A role for sex and a common HFE gene variant in brain iron uptake.

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Duck, Kari A; Neely, Elizabeth B; Simpson, Ian A; Connor, James R

2018-03-01

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood-brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood-brain barrier.

Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.

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Fiorito, Veronica; Geninatti Crich, Simonetta; Silengo, Lorenzo; Aime, Silvio; Altruda, Fiorella; Tolosano, Emanuela

2013-01-01

The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.

Metallofullerenol Inhibits Cellular Iron Uptake by Inducing Transferrin Tetramerization.

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Li, Jinxia; Xing, Xueqing; Sun, Baoyun; Zhao, Yuliang; Wu, Zhonghua

2017-10-18

Herein, A549 tumor cell proliferation was confirmed to be positively dependent on the concentration of Fe 3+ or transferrin (Tf). Gd@C 82 (OH) 22 or C 60 (OH) 22 effectively inhibited the iron uptake and the subsequent proliferation of A549 cells. The conformational changes of Tf mixed with FeCl 3 , GdCl 3 , C 60 (OH) 22 or Gd@C 82 (OH) 22 were obtained by SAXS. The results demonstrate that Tf homodimers can be decomposed into monomers in the presence of FeCl 3 , GdCl 3 or C 60 (OH) 22 , but associated into tetramers in the presence of Gd@C 82 (OH) 22 . The larger change of SAXS shapes between Tf+C 60 (OH) 22 and Tf+FeCl 3 implies that C 60 (OH) 22 is bound to Tf, blocking the iron-binding site. The larger deviation of the SAXS shape from a possible crystal structure of Tf tetramer implies that Gd@C 82 (OH) 22 is bound to the Tf tetramer, thus disturbing iron transport. This study well explains the inhibition mechanism of Gd@C 82 (OH) 22 and C 60 (OH) 22 on the iron uptake and the proliferation of A549 tumor cells and highlights the specific interactions of a nanomedicine with the target biomolecules in cancer therapy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria

International Nuclear Information System (INIS)

Konopka, K.; Romslo, I.; Bergen Univ.

1981-01-01

1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein -1 h -1 , or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is depleted, or the experiments are run under anaerobic conditions. Substrate, depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous irons thus formed is available for heme synthesis. (orig.) [de

Effect of molybdenum and iron supply on molybdenum (99Mo) and iron (59Fe) uptake and activity of certain enzymes in tomato plants grown in sand culture

International Nuclear Information System (INIS)

Chatterjee, C.; Agarwala, S.C.

1979-01-01

Tomato (Lycopersicon esculentum Mill. var. Marglobe) plants were raised under controlled sand culture to study the interaction of molybdenum and iron supply on the uptake of molybdenum and iron and activity of certain enzymes affected by iron and/or molybdenum supply. Iron deficiency caused a decrease in the molybdenum uptake and accentuated the effect of molybdenum deficiency in reducing the uptake and more so the translocation of molybdenum from roots to shoots, thus inducing more severe molybdenum deficiency. The deficiency of iron and molybdenum decreased the activity of catalase, succinate dehydrogenase and nitrate reductase, the most marked decrease being found in plants supplied with both iron and molybdenum at low levels. Changes in the activities of nitrate reductase and catalase can be attributed to the interaction of iron and molybdenum supply in their absorption and translocation. (auth.)

Fob1 and Fob2 Proteins Are Virulence Determinants of Rhizopus oryzae via Facilitating Iron Uptake from Ferrioxamine.

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Mingfu Liu

2015-05-01

Full Text Available Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis, which is most often caused by Rhizopus oryzae. Although the deferoxamine siderophore is not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine. Here we determined that the CBS domain proteins of Fob1 and Fob2 act as receptors on the cell surface of R. oryzae during iron uptake from ferrioxamine. Fob1 and Fob2 cell surface expression was induced in the presence of ferrioxamine and bound radiolabeled ferrioxamine. A R. oryzae strain with targeted reduced Fob1/Fob2 expression was impaired for iron uptake, germinating, and growing on medium with ferrioxamine as the sole source of iron. This strain also exhibited reduced virulence in a deferoxamine-treated, but not the diabetic ketoacidotic (DKA, mouse model of mucormycosis. The mechanism by which R. oryzae obtains iron from ferrioxamine involves the reductase/permease uptake system since the growth on ferrioxamine supplemented medium is associated with elevated reductase activity and the use of the ferrous chelator bathophenanthroline disulfonate abrogates iron uptake and growth on medium supplemented with ferrioxamine as a sole source of iron. Finally, R. oryzae mutants with reduced copies of the high affinity iron permease (FTR1 or with decreased FTR1 expression had an impaired iron uptake from ferrioxamine in vitro and reduced virulence in the deferoxamine-treated mouse model of mucormycosis. These two receptors appear to be conserved in Mucorales, and can be the subject of future novel therapy to maintain the use of deferoxamine for treating iron-overload.

Augmented internalisation of ferroportin to late endosomes impairs iron uptake by enterocyte-like IEC-6 cells.

