UNIPROT:P02794 - FACTA Search

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

Patients on a moderate red cell transfusion programme have iron overload where the concentrations of the serum ferritin were inappropriate to increases in the transfusion load as a result of limitations of apoferritin synthesis and conversion of ferritin into haemosiderin. This study confirms the limitations for the use of estimations of the serum ferritin to evaluate the iron status in patients with expected high overload as would be seen in patients on many years of maintenance red cell transfusions in the absence of iron chelation therapy. Poor compliance, inadequate dosage of Desferal (deferoxamine), and the late initiation of iron chelation therapy were factors that were considered in the patients with failure of response to iron chelation.
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PMID:Serum ferritin concentrations in transfusion dependent beta-thalassaemia. 800 83

The identification of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as dopaminergic neurotoxins that can induce parkinsonism in humans and animals has contributed to a better understanding of Parkinson's disease (PD). Although the involvement of similar neurotoxins has been implicated in PD, the etiology of the disease remains obscure. However, the recently described pathology of PD supports the view for a state of oxidative stress in the substantia nigra (SN), resulting as a consequence of the selective accumulation of iron in SN zona compacta and within the melanized dopamine neurons. Whether iron is directly involved cannot be ascertained. Nevertheless, the biochemical changes due to oxidative stress resulting from tissue iron overload (siderosis) are similar to those now being identified in parkinsonian SN. These include the reduction of mitochondrial electron transport, complex I and III activities, glutathione peroxidase activity, glutathione (GSH) ascorbate, calcium-binding protein, and superoxide dismutase and increase of basal lipid peroxidation and deposition of iron. The participation of iron-induced oxygen free radicals in the process of nigrostriatal dopamine neuron degeneration is strengthened by recent studies in which the neurotoxicity of 6-OHDA has been linked to the release of iron from its binding sites in ferritin. This is further supported by experiments with the prototype iron chelator, desferrioxamine (Desferal), a free-radical inhibitor, which protects against 6-OHDA-induced lesions in the rat. Indeed, intranigral iron injection in rats produces a selective lesioning of dopamine neurons, resulting in a behavioral and biochemical parkinsonism.
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PMID:The possible role of iron in the etiopathology of Parkinson's disease. 841 92

We have recently identified ferritin as a cellular protein particle whose synthesis is stimulated in mouse or human cells infected by the picornavirus Mengo. Immunoprecipitation of the particle from infected murine L929 cells showed a 4- and 6-fold increase in the intracellular concentrations of H and L apoferritin subunits, respectively. This differential expression altered the H/L subunit ratio from 3.0 in uninfected cells to 2.2 in Mengo virus-infected cells. The induction is not due to an increase in transcription of the apoferritin L and H genes, nor is it due to an increase in stability of the apoferritin mRNAs. At the level of translation, the iron regulatory protein (IRP) remained intact, with similar amounts being detected in uninfected and infected cells. The Mengo virus RNA genome does not compete with the iron regulatory element (IRE) for the binding of IRP, and sequence analysis confirmed that there are no IREs in the virus RNA. The IRE binding activity of IRP in infected cells decreased approximately 30% compared with uninfected cells. The decrease in binding activity could be overcome by the addition of Desferal (deferoxamine mesylate; CIBA) an intracellular iron chelator, which suggests that virus infection causes an increase in intracellular free iron. Electron paramagnetic resonance (EPR) studies have confirmed the increase in free iron in Mengo virus infected cells. The permeability of cells for iron does not change in virus infected cells, suggesting that the induction of ferritin by Mengo virus is due to a change in the form of intracellular iron from a bound to a free state.
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PMID:Induction of ferritin synthesis in cells infected with Mengo virus. 862 69

Iron regulatory proteins (IRPs) are RNA-binding proteins that post-transcriptionally regulate synthesis of iron uptake (transferrin receptor) and storage (ferritin) proteins. Our previous work demonstrating that IRP1 is phosphorylated by protein kinase C supported the hypothesis that factors in addition to iron modulate IRP function. We have investigated changes in activity and expression of both IRP1 and IRP2 during phorbol 12-myristate 13-acetate (PMA)-induced differentiation of HL-60 cells. In contrast to IRP1, IRP2 was highly phosphorylated in untreated cells. PMA stimulated phosphorylation of IRP1 and IRP2 by at least 2-3-fold without affecting incorporation of [35S]methionine into the proteins. IRP1 and IRP2 isolated from PMA-treated cells displayed different phosphopeptides. Phosphorylation of IRPs was associated with a 2-fold increase in high affinity RNA binding activity without altering KD, and this was accompanied by a 50% increase in transferrin receptor mRNA abundance. PMA acted on a latent pool of binding activity that is present in a nonaconitase oxidized form and is largely composed of a stable but inactive species of IRP2. Desferal and hemin modulated iron-responsive element binding activity in HL-60 cells without affecting the phosphorylation state of IRP1. Hemin appeared to reduce the abundance of phosphorylated IRP2. Thus, multiple factors affect the function of both IRPs and indicate that extracellular agents may program changes in cellular iron metabolism by altering the phosphorylation state of these regulatory RNA-binding proteins.
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PMID:Phosphorylation and activation of both iron regulatory proteins 1 and 2 in HL-60 cells. 863 54

