C whereas ferric ammonium citrate itself had no effect on the activities of arylsulphatases. When both the in vivo and in vitro lead acetate-treated arylsulphatases were supplemented with the purified ferritins (in vitro) it was observed that lead-induced inhibition of the activities of arylsulphatases was successfully reversed. It was also found that ferritins were able to bind a large quantity of lead. These results indicated that ferritins were directly involved for reactivation of arylsulphatases which were inhibited by lead. It was well established that a response to iron administration in rats was an immediate de novo stimulation of ferritin biosynthesis. Iron might therefore protect the enzymatic activities of arylsulphatases by enhancing the level of ferritin in liver and kidney tissues which is known to bind a large quantity of lead thereby ameliorating their toxic effects in the living system.
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PMID:Mode of action of iron on arylsulphatases under acute lead acetate treated conditions in rats. 277 25

A hybridoma cell line that secretes monoclonal antibody, MAb-ER-Br-1-15-4-18 is established. The MAb is highly specific for estrogen receptor (ER) from human breast tumor cells. In order to raise the antibody, the ER was first isolated from human breast tumor. Mice were immunized with the partially purified ER and the fusion of the spleen cells from the mouse, showing the highest serum titer, with the cells of the NS-1 mouse myeloma line, produced hybrid cells which continuously secreted antibodies specific for ER. Three of the hybridoma cultures which tested strongly positive were cloned using limiting dilution method and one of the cell lines was selected for further study. The recovery of the MAb from the cell culture was done by ammonium sulfate precipitation followed by dialysis and then hydroxylapatite liquid chromatography using linear gradients. The purity of the antibody was checked by polyacrylamide gel electrophoresis. The MAb was isotyped and found to be IgG1. When checked against other antigens the MAb showed a minimal cross-reactivity to ER from rabbit uterus and none to ovalbumin or rat liver ferritin. Further experiments showed that the MAb recognized the ER bound to the hormone and ER in the nucleus of breast tumor cells.
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PMID:Production and characterization of a monoclonal antibody to partially purified estrogen receptor from human breast tumor. 292 8

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

Resting human T-lymphocytes show an elevated intracellular concentration of ferritin, whereas transferrin receptors are not detectable. Stimulation by phytohemagglutinin markedly lowers their ferritin content, while inducing the synthesis of transferrin receptors. Addition of iron salts (ferric ammonium citrate) in activated T-lymphocyte cultures causes a marked enhancement of both [3H]uridine and [3H]thymidine incorporation. Nevertheless, it also induces a concentration-dependent decrease in transferrin receptor synthesis, associated with a marked rise of ferritin production. Hemin treatment exerts the same effects. Addition of picolinic acid in phytohemagglutinin-stimulated cultures causes a decrease of [3H]thymidine incorporation, whereas transferrin expression is markedly enhanced. The action of iron salts and chelators is specific for transferrin receptors, since the expression of other membrane markers of activated human T-lymphocytes (interleukin-2 receptor, insulin receptor, and HLA-DR antigen) is not modified by treatment with iron or picolinic acid. These observations suggest that expression of transferrin receptors in activated T-lymphocytes is specifically modulated by their intracellular iron level, rather than their proliferative rate. Addition of picolinic acid to resting T-lymphocytes in the absence of mitogen induces a marked decrease of their ferritin content, but not the appearance of transferrin receptors. On the basis of these results, we suggest a three-step model: (a) in resting T-lymphocytes, the gene for transferrin receptor is apparently "closed," in that it is not expressed under both normal conditions and following iron deprivation. (b) After mitogen stimulus, T-lymphocytes are reprogrammed into cell cycle progression, which necessarily entails synthesis of transferrin receptors (c) Expression of these receptors is modulated by the intracellular iron level, rather than the rate of proliferation per se.
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PMID:Expression of transferrin receptors in phytohemagglutinin-stimulated human T-lymphocytes. Evidence for a three-step model. 300 77

Vanadium associates with serum transferrin of rats administered vanadyl(IV) sulfate or ammonium metavanadate(V) by gastric intubation. Low molecular weight species account for only 3% of the vanadium present in plasma. The element distributes between the two major isotransferrins in proportion to their concentrations. Rat apotransferrin binds both vanadium(IV) and vanadium(V), forming 2:1 metal-protein complexes in both instances. Although the two isotransferrins apparently differ in their physiological properties, they exhibit identical vanadyl(IV) (VO2+) EPR spectra, indicating identical or very similar metal binding sites for both proteins. In contrast to other transferrins, the two sites of the rat protein are spectroscopically indistinguishable and exhibit a VO2+ EPR spectrum similar to that of the C-terminal metal binding site of human serum transferrin. VO2+ EPR signals are observed with liver, spleen, and kidney tissue samples from animals maintained on a vanadium-supplemented diet. These signals arise from a specific intracellular VO2+ complex with the iron storage protein ferritin.
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PMID:Vanadium complexes of transferrin and ferritin in the rat. 302 Dec 34