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Oates, Phillip S; Thomas, Carla

2005-08-01

Absorption of iron occurs by duodenal enterocytes, involving uptake by the divalent metal transporter-1 (DMT1) and release by ferroportin. Ferroportin responds to the hepatocyte-produced 25-amino-acid-peptide hepcidin-25 by undergoing internalisation to late endosomes that impair iron release. Ferroportin is also expressed on the apical membrane of polarised Caco-2 cells, rat intestinal cells and in IEC-6 cells (an intestinal epithelial cell line). A blocking antibody to ferroportin also impairs the uptake, but not the release, of iron. In this study IEC-6 cells were used to study the mechanism of impairment or recovery from impairment produced by the blocking antibody and the fate of DMT1 and ferroportin. Uptake of 1 muM Fe(II) was studied by adding the antibody from time 0 and after adding or removing the antibody once a steady state had been reached. Surface binding, maximum iron transport rate V(max) and transporter affinity (K(m)) were measured after impairment of iron uptake. Ferroportin and DMT1 distribution were assessed by immunofluorescence microscopy. Antibody-mediated impairment, or recovery from impairment, of Fe(II) uptake occurred within minutes. Impairment was lost when the antibody was combined with the immunizing peptide. DMT1 and ferroportin undergo internalisation to late endosomes and, in the presence of the antibody, augmented internalisation of DMT1 and ferroportin caused swelling of late endosomes. Surface binding of Fe(II) and iron transport V(max) were reduced by 50%, indicating that the antibody removed membrane-bound DMT1. The ferroportin antibody induced rapid turnover of membrane ferroportin and DMT1 and its internalisation to late endosomes, resulting in impaired Fe(II) uptake.

UPTAKE OF HEAVY METALS IN BATCH SYSTEMS BY A RECYCLED IRON-BEARING MATERIAL

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An iron-bearing material deriving from surface finishing operations in the manufacturing of cast-iron components demonstrates potential for removal of heavy metals from aqueous waste streams. Batch isotherm and rate experiments were conducted for uptake of cadmium, zinc, and lead...

Analysis of the global ocean sampling (GOS) project for trends in iron uptake by surface ocean microbes.

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Toulza, Eve; Tagliabue, Alessandro; Blain, Stéphane; Piganeau, Gwenael

2012-01-01

Microbial metagenomes are DNA samples of the most abundant, and therefore most successful organisms at the sampling time and location for a given cell size range. The study of microbial communities via their DNA content has revolutionized our understanding of microbial ecology and evolution. Iron availability is a critical resource that limits microbial communities' growth in many oceanic areas. Here, we built a database of 2319 sequences, corresponding to 140 gene families of iron metabolism with a large phylogenetic spread, to explore the microbial strategies of iron acquisition in the ocean's bacterial community. We estimate iron metabolism strategies from metagenome gene content and investigate whether their prevalence varies with dissolved iron concentrations obtained from a biogeochemical model. We show significant quantitative and qualitative variations in iron metabolism pathways, with a higher proportion of iron metabolism genes in low iron environments. We found a striking difference between coastal and open ocean sites regarding Fe(2+) versus Fe(3+) uptake gene prevalence. We also show that non-specific siderophore uptake increases in low iron open ocean environments, suggesting bacteria may acquire iron from natural siderophore-like organic complexes. Despite the lack of knowledge of iron uptake mechanisms in most marine microorganisms, our approach provides insights into how the iron metabolic pathways of microbial communities may vary with seawater iron concentrations.

Effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate in animals: concise communication

International Nuclear Information System (INIS)

Bradley, W.P.; Alderson, P.O.; Weiss, J.F.

1979-01-01

To investigate the effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate, 20 weanling Sprague-Dawley rats were maintained for 6 to 8 weeks on a low-iron diet. Eighteen littermates were maintained on a normal iron diet and served as controls. Animals received 10 μCi Ga-67 citrate, and urine and feces were collected for 48 h. The animals were then killed, tissue samples were obtained, and serum iron and unsaturated iron-binding capacity (UIBC) were measured. The accumulation of Ga-67 in the liver and spleen (% injected dose) was markedly increased in iron-deficient animals and urinary excretion was reduced. Tumor uptake was not significantly different in iron-deficient and control animals, but tumor-to-blood ratios were elevated (p < 0.001) in the iron-deficient animals because of low blood levels of Ga-67. The liver and spleen accumulation of Ga-67 correlated significantly (p < 0.001) with the UIBC. The results show that iron deficiency alters the distribution of Ga-67 citrate, and suggest that the variable liver-spleen uptake seen in clinical Ga-67 images may be explained, in part, by changes in serum iron and UIBC

Gene expression profiling in Entamoeba histolytica identifies key components in iron uptake and metabolism.

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Nora Adriana Hernández-Cuevas

Full Text Available Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron, low-iron medium (around 123 µM iron, iron-deficient medium (around 91 µM iron, and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite.

Gene expression profiling in Entamoeba histolytica identifies key components in iron uptake and metabolism.

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Hernández-Cuevas, Nora Adriana; Weber, Christian; Hon, Chung-Chau; Guillen, Nancy

2014-01-01

Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron), low-iron medium (around 123 µM iron), iron-deficient medium (around 91 µM iron), and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters) and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite.

