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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 succinylacetone (SA), a highly specific inhibitor of ALA-dehydratase and heme synthesis, on hemoglobin (Hb) production, transferrin receptor (TfR), and ferritin expression was analyzed in differentiating Friend leukemia cells (FLC). This compound exerted a pronounced inhibitory effect not only on heme and Hb synthesis, but also on all the remaining above-mentioned parameters. In particular, SA induced: (1) a reduction of the level of alpha-globin mRNA; (2) a decreased number of exposed TfR molecules, without modification of their affinity for the ligand; (3) a reduced level of TfR RNA, without significant change of TfR gene transcription rate; and (4) a lower ferritin content. The addition of exogenous hemin to differentiating FLC exerted opposite effects, and particularly induced an increase of both the number of TfRs and ferritin content. These findings suggest that in erythroid cells optimal heme synthesis is required to coordinately sustain globin chains synthesis and TfR/ferritin production; thus, the intracellular heme level may represent a key regulatory factor in the Hb synthesis pathway.
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PMID:Intracellular heme coordinately modulates globin chain synthesis, transferrin receptor number, and ferritin content in differentiating Friend erythroleukemia cells. 191 86

Serum levels of transferrin receptor and erythropoietin were determined in 2 patients with hereditary hemochromatosis undergoing phlebotomy therapy. The objective of the study was to determine changes in serum transferrin receptor and serum erythropoietin occurring during therapy, and to investigate if such changes could be useful to monitor the therapy. The study showed that serum transferrin receptor, and to a lesser extent serum erythropoietin, may be better parameters than serum ferritin as indicators of when phlebotomy should be discontinued. The most sensitive parameter, however, appeared to be the serum transferrin receptor/ferritin ratio.
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PMID:Variations in serum erythropoietin and transferrin receptor during phlebotomy therapy of hereditary hemochromatosis: a case report. 191 5

Measurements of circulating transferrin receptor provide a sensitive quantitative index of tissue iron deficiency in otherwise healthy subjects. This investigation was undertaken to examine the diagnostic utility of this new iron index in pregnancy. A battery of iron-related measurements, including serum transferrin receptor concentrations, was performed on 176 women in third-trimester pregnancy who were attending a university prenatal clinic. The mean receptor concentration of 5.96 +/- 2.37 mg/L (+/- 1 SD) did not differ significantly from concentrations in nonpregnant individuals and the frequency distributions were likewise comparable. Elevations in serum receptor greater than 8.5 mg/L occurred only in women with depleted iron stores defined by serum ferritin concentrations. Abnormal concentrations were found in 11 of 13 women with overt iron-deficiency anemia. Our findings indicate that serum receptor concentrations are not influenced by pregnancy per se and are a sensitive index of iron deficiency. By combining serum receptor and serum ferritin measurements, the entire spectrum of iron status in pregnancy can be assessed.
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PMID:Serum transferrin receptor for the detection of iron deficiency in pregnancy. 195 24

Although many studies have examined the regulation of transferrin, transferrin receptor and ferritin subunit gene expression in experimental systems, no molecular biological data in humans have been documented to date. In this study we simultaneously analyzed the hepatic content of transferrin, transferrin receptor and heavy and light ferritin subunit messenger RNAs in tissue samples obtained from subjects with normal iron balance and patients with primary or secondary iron overload. Steady-state levels of transferrin messenger RNA were not depressed by iron overload. On the contrary, they were increased (p less than 0.001) in patients with severe hepatic siderosis (liver iron content greater than 200 mumol/gm dry wt) as compared with the control group. This indicates that, as already suggested by our previous data in experimental siderosis, iron maintains the ability to induce transferrin gene activity even when cellular iron content is significantly increased. Transferrin receptor gene expression was found to respond in the same manner to any cause of iron-tissue load, regardless of the cause. In fact, a lower signal for transferrin receptor messenger RNA was consistently detected in iron-overloaded patients vs. control subjects, particularly in patients with thalassemia major and idiopathic hemochromatosis (p less than 0.001). Ferritin light-subunit messenger RNA accumulation was significantly increased in those patients with severe siderosis (idiopathic hemochromatosis and thalassemia major = liver iron between 200 and 600 mumol/gm dry wt). The fact that no significant change in hepatic ferritin heavy-subunit gene expression was detected in iron-loaded patients confirms preferential production of light-subunit--enriched ferritins in long-term iron overload.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of hepatic transferrin, transferrin receptor and ferritin genes in human siderosis. 195 58

