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

Iron increases ferritin synthesis, targeting plant DNA and animal mRNA. The ferritin promoter in plants has not been identified, in contrast to the ferritin promoter and mRNA iron-responsive element (IRE) in animals. The soybean leaf, a natural tissue for ferritin expression, and DNA, with promoter deletions and luciferase or glucuronidase reporters, delivered with particle bombardment, were used to show that an 86-base pair fragment (iron regulatory element (FRE)) controlled iron-mediated derepression of the ferritin gene. Mutagenesis with linkers of random sequence detected two subdomains separated by 21 base pairs. FRE has no detectable homology to the animal IRE or to known promoters in DNA and bound a trans-acting factor in leaf cell extracts. FRE/factor binding was abrogated by increased tissue iron, in analogy to mRNA (IRE)/iron regulatory protein in animals. Maximum ferritin derepression was obtained with 50 microm iron citrate (1:10) or 500 microm iron citrate (1:1) but Fe-EDTA was ineffective, although the leaf iron concentration was increased; manganese, zinc, and copper had no effect. The basis for different responses in ferritin expression to different iron complexes, as well as the significance of using DNA but not mRNA as an iron regulatory target in plants, remain unknown.
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PMID:Identification and characterization of the iron regulatory element in the ferritin gene of a plant (soybean). 1074 12

Homologs of the ferric uptake regulator Fur and the iron storage protein ferritin play a central role in maintaining iron homeostasis in bacteria. The gastric pathogen Helicobacter pylori contains an iron-induced prokaryotic ferritin (Pfr) which has been shown to be involved in protection against metal toxicity and a Fur homolog which has not been functionally characterized in H. pylori. Analysis of an isogenic fur-negative mutant revealed that H. pylori Fur is required for metal-dependent regulation of ferritin. Iron starvation, as well as medium supplementation with nickel, zinc, copper, and manganese at nontoxic concentrations, repressed synthesis of ferritin in the wild-type strain but not in the H. pylori fur mutant. Fur-mediated regulation of ferritin synthesis occurs at the mRNA level. With respect to the regulation of ferritin expression, Fur behaves like a global metal-dependent repressor which is activated under iron-restricted conditions but also responds to different metals. Downregulation of ferritin expression by Fur might secure the availability of free iron in the cytoplasm, especially if iron is scarce or titrated out by other metals.
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PMID:Regulation of ferritin-mediated cytoplasmic iron storage by the ferric uptake regulator homolog (Fur) of Helicobacter pylori. 1102 12

An apparatus consisting of two pumps, a mixer, a ferritin reactor, and a spectrophotometer was constructed to study the ability to trap various heavy metal ions (M2+) and the dynamics of a reconstituted ferritin reactor in flowing seawater. Reconstituted pig spleen ferritin (PSFr) is assembled from apo-protein shell to form a reconstituted iron core. The main components of the PSFr are its core, which contains an Fe2+:Pi stoichiometry of 6.0 +/- 0.5, reconstituted from pig spleen apoferritin (apo PSF), Fe2+, inorganic phosphate (Pi), and O2 (0.6 atm). The Fe3+-Pi clusters within the PSFr core exhibit resistance to salt ranging from 1% to 6% NaCl. The ferritin reactor consists of PSFr and an oscillating bag. Using the reactor, M2+ ions such as Cd2+, Zn2+, Co2+, and Mn2+ are directly trapped by the ferritin. We found a 1:2 +/- 0.2 stoichiometry of the trapped M2+ to the released iron as measured by chemical analysis or atomic absorption spectrometry; nontransient elements such as Na+, K+, Ca2+, etc., were scarcely trapped by the reactor. This study provides basic conditions for establishing a ferritin reactor and a convenient means for monitoring the pollution of heavy metal ions in seawater.
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PMID:Construction of a ferritin reactor: an efficient means for trapping various heavy metal ions in flowing seawater. 1119 68