Mouse and rabbit ferritin mRNAs translate very poorly in rabbit reticulocyte lysates relative to most other mRNAs. This translational deficiency is not seen in wheat germ lysates, suggesting the presence of an inhibitor in reticulocyte lysate that is specific for ferritin mRNA. A specific repressor of ferritin mRNA translation has been partially purified from rabbit reticulocytes by differential ultracentrifugation, ammonium sulfate fractionation, and chromatography on phosphocellulose, DEAE-cellulose, and Sephacryl S-300. The elution profile from the latter suggests an aggregate molecular mass of approximately 180 kDa for the repressor. The inhibitory activity of this repressor against native ferritin mRNA can be relieved by adding in vitro transcripts of ferritin light-chain RNAs that contain the first 92 nucleotides of the 5' untranslated region. No other sequences appear to be necessary for this effect.
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PMID:Translational repression in eukaryotes: partial purification and characterization of a repressor of ferritin mRNA translation. 320 Aug 35

Mouse (MEL) and human (K-562) erythroleukemia cell lines can be induced to undergo erythroid differentiation, including hemoglobin (Hb) synthesis, by extra cellular hemin. In order to study the effect of extracellular hemin on intracellular ferritin and Hb content, we have used Mossabauer spectroscopy to measure the amount of 57Fe incorporated into ferritin or Hb and a fluorescent enzyme-linked immunosorbent assay (ELISA) to measure the ferritin protein content. When K-562 cells were cultured in the presence of a 57Fe source either as transferrin or citrate, in the absence of a differentiation inducer, all the intracellular 57Fe was detected in ferritin. When the cells were cultured in the presence of 57Fe-hemin, 57Fe was found in both ferritin and Hb. 57Fe in ferritin increased rapidly, and after 2 days it reached a plateau at 5 X 10(-14) g/cell. 57Fe in Hb increased linearly with time and reached the same value after 12 days. Addition of other iron sources such as iron-saturated transferrin, iron citrate, or iron ammonium citrate caused a much lower increase in ferritin protein content as compared to hemin. When K-562 cells were induced by 57Fe-hemin in the presence of 56Fe-transferrin, 57Fe was found to be incorporated in equal amounts into both ferritin and Hb. However, when the cells were induced by 56Fe-hemin in the presence of 57Fe-transferrin, 57Fe was incorporated only into ferritin, but not into Hb, which contained 56Fe iron. These results indicate that in K-562 cells, when hemin is present in the culture medium it is preferentially incorporated into Hb, regardless of the availability of other extra- or intracellular iron sources such as transferrin or ferritin. In MEL cells induced to differentiate by dimethylsulfoxide (DMSO) a different pattern of iron incorporation was observed; 57Fe from both transferrin and hemin was found to incorporate in ferritin as well as in Hb.
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PMID:Effect of extracellular hemin on hemoglobin and ferritin content of erythroleukemia cells. 347 Feb 97

Acute administration of iron to rats has been previously shown to induce liver ferritin synthesis by increasing the translation of inactive cytoplasmic ferritin mRNAs for both heavy (H) and light (L) subunits by mobilizing them onto polyribosomes. In this report rat hepatoma cells in culture are used to explore the relationship of this response to intracellular iron levels. After adding iron as ferric ammonium citrate to the medium, latent ferritin H- and L-mRNAs were extensively transferred to polyribosomes, accompanied by increased uptake of [35S]methionine into ferritin protein. Because total cellular levels of L- and H-mRNA were not significantly changed by exposure to iron, the increased ferritin mRNAs on polyribosomes most probably come from an inactive cytoplasmic pool, consistent with the inability of actinomycin-D and of cordycepin to inhibit iron-induced ferritin synthesis. When deferoxamine mesylate, an intracellular iron chelator, was added after the addition of iron to the medium, ferritin mRNA on the polyribosomes was reduced, while the free messenger pool increased, and ferritin synthesis diminished. In contrast, the extracellular iron chelator diethylenetriaminepentaacetic acid failed to inhibit the induction of ferritin protein synthesis. Addition of iron in the form of hemin also caused translocation of mRNA to polyribosomes, a response that could be similarly quenched by deferoxamine. Because hemin does not release chelatable iron extracellularly, we conclude that the level of chelatable iron within the cell has a regulatory role in ferritin synthesis through redistribution of the messenger RNAs between the free mRNA pool and the polyribosomes.
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PMID:Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells. 347 Jul 92


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