Genomic insights into the iron uptake mechanisms of the biomining microorganism Acidithiobacillus ferrooxidans.

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Quatrini, Raquel; Jedlicki, Eugenia; Holmes, David S

2005-12-01

Commercial bioleaching of copper and the biooxidation of gold is a cost-effective and environmentally friendly process for metal recovery. A partial genome sequence of the acidophilic, bioleaching bacterium Acidithiobacillus ferrooxidans is available from two public sources. This information has been used to build preliminary models that describe how this microorganism confronts unusually high iron loads in the extremely acidic conditions (pH 2) found in natural environments and in bioleaching operations. A. ferrooxidans contains candidate genes for iron uptake, sensing, storage, and regulation of iron homeostasis. Predicted proteins exhibit significant amino acid similarity with known proteins from neutrophilic organisms, including conservation of functional motifs, permitting their identification by bioinformatics tools and allowing the recognition of common themes in iron transport across distantly related species. However, significant differences in amino acid sequence were detected in pertinent domains that suggest ways in which the periplasmic and outer membrane proteins of A. ferrooxidans maintain structural integrity and relevant protein-protein contacts at low pH. Unexpectedly, the microorganism also contains candidate genes, organized in operon-like structures that potentially encode at least 11 siderophore systems for the uptake of Fe(III), although it does not exhibit genes that could encode the biosynthesis of the siderophores themselves. The presence of multiple Fe(III) uptake systems suggests that A. ferrooxidans can inhabit aerobic environments where iron is scarce and where siderophore producers are present. It may also help to explain why it cannot tolerate high Fe(III) concentrations in bioleaching operations where it is out-competed by Leptospirillum species.

Iron uptake mechanisms in the fish pathogen Tenacibaculum maritimum.

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Avendaño-Herrera, Ruben; Toranzo, Alicia E; Romalde, Jesús L; Lemos, Manuel L; Magariños, Beatriz

2005-11-01

We present here the first evidence of the presence of iron uptake mechanisms in the bacterial fish pathogen Tenacibaculum maritimum. Representative strains of this species, with different serotypes and origins, were examined. All of them were able to grow in the presence of the chelating agent ethylenediamine-di-(o-hydroxyphenyl acetic acid) (EDDHA) and also produced siderophores. Cross-feeding assays suggest that the siderophores produced are closely related. In addition, all T. maritimum strains utilized transferrin, hemin, hemoglobin, and ferric ammonic citrate as iron sources when added to iron-deficient media. Whole cells of all T. maritimum strains, grown under iron-supplemented or iron-restricted conditions, were able to bind hemin, indicating the existence of constitutive binding components located at the T. maritimum cell surface. This was confirmed by the observation that isolated total and outer membrane proteins from all of the strains, regardless of the iron levels of the media, were able to bind hemin, with the outer membranes showing the strongest binding. Proteinase K treatment of whole cells did not affect the hemin binding, indicating that, in addition to proteins, some protease-resistant components could also bind hemin. At least three outer membrane proteins were induced in iron-limiting conditions, and all strains, regardless of their serotype, showed a similar pattern of induced proteins. The results of the present study suggest that T. maritimum possesses at least two different systems of iron acquisition: one involving the synthesis of siderophores and another that allows the utilization of heme groups as iron sources by direct binding.

The effect of iron plaque on uptake and translocation of norfloxacin in rice seedlings grown in paddy soil.

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Yan, Dafang; Ma, Wei; Song, Xiaojing; Bao, Yanyu

2017-03-01

Although the role of iron plaque on rice root surface has been investigated in recent years, its effect on antibiotic uptake remains uncertain. In the study, pot experiment was conducted to investigate the effect of iron plaque on uptake and translocation of norfloxacin (adding 10 and 50 mg·kg -1 treatments) in rice seedlings grown in paddy soil. Iron plaque was induced by adding different amounts of Fe(II) in soil. The results showed that the presence of norfloxacin can decrease the amount of iron plaque induced. After rice with iron plaque induced, norfloxacin was mainly accumulated in iron plaque on root surface, followed by inside root, but its translocation from root to other rice tissues is not observed. Iron plaque played the role of a barrier for norfloxacin uptake into rice roots under high norfloxacin concentration of 50 mg·kg -1 , however not that under low concentration of 10 mg·kg -1 . And the barrier function was the most strongest with adding Fe(II) of 30 mg·kg -1 as combined action of iron plaque and rhizosphere effect. Fluorescence microscope analysis showed that norfloxacin mainly distributed in the outside of root cell, which showed its translocation as apoplastic pathway in rice. Comparing with non-rhizosphere, more norfloxacin was accumulated in rhizosphere soil. Maybe, strong root oxidization (high Eh values) induced more iron oxide formation in rhizosphere and on root surface, which led to norfloxacin's mobility towards to rhizosphere through its strong adsorption of iron oxides and then promoted its uptake by rice on root surface.

Absorption of iron in the aged; investigation of mucosal-uptake, mucosal-transfer and retention of a physiological dose of inorganic iron

International Nuclear Information System (INIS)

Marx, J.J.M.