The Staphylococcus aureus genome encodes three ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of PerR, we inactivated the gene by allelic replacement using a kanamycin cassette, creating strain MJH001 (perR). PerR was found to control transcription of the genes encoding the oxidative stress resistance proteins catalase (KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin comigratory protein (Bcp), and thioredoxin reductase (TrxB). Furthermore, PerR regulates transcription of the genes encoding the iron storage proteins ferritin (Ftn) and the ferritin-like Dps homologue, MrgA. Transcription of perR was autoregulated, and PerR repressed transcription of the iron homeostasis regulator Fur, which is a positive regulator of catalase expression. PerR functions as a manganese-dependent, transcriptional repressor of the identified regulon. Elevated iron concentrations produced induction of the PerR regulon. PerR may act as a peroxide sensor, since addition of external hydrogen peroxide to 8325-4 (wild type) resulted in increased transcription of most of the PerR regulon, except for fur and perR itself. The PerR-regulated katA gene encodes the sole catalase of S. aureus, which is an important starvation survival determinant but is surprisingly not required for pathogenicity in a murine skin abscess model of infection. In contrast, PerR is not necessary for starvation survival but is required for full virulence (P < 0.005) in this model of infection. PerR of S. aureus may act as a redox sentinel protein during infection, analogous to the in vitro activities of OxyR and PerR of Escherichia coli and Bacillus subtilis, respectively. However, it differs in its response to the metal balance within the cell and has the added capability of regulating iron uptake and storage.
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PMID:PerR controls oxidative stress resistance and iron storage proteins and is required for virulence in Staphylococcus aureus. 1134 39

Deuterium kinetic isotope effects are widely used in chemical and biological research. Deuterium thermodynamic effects on the aqueous synthesis of inorganic materials, however, seem not to have been recognized. Here we report that the simple replacement of H(2)O with D(2)O in the synthesis of a solid-state manganese complex results in a new structurally and magnetically distinct phase. When iron oxides are synthesized, the relative amount of the mineral phases obtained in H(2)O vs D(2)O is different. The morphology and magnetic properties of the iron core of the iron storage protein ferritin are likewise different when mineralization is carried out in heavy water. The formation of extra inorganic solids, change in the ratio of two phases or alteration of a single phase morphology in D(2)O suggest that new inorganic and bioinorganic metal complexes might be obtained by using the thermodynamic isotope effect.
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PMID:Deuterium structural effects in inorganic and bioinorganic aggregates. 1190 96

The Staphylococcus aureus DtxR-like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal-depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR-dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci respectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR-regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)-regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co-ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.
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PMID:MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. 1202 79

Basal ganglia bilateral symmetric hyperintensity in T1-weighted sequences at magnetic resonance imaging (MRI) is recognized to be due to the presence of manganese deposits. This abnormal finding has been reported in occupational exposures, liver cirrhosis and total parenteral nutrition with unbalanced solutions. However, the same imaging is often observed "by chance" in brain MRIs of patients not belonging to these groups. In order to better understand which are the clinical conditions coexisting with such findings, we decided to study systematically patients which showed this kind of imaging, focusing on their manganese and iron status, as it is known that these two metals have similar properties and that iron-deficiency can competitively increase manganese absorption. The 20 patients studied underwent clinical evaluation and the following laboratory tests: whole blood iron and manganese, hemoglobin, plasma iron, transferrin and ferritin. The neuroradiologic evaluation was integrated by pallidal index calculation, in order to provide a semi-quantitative esteem of the hyperintensity. The patients could be classified into four subgroups: Parkinsonism, anemia, cirrhosis, central nervous system tumors. In 18 out of 20 cases, we found abnormalities in iron and/or manganese-related values. Particularly, iron-deficiency seems to be frequent among patients showing brain MRI abnormalities compatible with manganese deposits in basal ganglia. This observation suggests that iron-deficiency could be an important risk factor for manganese-induced neurotoxicity and should, therefore, be accurately considered and treated.
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PMID:T1-weighted hyperintensity in basal ganglia at brain magnetic resonance imaging: are different pathologies sharing a common mechanism? 1252 Jul 56