Neonatal hemochromatosis (NH), a generally fatal disorder of infancy, is characterized by severe hepatic insufficiency of intrauterine onset and by marked organ iron loading. Its cause is unknown. It has been suggested that NH may represent an unusual manifestation of hereditary hemochromatosis (HH), which is human leukocyte antigen (HLA) linked. Evidence for major rearrangements or deletions at the HLA class I region and at three loci directly involved in iron metabolism (H- and L-apoferritin and the transferrin receptor [TfR]) was sought. The population studied included five probands with NH and 14 first-degree family members in a total of six kindreds. Also sought were HLA associations with NH by collating the results of HLA serotyping in these 19 persons and in 17 members of 7 additional kindreds in which NH has occurred, including 5 probands with NH and 12 first-degree family members. We found no evidence for major rearrangements or deletions in H- or L-apoferritin genes, in TfR genes, or within the HLA locus. We found no evidence for linkage of NH to HLA serotypes. We conclude that while NH and HH are similar in their patterns of iron loading, they are not genetically related.
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PMID:Neonatal hemochromatosis. Genetic analysis of transferrin-receptor, H-apoferritin, and L-apoferritin loci and of the human leukocyte antigen class I region. 197 98

We have studied transferrin receptor expression in MRC5 human fibroblasts in response to tumor necrosis factor-alpha (TNF, cachectin) or interleukin 1-alpha (IL-1). Treatment of exponentially growing MRC5 cells with these cytokines led to a 3-4-fold increase in transferrin receptor mRNA and a coordinate increase in transferrin receptor protein by 24 h. Under these conditions, stimulation of [3H]thymidine incorporation was minimal, suggesting that the induction of transferrin receptor by TNF and IL-1 is mediated by a growth-independent regulatory mechanism. A study of the time course of this response showed that cytokine-mediated increases in transferrin receptor mRNA and protein proceeded after a lag of 12-24 h. A simultaneous analysis of the effects of TNF and IL-1 on ferritin in MRC5 cells was also performed. Ferritin L mRNA levels were unchanged. However, induction of ferritin H mRNA was seen within 4 h, preceding the induction of the transferrin receptor. The synthesis of ferritin H (but not ferritin L) protein peaked at 8 h after TNF or IL-1 treatment, followed by a rapid decrease in both ferritin H and L protein synthesis. As ferritin H synthesis declined, levels of transferrin receptor protein increased, reaching a maximum by 24 h. These results suggest that the cytokine-dependent induction of ferritin H and subsequent increase in the transferrin receptor are related and possibly interdependent events. This study demonstrates that the complex role of TNF and IL-1 in iron homeostasis includes modulation of the transferrin receptor.
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PMID:Tumor necrosis factor-alpha and interleukin 1-alpha regulate transferrin receptor in human diploid fibroblasts. Relationship to the induction of ferritin heavy chain. 201 26

5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway. cDNA clones for the human erythroid ALAS isozyme were isolated from a fetal liver library. It can be deduced that the erythroid ALAS precursor protein has a molecular weight of 64.6 kd, and is similar in size to the previously isolated human housekeeping ALAS precursor of molecular weight 70.6 kd. The mature mitochondrial forms of the erythroid and housekeeping ALAS isozymes are predicted to have molecular weights of 59.5 kd and 64.6 kd, respectively. The two isozymes show little amino acid identity in their N-terminal signal sequences but have considerable sequence identity in the C-terminal two-thirds of their proteins. An analysis of the immediate promoter of the human erythroid ALAS gene revealed several putative erythroid-specific cis-acting elements including both a GATA-1 and an NF-E2 binding site. An iron-responsive element (IRE) motif has been identified in the 5'-untranslated region of the human erythroid ALAS mRNA, but is not present in the housekeeping ALAS mRNA. Gel retardation experiments established that this IRE motif formed a protein - RNA complex with cytosolic extracts from human K562 cells and this binding was strongly competed with IRE transcripts from ferritin or transferrin receptor mRNAs. A transcript of the ALAS IRE, mutated in the conserved loop of the IRE, did not readily form this protein - RNA complex. These results suggest that the IRE motif in the ALAS mRNA is functional and imply that translation of the mRNA is controlled by cellular iron availability during erythropoiesis.
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PMID:Human erythroid 5-aminolevulinate synthase: promoter analysis and identification of an iron-responsive element in the mRNA. 205 Jan 25