1976-01-01

Iron (II) and iron (III) uptake by the mucosal cells, the retention in the body, and the mucosal-transport fraction were studied in 40 healthy people over 65 years old, in 30 young adults and in 20 patients with iron-deficiency. The study was performed with 59 Fe as a tracer and 51 Cr as an inert indicator. The radioactivity was measured with a whole body scanner 24 hours and 24 days after ingestion

Iron uptake by Caco-2 cells following in vitro digestion: effects of heat treatments of pork meat and pH of the digests.

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Sørensen, Anne D; Bukhave, Klaus

2010-10-01

The present in vitro studies report on iron uptake by Caco-2 cells from pepsin and pepsin+pancreatin-digested pork meat proteins at pH values between 4.6 and 7 mimicking conditions in the duodenum and the proximal jejunum, respectively. Heat treatment of the pork meat resulted in increased iron uptake from pepsin-digested samples to Caco-2 cells at pH 4.6. The major enhancing effects on iron uptake by Caco-2 cells were observed after pepsin digestion in the pH range 4.6-6.0, whereas the pepsin+pancreatin-digested samples resulted in negligible iron uptake in Caco-2 cells at pH 7. Thus, the results emphasize the importance of separating pepsin-digested and pepsin+pancreatin-digested proteins during in vitro studies on iron availability. Furthermore, the present results showed the pH dependency of iron uptake anticipated. The enhancing effect of ascorbic acid was verified by increased iron uptake from pepsin-digested pork meat samples at pH 4.6, while no effect of ascorbic acid was observed at pH 7 in pepsin+pancreatin-digested samples. Copyright © 2010 Elsevier GmbH. All rights reserved.

Alkaline stress and iron deficiency regulate iron uptake and riboflavin synthesis gene expression differently in root and leaf tissue: implications for iron deficiency chlorosis.

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Hsieh, En-Jung; Waters, Brian M

2016-10-01

Iron (Fe) is an essential mineral that has low solubility in alkaline soils, where its deficiency results in chlorosis. Whether low Fe supply and alkaline pH stress are equivalent is unclear, as they have not been treated as separate variables in molecular physiological studies. Additionally, molecular responses to these stresses have not been studied in leaf and root tissues simultaneously. We tested how plants with the Strategy I Fe uptake system respond to Fe deficiency at mildly acidic and alkaline pH by measuring root ferric chelate reductase (FCR) activity and expression of selected Fe uptake genes and riboflavin synthesis genes. Alkaline pH increased cucumber (Cucumis sativus L.) root FCR activity at full Fe supply, but alkaline stress abolished FCR response to low Fe supply. Alkaline pH or low Fe supply resulted in increased expression of Fe uptake genes, but riboflavin synthesis genes responded to Fe deficiency but not alkalinity. Iron deficiency increased expression of some common genes in roots and leaves, but alkaline stress blocked up-regulation of these genes in Fe-deficient leaves. In roots of the melon (Cucumis melo L.) fefe mutant, in which Fe uptake responses are blocked upstream of Fe uptake genes, alkaline stress or Fe deficiency up-regulation of certain Fe uptake and riboflavin synthesis genes was inhibited, indicating a central role for the FeFe protein. These results suggest a model implicating shoot-to-root signaling of Fe status to induce Fe uptake gene expression in roots. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Ferric reductase genes involved in high-affinity iron uptake are differentially regulated in yeast and hyphae of Candida albicans.

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Jeeves, Rose E; Mason, Robert P; Woodacre, Alexandra; Cashmore, Annette M

2011-09-01

The pathogenic yeast Candida albicans possesses a reductive iron uptake system which is active in iron-restricted conditions. The sequestration of iron by this mechanism initially requires the reduction of free iron to the soluble ferrous form, which is catalysed by ferric reductase proteins. Reduced iron is then taken up into the cell by a complex of a multicopper oxidase protein and an iron transport protein. Multicopper oxidase proteins require copper to function and so reductive iron and copper uptake are inextricably linked. It has previously been established that Fre10 is the major cell surface ferric reductase in C. albicans and that transcription of FRE10 is regulated in response to iron levels. We demonstrate here that Fre10 is also a cupric reductase and that Fre7 also makes a significant contribution to cell surface ferric and cupric reductase activity. It is also shown, for the first time, that transcription of FRE10 and FRE7 is lower in hyphae compared to yeast and that this leads to a corresponding decrease in cell surface ferric, but not cupric, reductase activity. This demonstrates that the regulation of two virulence determinants, the reductive iron uptake system and the morphological form of C. albicans, are linked. Copyright © 2011 John Wiley & Sons, Ltd.

The Porphyromonas gingivalis ferric uptake regulator orthologue does not regulate iron homeostasis

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Catherine Butler

2015-09-01

Full Text Available Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that has an absolute requirement for iron which it transports from the host as heme and/or Fe2+. Iron transport must be regulated to prevent toxic effects from excess metal in the cell. P. gingivalis has one ferric uptake regulator (Fur orthologue encoded in its genome called Har, which would be expected to regulate the transport and usage of iron within this bacterium. As a gene regulator, inactivation of Har should result in changes in gene expression of several genes compared to the wild-type. This dataset (GEO accession number GSE37099 provides information on expression levels of genes in P. gingivalis in the absence of Har. Surprisingly, these genes do not relate to iron homeostasis.