Anthracyclines are potent antitumor agents that cause cardiotoxicity at high cumulative doses. Because anthracycline cardiotoxicity is attributed to their ability to avidly bind iron (Fe), we examined the effect of anthracyclines on intracellular Fe trafficking in neoplastic cells and differentiated cardiomyocytes. In both cell types, incubation with doxorubicin (DOX) resulted in a significant (p < 0.004) accumulation of Fe in the storage protein, ferritin. Pulse-chase experiments using control cells demonstrated that within 6 h, the majority of (59)Fe donated from transferrin was incorporated into ferritin. Over longer incubation periods up to 18 to 24 h, (59)Fe was subsequently mobilized from ferritin into other compartments in control cells. However, anthracyclines inhibited ferritin-(59)Fe redistribution during the 18- to 24-h period, resulting in a significant (p < 0.0003) 3- to 5-fold accumulation of ferritin-(59)Fe compared with control cells. The increase in ferritin-(59)Fe after a 24-h incubation with DOX could not be correlated with increased ferritin expression, suggesting that (59)Fe accumulation occurred in pre-existing ferritin. In addition to DOX, other redox-cycling agents (i.e., menadione and paraquat) also increased ferritin-(59)Fe levels. Moreover, the intracellular superoxide scavenger, Mn(III) tetrakis(4-benzoic acid)-porphyrin complex, partially prevented the ability of DOX and menadione at inducing this effect. Hence, superoxide generation by these compounds could play a role in causing ferritin-(59)Fe accumulation. This study is the first to demonstrate the effect of anthracyclines at inhibiting Fe mobilization from ferritin, resulting in marked Fe accumulation within the molecule. This response may have consequences in terms of the cytotoxic effects of anthracyclines.
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PMID:Anthracyclines induce accumulation of iron in ferritin in myocardial and neoplastic cells: inhibition of the ferritin iron mobilization pathway. 1264 86

Manganese (Mn) may interfere with iron regulation by altering the binding of iron regulatory proteins (IRPs) to their response elements found on the mRNA encoding proteins critical to iron homeostasis. To explore this, the effects of 24-h in vitro manganese exposure (1, 10, 50, and 200 microM Mn) on: (i) total intracellular and labile iron concentrations; (ii) the cellular abundance of transferrin receptor (TfR), H- and L-ferritin, and mitochondrial aconitase proteins; and (iii) IRP binding to a [32P](-) labeled mRNA sequence of L-ferritin were evaluated in undifferentiated PC12 cells. In vitro manganese exposure altered the cellular abundance of TfR, H-/L-ferritin, and m-aconitase, resulting in an increase in labile iron. This latter effect led to a decrease in IRP binding activity at the lower (10 and 50 microM) manganese exposures. In contrast, 200 microM manganese exposure increased IRP binding, in spite of the significant increase in labile iron. These data indicate that at lower exposures, manganese directly interfered with IRP-dependent translational events, producing an increase in labile iron, which in turn signaled a decrease in IRP binding at 24 h. At higher exposures, the intracellular burden of manganese resulted in overt cytotoxicity and appeared to compromise the normal compensatory response to increased labile iron, producing increased IRP binding. We conclude that low to moderate manganese exposure interferes with cellular iron regulation, and thus may serve as a contributory mechanism underlying manganese neurotoxicity.
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PMID:Alterations in cellular IRP-dependent iron regulation by in vitro manganese exposure in undifferentiated PC12 cells. 1272 48

Staphylococcus aureus and Staphylococcus epidermidis ferritin (FtnA and SefA, respectively) homologues are antigenic and highly conserved. A previous study showed that ftnA is a component of the S. aureus PerR regulon with its transcription induced by elevated iron and repressed by PerR, which functions as a manganese-dependent transcriptional repressor. We have further investigated the role of iron and Fur in the regulation of PerR regulon genes ftnA (ferritin), ahpC (alkyl-hydroperoxidase), and mrgA (Dps homologue) and shown that iron has a major role in the regulation of the PerR regulon and hence the oxidative stress response, since in the presence of both iron and manganese, transcription of PerR regulon genes is induced above the repressed levels observed with manganese alone. Furthermore the PerR regulon genes are differentially regulated by metal availability and Fur. First, there is an additional level of PerR-independent regulation of ftnA under low-iron conditions which is not observed with ahpC and mrgA. Second, there is a differential response of these genes to Fur as ftnA expression is constitutive in a fur mutant, while ahpC expression is constitutive under low-Fe/Mn conditions but some repression of ahpC still occurs in the presence of manganese, whereas mrgA expression is still repressed in the fur mutant as in wild-type S. aureus, although there is a decrease in the overall level of mrgA transcription. These studies have also shown that FtnA expression is regulated by growth phase, but maximal transcription of ftnA differs dependent on the growth medium. Moreover, there are significant regulatory differences between the S. aureus and S. epidermidis ferritins, as sefA expression in contrast to that of ftnA is derepressed under low-Fe/Mn ion conditions.
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PMID:The staphylococcal ferritins are differentially regulated in response to iron and manganese and via PerR and Fur. 1474 43


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