The objective of this study was to determine the prevalence and possible pathogenesis of scoliosis in beta-thalassemia in our country, and to compare its characteristics to those of patients with idiopathic scoliosis from the same geographic area. Twenty-four [13 male and 11 female thalassemic patients aged 16 +/- 7 years (range 7-32 years)] of 115 examined patients with beta-thalassemia showed scoliosis of 14 degrees +/- 11 (range 10-65 degrees) radiologically. The prevalence of scoliosis in the thalassemic population was 21% in this series, whereas the overall prevalence of scoliosis in the general Greek population was 6% (Smyrnis PN, Valavanis J, Alexopoulos A, Siderakis G, Giannestras NJ: School screening for scoliosis in Athens, J Bone Joint Surg 61B:215-217, 1979). The scoliosis prevalence in the general population was significantly higher in the females (5%) than in the males (1%), whereas no difference in prevalence was found between the two sexes in the thalassemic population. The most common curve pattern in thalassemia was the left lumbar (38%) followed by the right lumbar (21%), whereas in patients with idiopathic scoliosis the left thoracolumbar most commonly appeared (25%) followed by the left lumbar (14%). No patient with thalassemia showed radiographic signs of congenital spinal deformities and spinal fractures, whereas all patients showed a significant retardation of their skeletal maturation. The age of the thalassemic patients with scoliosis was significantly (p = 0.0003) higher than in patients without scoliosis. The hematocrit of the thalassemic patients with scoliosis was significantly (p = 0.0012) lower than in those without scoliosis, whereas the rate of transfusions was not correlated with the magnitude of the scoliosis. The level of ferritin was significantly (p = 0.025) higher in the thalassemic patients with scoliosis than in those without scoliosis. The duration of Desferal treatment was significantly (p = 0.0357) longer in thalassemic patients with scoliosis when compared with those without scoliosis. Thus, the prevalence, curve pattern, and etiology of scoliosis in beta-thalassemia differ from those of idiopathic scoliosis, indicating that the spinal deformities in thalassemia represent a distinct type of scoliosis.
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PMID:Prevalence of scoliosis in beta-thalassemia. 879 87

Mouse erythroleukemia (MEL) cells transformed by Friend virus and induced to undergo erythroid differentiation by treatment with hexamethylenebisacetamide (HMBA) increase erythroid specific 5-aminolevulinate synthase (ALAS-E) mRNA levels by 4-15-fold and decrease "housekeeping" 5-aminolevulinate synthase (ALAS-N) mRNA levels by 1.2-1.4-fold. Iron affects translation of (ALAS-E) mRNA but nothing is known about its effect at the pretranslational level of the expression of (ALAS-E) mRNA. The aim of this study was to examine the effect of iron on the synthesis of (ALAS-E) mRNA and (ALAS-N) mRNA. This effect was compared with the effect of iron on the iron on the synthesis of H-ferritin and transferrin receptor mRNAs. Incubation of uninduced or induced MEL cells with iron chelator pyridoxal isonicotinoyl hydrazone (PIH) or desferrioxamine (Desferal) and 3H-uridine decreased the level of the 3H-labeled (ALAS-E) mRNA. The treatment with either diferric transferrin or Fe-PIH increased the level of the 3H-labeled (ALAS-E) mRNA. The opposite effect was observed on the level of the 3H-labeled (ALAS-N) mRNA. These findings indicate that iron might play its role also at the pretranslational level of the expression of ALAS-E or in the stability of (ALAS-E) mRNA.
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PMID:The role of iron supply in the regulation of 5-aminolevulinate synthase mRNA levels in murine erythroleukemia cells. 884 57

Ferritin is the main intracellular iron storage protein. Ferritin iron may be released by many reducing agents including ascorbate. In this work we report ferritin to catalyze the oxidation of ascorbate. The kinetics of this process were studied in detail in phosphate buffer (pH 7.40), at 37 degrees C by using the Clark electrode technique and ESR. The catalytic effect of ferritin manifested itself as the increase both in the rate of oxygen uptake and steady-state concentration of the ascorbate radical. The ferritin catalytic activity was found to be modified by iron chelators, EDTA. Desferal (DFO) as well as by ferrozine (FRZ) which is widely used in kinetic studies on ferritin iron release thanks to the formation of a coloured complex with Fe(II). While EDTA promotes the catalytic action of ferritin, DFO and FRZ diminished it. From the comparison of the kinetics of ascorbate oxidation obtained in the current work and data on the kinetics of ferritin iron release reported by Boyer and McCleary ((1987) Free Rad. Biol. Med. 3, 389-395), we conclude that iron bound to ferritin rather than the iron released is likely responsible for ferritin catalytic action. In addition, it has been concluded that the use of FRZ as an analytical reagent in kinetic studies of reductive ferritin iron release requires taking into account the competitive character of the formation of the Fe(II)-FRZ complex.
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PMID:Iron bound to ferritin catalyzes ascorbate oxidation: effects of chelating agents. 913 40