Iron-responsive elements (IREs) are regulatory RNA elements which are characterized by a phylogenetically defined sequence-structure motif. Their biological function is to provide a specific binding site for the IRE-binding protein (IRE-BP). Iron starvation of cells induces high affinity binding of the cytoplasmic IRE-BP to an IRE which has at least two different known biological consequences, repression of ferritin mRNA translation and stabilization of the transferrin receptor transcript. We report the identification of a novel, evolutionarily conserved IRE motif in the 5' UTR of murine and human erythroid-specific delta-aminolevulinic acid synthase (eALAS) mRNA which encodes the first, and possibly rate limiting, enzyme of the heme biosynthetic pathway. We demonstrate the function of the eALAS IRE as a specific binding site for the IRE-BP by gel retardation analyses and by in vitro translation experiments. In addition, we show that the 5' UTR of eALAS mRNA is sufficient to mediate iron-dependent translational regulation in vivo. These findings strongly suggest involvement of the IRE-IRE-BP system in the control of heme biosynthesis during erythroid differentiation.
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PMID:Identification of a novel iron-responsive element in murine and human erythroid delta-aminolevulinic acid synthase mRNA. 205 Jan 26

We describe a simple method for the affinity purification of specific RNA-binding proteins. DNA sequences corresponding to the protein-binding site of the RNA are subcloned into an in vitro transcription vector between the T7 viral promoter and a poly(A) track. A polyadenylated RNA transcript is bound to poly(U)-Sepharose and subsequently incubated with a cellular extract prepurified on heparin-agarose. Specifically adsorbed proteins are recovered in high yield and purity from the affinity matrix by high salt elution. Using this method we isolated the iron regulatory factor (IRF), a cytoplasmic protein which binds to specific palindromic elements in the 5' and 3' untranslated sequences of ferritin and transferrin receptor mRNA, respectively. Activation and binding of this regulatory factor correlates with increased transferrin receptor mRNA stability and inhibition of ferritin translation. The purified factor from human placenta migrates as a monomer in gel chromatography, but is present in equimolar amounts of two proteins with molecular weights of 95 and 100 kDa when analysed by SDS/PAGE. The two proteins are highly related as judged by the identity of their isoelectric points and their specificity to form RNA-protein complexes.
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PMID:A high yield affinity purification method for specific RNA-binding proteins: isolation of the iron regulatory factor from human placenta. 210 65

Ferritin is a ubiquitous iron-storage protein found in the cells of animals, plants, molds, and bacteria which it protects from toxic intracellular levels of iron. Ferritin stores iron within a hollow protein shell formed by subunits of two types, H and L. The 5' untranslated regions of the two subunit mRNAs contain an almost identical 28-nucleotide sequence which regulates translation by binding to a specific cell sap protein. When cell iron level is low, this repressor protein obstructs translation of stored ferritin mRNAs, whereas increased iron levels release this protein, thus permitting extensive ferritin subunit synthesis to respond rapidly. Similar motifs in the 3' untranslated region of transferrin receptor mRNA interact with this protein to regulate breakdown of the mRNA and thus change the receptor population. Finally, transcription of the H and L genes can be independently increased by iron and other factors. In the case of iron, synthesis of the L-mRNA is increased preferentially since ferritin shells with a preponderance of L-subunits store iron more efficiently. Thus regulation of ferritin synthesis at the translational and transcriptional levels and by transferrin receptor mRNA abundance at the level of breakdown provide a coordinated mechanism for protecting cells against the effects of excess iron.
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PMID:Iron regulation of ferritin gene expression. 212 93


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