Mutually Exclusive Alterations in Secondary Metabolism Are Critical for the Uptake of Insoluble Iron Compounds by Arabidopsis and Medicago truncatula1[C][W

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Rodríguez-Celma, Jorge; Lin, Wen-Dar; Fu, Guin-Mau; Abadía, Javier; López-Millán, Ana-Flor; Schmidt, Wolfgang

2013-01-01

The generally low bioavailability of iron in aerobic soil systems forced plants to evolve sophisticated genetic strategies to improve the acquisition of iron from sparingly soluble and immobile iron pools. To distinguish between conserved and species-dependent components of such strategies, we analyzed iron deficiency-induced changes in the transcriptome of two model species, Arabidopsis (Arabidopsis thaliana) and Medicago truncatula. Transcriptional profiling by RNA sequencing revealed a massive up-regulation of genes coding for enzymes involved in riboflavin biosynthesis in M. truncatula and phenylpropanoid synthesis in Arabidopsis upon iron deficiency. Coexpression and promoter analysis indicated that the synthesis of flavins and phenylpropanoids is tightly linked to and putatively coregulated with other genes encoding proteins involved in iron uptake. We further provide evidence that the production and secretion of phenolic compounds is critical for the uptake of iron from sources with low bioavailability but dispensable under conditions where iron is readily available. In Arabidopsis, homozygous mutations in the Fe(II)- and 2-oxoglutarate-dependent dioxygenase family gene F6′H1 and defects in the expression of PLEIOTROPIC DRUG RESISTANCE9, encoding a putative efflux transporter for products from the phenylpropanoid pathway, compromised iron uptake from an iron source of low bioavailability. Both mutants were partially rescued when grown alongside wild-type Arabidopsis or M. truncatula seedlings, presumably by secreted phenolics and flavins. We concluded that production and secretion of compounds that facilitate the uptake of iron is an essential but poorly understood aspect of the reduction-based iron acquisition strategy, which is likely to contribute substantially to the efficiency of iron uptake in natural conditions. PMID:23735511

Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.

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Sarah Straud

2010-07-01

Full Text Available Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant of V-ATPase sensitivity in several cancer cell lines. One of the most sensitive cell lines, melanoma derived SK-Mel-5, over-expresses the iron efflux transporter ferroportin and has decreased expression of proteins involved in iron uptake, suggesting that it actively suppresses cytoplasmic iron. SK-Mel-5 cells have increased production of reactive oxygen species and may be seeking to limit additional production of ROS by iron.

Nitrogen uptake and rate-limiting step in low-temperature nitriding of iron

NARCIS (Netherlands)

Inia, DK; Vredenberg, AM; Habraken, FHPM; Boerma, DO

1999-01-01

Recently, a method to nitride iron in NH3 ambients at low temperature (225-350 degrees C) has been developed. In this method, the Fe is covered with a thin (similar to 40 nm) Ni layer, which acts as a catalyst for the nitriding process. From experiments, in which the amount of nitrogen uptake is

The effect of the administration of iron on Ga-67 uptake in animal tumor and biodistribution

International Nuclear Information System (INIS)

Furukawa, Keiji

1983-01-01

In 1979 Larson reported that the uptake of Ga-67 in tumor cell was preceded by binding of the Ga-67 to transferrin. Since that time there have been many papers concerning changes in Ga-67 accumulation in experimental tumor by administration of iron before and after Ga-67 injection. This study was undertaken in the attempt to discern what changes are produced in Ga-67 images of tumor-bearing rabbits (VX-II) when iron was administered before and after Ga-67 injection. Additionally, the relationships between the change in the serum iron concentration in the tumor tissue in mice bearing Ehrlich's ascites tumor were studied. The following results were obtained. 1) The tumor uptake and biodistribution of Ga-67 following administration of iron in the form of Fesin (saccharated ferric oxide) or ferric-citrate is obviously diminished. This iron administration leads to an elevated excretion of Ga-67 from tumor and other organs except from bone. From this results, it was found that Ga-67 binds somewhat less avidity than iron to various iron transport protein. Accordingly, Ga-67 biodistribution may be markedly influenced by iron-loading. 2) The Ga-67 activity in blood following administration of iron was noted to suddenly markedly decrease. However, 24-48 hours after iron injection the Ga-67 activity in blood gradually increased. This result suggests that the Ga-67 displaced into the extravascular space by iron-loading reentered the vascular space when the iron concentration of serum returned to normal. 3) The accumulation of Ga-67 in the tumor and soft tissues was slightly decreased compared with controls after iron administration. However, the tumor to blood ratio (T/B) of Ga-67 in mice by iron loading was several time greater than that of Ga-67 alone because the clearance of Ga-67 from the blood was more accelated than that of tumor. The large tumor to blood ratio (T/B) would be advantageous in obtaining a more distinct tumor scan. (author)

Phosphate dynamics in an acidic mountain stream: Interactions involving algal uptake, sorption by iron oxide, and photoreduction

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Tate, Cathy M.; Broshears, Robert E.; McKnight, Diane M.