Utilization of mRNAs containing iron-responsive elements (IREs) is modulated by iron-regulated RNA-binding proteins (iron regulatory proteins). We examine herein whether iron differentially affects translation of ferritin and mitochondrial aconitase (m-Acon) mRNAs because they contain a similar but not identical IRE in their 5'-untranslated regions. First, we demonstrate that m-Acon synthesis is iron-regulated in mammalian cells. In HL-60 cells, hemin (an iron source) stimulated m-Acon synthesis 3-fold after 4 h compared with cells treated with an iron chelator (Desferal). Furthermore, hemin stimulated m-Acon synthesis 2-4-fold in several cell lines. Second, we show that iron modulates the polysomal association of m-Acon mRNA. We observed m-Acon mRNA in both ribonucleoprotein and polyribosomal fractions of HL-60 cells. Hemin significantly increased the polyribosomal association and decreased the ribonucleoprotein abundance of m-Acon mRNA in HL-60 cells. Third, our results indicate that iron differentially regulates translation of m-Acon and ferritin mRNAs. A dose response to hemin in HL-60 cells elicited a 2-2.4-fold increase in m-Acon synthesis within 5 h compared with untreated cells, whereas ferritin synthesis was stimulated 20-100-fold. We conclude that iron modulates m-Acon synthesis at the translational level and that iron regulatory proteins appear to differentially affect translation of IRE-containing mRNAs.
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PMID:Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization. 945 6

The effect of protoporphyrin IX (hemin without iron) on the expression of transferrin receptor and ferritin was investigated in Friend leukemia cells. Cells treated with protoporphyrin IX exhibit enhanced transferrin-receptor expression and markedly reduced ferritin synthesis. Stimulation of transferrin-receptor expression is observed at both the mRNA and protein level. The effect on ferritin synthesis is mediated by translational inhibition of the mRNA, which, in contrast, is transcriptionally stimulated by protoporphyrin IX treatment. The regulation of transferrin receptor and ferritin in response to iron perturbations has been studied extensively and is mediated by the binding of iron-regulatory proteins (IRP) to the iron-responsive elements (IRE) present in the 3' and 5' untranslated regions of the transferrin-receptor and ferritin mRNA, respectively. To elucidate the molecular mechanisms underlying the effects of protoporphyrin IX on ferritin and transferrin-receptor expression, the role of the IRE sequence was investigated both in vivo by transfection experiments, with a construct containing the coding region for the chloramphenicol acetyltransferase (CAT) reporter gene under the translational control of the ferritin IRE, and in vitro by RNA band-shift assays. Whereas, examination of IRP binding to the IRE by in vitro assays suggests an apparent inactivation of IRP by protoporphyrin IX treatment, CAT assays indicate that protoporphyrin IX is able to induce in vivo a translational inhibition similar to that obtained by treatment with the iron chelator Desferal. This observation raises the possibility of different effects on the IRP activity exerted by porphyrin treatment in intact tissue-culture cells and in vitro. We conclude that translation of ferritin mRNA and degradation of transferrin-receptor mRNA are inhibited in intact tissue-culture cells by protoporphyrin IX through a mechanism similar to that exerted by iron chelation, thus involving depletion of the intracellular iron pool. These results can improve the understanding of the regulation of ferritin gene expression in some pathological conditions associated with disturbed heme synthesis.
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PMID:Regulation of expression of ferritin H-chain and transferrin receptor by protoporphyrin IX. 946

In most eukaryotic cells, synthesis of the iron storage protein, ferritin is regulated by iron levels and redox conditions. Proper iron storage is important to protect against damaging iron-catalysed free radical reactions. Although iron-catalysed reactions are believed to contribute to oxidative damage and cataractogenesis, little is known about iron storage in the lens. In this study, ferritin concentration was measured in cultured canine lens epithelial cells. Baseline ferritin concentration ranged from 76-163 ng (mg protein)-1; cells cultured in low-iron media had significantly lower ferritin levels than cells cultured in iron-supplemented media. Addition of a large excess of iron as hemin resulted in an eight-fold increase in ferritin concentration. The iron chelator, Desferal, significantly decreased ferritin concentration. The reducing agent dithiothreitol decreased the hemin-induced increase in ferritin levels, but not baseline levels. In contrast, ascorbic acid induced a large increase in ferritin content. Other studies have shown that induction of ferritin synthesis can protect against oxidative damage. Regulation of ferritin levels may represent a mechanism by which the lens epithelium is protected from oxidative damage. In vivo, epithelial cells are normally exposed to much lower iron concentrations than the cultured lens epithelial cells in this study. However, in pathological circumstances, the iron content and redox state of the aqueous humor is dramatically altered and may affect the steady state levels of ferritin within the lens. This remains to be determined.
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PMID:Regulation of ferritin levels in cultured lens epithelial cells. 949 56

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