1995-01-01

Acid mine drainage streams in the Rocky Mountains typically have few algal species and abundant iron oxide deposits which can sorb phosphate. An instream injection of radiolabeled phosphate (32P0,) into St. Kevin Gulch, an acid mine drainage stream, was used to test the ability of a dominant algal species, Ulothrix sp., to rapidly assimilate phosphate. Approximately 90% of the injected phosphate was removed from the water column in the 175-m stream reach. When shaded stream reaches were exposed to full sunlight after the injection ended, photoreductive dissolution of iron oxide released sorbed 32P, which was then also removed downstream. The removal from the stream was modeled as a first-order process by using a reactive solute transport transient storage model. Concentrations of 32P mass-’ of algae were typically lo-fold greater than concentrations in hydrous iron oxides. During the injection, concentrations of 32P increased in the cellular P pool containing soluble, low-molecular-weight compounds and confirmed direct algal uptake of 32P0, from water. Mass balance calculations indicated that algal uptake and sorption on iron oxides were significant in removing phosphate. We conclude that in stream ecosystems, PO, sorbed by iron oxides can act as a dynamic nutrient reservoir regulated by photoreduction.

Ligand-free, protein-bound technetium-99m iron-dextran enhancement of technetium pyrophosphate uptake in tumours

International Nuclear Information System (INIS)

Pojer, P.M.; Jakovljevic, A.C.; Wise, K.N.

1985-01-01

The biodistribution of technetium-99m was studied in T-cell lymphoma and selected organs of iron-dextran treated and control mice given technetium-99m pyrophosphate. The results showed that high serum iron levels increased tumour uptake of technetium pyrophosphate. This supports the hypothesis that technetium, in common with other metal-based tumour seeking radiopharmaceuticals, is transported to tumours as a ligand-free protein-bound cation. (U.K.)

The iron uptake repressor Fep1 in the fission yeast binds Fe-S cluster through conserved cysteines

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyo-Jin; Lee, Kang-Lok; Kim, Kyoung-Dong; Roe, Jung-Hye, E-mail: jhroe@snu.ac.kr

2016-09-09

Iron homeostasis is tightly regulated since iron is an essential but toxic element in the cell. The GATA-type transcription factor Fep1 and its orthologs contribute to iron homeostasis in many fungi by repressing genes for iron uptake when intracellular iron is high. Even though the function and interaction partners of Fep1 have been elucidated extensively In Schizosaccharomyces pombe, the mechanism behind iron-sensing by Fep1 remains elusive. It has been reported that Fep1 interacts with Fe-S-containing monothiol glutaredoxin Grx4 and Grx4-Fra2 complex. In this study, we demonstrate that Fep1 also binds iron, in the form of Fe-S cluster. Spectroscopic and biochemical analyses of as isolated and reconstituted Fep1 suggest that the dimeric Fep1 binds Fe-S clusters. The mutation study revealed that the cluster-binding depended on the conserved cysteines located between the two zinc fingers in the DNA binding domain. EPR analyses revealed [Fe-S]-specific peaks indicative of mixed presence of [2Fe-2S], [3Fe-4S], or [4Fe-4S]. The finding that Fep1 is an Fe-S protein fits nicely with the model that the Fe-S-trafficking Grx4 senses intracellular iron environment and modulates the activity of Fep1. - Highlights: • Fep1, a prototype fungal iron uptake regulator, was isolated stably from Schizosaccharomyces pombe. • Fep1 exhibits UV–visible absorption spectrum, characteristic of [Fe-S] proteins. • The iron and sulfide contents in purified or reconstituted Fep1 also support [Fe-S]. • The conserved cysteines are critical for [Fe-S]-binding. • EPR spectra at 5 K and 123 K suggest a mixed population of [Fe-S].

Ferric reductase activity of low molecular weight human milk fraction is associated with enhanced iron solubility and uptake in Caco-2 cells.

Science.gov (United States)

Pullakhandam, Raghu; Nair, Madhavan Krishnapillai; Kasula, Sunanda; Kilari, Sreenivasulu; Thippande, Tippeswamy Gowda

2008-09-19

It is known that the fractional absorption of extrinsic iron from human milk is higher in infants and adults. A low molecular weight milk fraction has been proposed to increase the bioavailability of iron from human milk. Nevertheless, the mechanisms remained elusive. Here in we demonstrate ferric reductase activity (Km7.73x10(-6)M) in low molecular weight human milk fraction (10kF, filtrate derived from ultra filtration of milk whey through 10kDa cutoff membrane), which increased ferric iron solubility and iron uptake in Caco-2 cells. The 10kF fraction was as effective as ascorbic acid (1:20 iron to ascorbic acid) in increasing the ferric iron solubility and uptake in Caco-2 cells. Further, gel filtration chromatography on peptide column led to co-elution of ferric reductase and iron solubilization activities at an apparent molecular mass of iron in Caco-2 cells. Thus, it is concluded that human milk possesses ferric reductase activity and is associated with ferric iron solubilization and enhanced absorption.

The role of iron uptake in pathogenicity and symbiosis in Photorhabdus luminescens TT01

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Joyce Susan A

2010-06-01

Full Text Available Abstract Background Photorhabdus are Gram negative bacteria that are pathogenic to insect larvae whilst also having a mutualistic interaction with nematodes from the family Heterorhabditis. Iron is an essential nutrient and bacteria have different mechanisms for obtaining both the ferrous (Fe2+ and ferric (Fe3+ forms of this metal from their environments. In this study we were interested in analyzing the role of Fe3+ and Fe2+ iron uptake systems in the ability of Photorhabdus to interact with its invertebrate hosts. Results We constructed targeted deletion mutants of exbD, feoABC and yfeABCD in P. luminescens TT01. The exbD mutant was predicted to be crippled in its ability to obtain Fe3+ and we show that this mutant does not grow well in iron-limited media. We also show that this mutant was avirulent to the insect but was unaffected in its symbiotic interaction with Heterorhabditis. Furthermore we show that a mutation in feoABC (encoding a predicted Fe2+ permease was unaffected in both virulence and symbiosis whilst the divalent cation transporter encoded by yfeABCD is required for virulence in the Tobacco Hornworm, Manduca sexta (Lepidoptera but not in the Greater Wax Moth, Galleria mellonella (Lepidoptera. Moreover the Yfe transporter also appears to have a role during colonization of the IJ stage of the nematode. Conclusion In this study we show that iron uptake (via the TonB complex and the Yfe transporter is important for the virulence of P. luminescens to insect larvae. Moreover this study also reveals that the Yfe transporter appears to be involved in Mn2+-uptake during growth in the gut lumen of the IJ nematode. Therefore, the Yfe transporter in P. luminescens TT01 is important during colonization of both the insect and nematode and, moreover, the metal ion transported by this pathway is host-dependent.

Is the effect of silicon on rice uptake of arsenate (AsV) related to internal silicon concentrations, iron plaque and phosphate nutrition?

International Nuclear Information System (INIS)

Guo, W.; Zhu, Y.-G.; Liu, W.-J.; Liang, Y.-C.; Geng, C.-N.; Wang, S.-G.

2007-01-01

Solution culture experiments were conducted to investigate the effects of silicon (Si) on arsenate (As V ) uptake by rice. The addition of Si to the pretreatment or uptake solution significantly decreased shoot and root As concentrations (P < 0.001 and P < 0.05). The presence of Si in the pretreatment or uptake solution also significantly decreased shoot P concentrations (P < 0.001). The data demonstrated that both internal and external Si inhibited the uptake of As and P. Results of As uptake kinetics showed that the mechanism of the effect of Si on arsenate uptake is not caused by direct competition for active sites of transporters with As. The effect of Si on As uptake was not entirely mediated through the effect of Si on P uptake. Although the addition of Si to pretreatment solutions still significantly decreased shoot and root As concentrations, the extent of reduction became smaller when rice roots were coated with iron plaque. - Arsenate uptake by rice seedlings is affected by both Si (internal and external) and iron plaque on root surface

The iron-regulated transporter 1 plays an essential role in uptake, translocation and grain-loading of manganese, but not iron, in barley

DEFF Research Database (Denmark)

Long, Lizhi; Persson, Daniel Olaf; Duan, Fengying

2018-01-01

Transporters involved in manganese (Mn) uptake and intracellular Mn homeostasis in Arabidopsis and rice are well characterized, while much less is known for barley, which is particularly prone to Mn deficiency. In this study we have investigated the role of the iron-regulated transporter 1 (IRT1...

Iron plaque formation and heavy metal uptake in Spartina alterniflora at different tidal levels and waterlogging conditions.

Science.gov (United States)

Xu, Yan; Sun, Xiangli; Zhang, Qiqiong; Li, Xiuzhen; Yan, Zhongzheng

2018-05-30

Tidal flat elevation in the estuarine wetland determines the tidal flooding time and flooding frequency, which will inevitably affect the formation of iron plaque and accumulations of heavy metals (HMs) in wetland plants. The present study investigated the formation of iron plaque and HM's (copper, zinc, lead, and chromium) accumulation in S. alterniflora, a typical estuarine wetland species, at different tidal flat elevations (low, middle and high) in filed and at different time (3, 6, 9, 12 h per day) of waterlogging treatment in greenhouse conditions. Results showed that the accumulation of copper, zinc, lead, and chromium in S. alterniflora was proportional to the exchangeable fraction of these metals in the sediments, which generally increased with the increase of waterlogging time, whereas the formations of iron plaque in roots decreased with the increase of waterlogging time. Under field conditions, the uptake of copper and zinc in the different parts of the plants generally increased with the tidal levels despite the decrease in the metals' exchangeable fraction with increasing tidal levels. The formation of iron plaque was found to be highest in the middle tidal positions and significantly lower in low and high tidal positions. Longer waterlogging time increased the metals' accumulation but decreased the formation of iron plaque in S. alterniflora. The binding of metal ions on iron plaque helped impede the uptake and accumulation of copper and chromium in S. alterniflora. Copyright © 2018 Elsevier Inc. All rights reserved.

Homogenization, lyophilization or acid-extraction of meat products improves iron uptake from cereal-meat product combinations in an in vitro digestion/Caco-2 cell model.

Science.gov (United States)

Pachón, Helena; Stoltzfus, Rebecca J; Glahn, Raymond P

2009-03-01

The effect of processing (homogenization, lyophilization, acid-extraction) meat products on iron uptake from meat combined with uncooked iron-fortified cereal was evaluated using an in vitro digestion/Caco-2 cell model. Beef was cooked, blended to create smaller meat particles, and combined with electrolytic iron-fortified infant rice cereal. Chicken liver was cooked and blended, lyophilized, or acid-extracted, and combined with FeSO4-fortified wheat flour. In the beef-cereal combination, Caco-2 cell iron uptake, assessed by measuring the ferritin formed by cells, was greater when the beef was blended for the greatest amount of time (360 s) compared with 30 s (P meat products on iron absorption in iron-fortified cereals.

Iron Availability in Tropical Soils and Iron Uptake by Plants

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Guilherme Furlan Mielki

Full Text Available ABSTRACT Given the increase in crop yields and the expansion of agriculture in low fertility soils, deficiency of micronutrients, such as iron, in plants grown in tropical soils has been observed. The aim of this study was to evaluate Fe availability and Fe uptake by corn (Zea mays L. plants in 13 different soils, at two depths. Iron was extracted by Mehlich-1, Mehlich-3, and CaCl2 (Fe-CC and was fractionated in forms related to low (Feo and high (Fed crystallinity pedogenic oxyhydroxides, and organic matter (Fep using ammonium oxalate, dithionite-citrate, and sodium pyrophosphate, respectively. In order to relate Fe availability to soil properties and plant growth, an experiment was carried out in a semi-hydroponic system in which part of the roots developed in a nutrient solution (without Fe and part in the soil (the only source of Fe. Forty-five days after seeding, we quantified shoot dry matter and leaf Fe concentration and content. Fed levels were high, from 5 to 132 g kg-1, and Feo and Fe-CC levels were low, indicating the predominance of Fe as crystalline oxyhydroxides and a low content of Fe readily available to plants. The extraction solutions showed significant correlations with various soil properties, many common to both, indicating that they act similarly. The correlation between the Mehlich-1 and Mehlich-3 extraction solutions was highly significant. However, these two extraction methods were inefficient in predicting Fe availability to plants. There was a positive correlation between dry matter and Fe levels in plant shoots, even within the ranges considered adequate in the soil and in the plant. Dry matter production and leaf Fe concentration and content were positively correlated with Fep concentration, indicating that the Fe fraction related to soil organic matter most contributes to Fe availability to plants.

Does a voltage-sensitive outer envelope transport mechanism contributes to the chloroplast iron uptake?

Science.gov (United States)

Solti, Ádám; Kovács, Krisztina; Müller, Brigitta; Vázquez, Saúl; Hamar, Éva; Pham, Hong Diep; Tóth, Brigitta; Abadía, Javier; Fodor, Ferenc

2016-12-01

Based on the effects of inorganic salts on chloroplast Fe uptake, the presence of a voltage-dependent step is proposed to play a role in Fe uptake through the outer envelope. Although iron (Fe) plays a crucial role in chloroplast physiology, only few pieces of information are available on the mechanisms of chloroplast Fe acquisition. Here, the effect of inorganic salts on the Fe uptake of intact chloroplasts was tested, assessing Fe and transition metal uptake using bathophenantroline-based spectrophotometric detection and plasma emission-coupled mass spectrometry, respectively. The microenvironment of Fe was studied by Mössbauer spectroscopy. Transition metal cations (Cd 2+ , Zn 2+ , and Mn 2+ ) enhanced, whereas oxoanions (NO 3 - , SO 4 2- , and BO 3 3- ) reduced the chloroplast Fe uptake. The effect was insensitive to diuron (DCMU), an inhibitor of chloroplast inner envelope-associated Fe uptake. The inorganic salts affected neither Fe forms in the uptake assay buffer nor those incorporated into the chloroplasts. The significantly lower Zn and Mn uptake compared to that of Fe indicates that different mechanisms/transporters are involved in their acquisition. The enhancing effect of transition metals on chloroplast Fe uptake is likely related to outer envelope-associated processes, since divalent metal cations are known to inhibit Fe 2+ transport across the inner envelope. Thus, a voltage-dependent step is proposed to play a role in Fe uptake through the chloroplast outer envelope on the basis of the contrasting effects of transition metal cations and oxoaninons.

Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

International Nuclear Information System (INIS)

Ayala, Vanessa; Herrera, Adriana P.; Latorre-Esteves, Magda; Torres-Lugo, Madeline; Rinaldi, Carlos

2013-01-01

Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle–cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethyl-substituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine–silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33–45 nm. Surface charge of carboxymethyl-substituted dextran-coated nanoparticles ranged from −50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle–cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions

Effect of surface charge on the colloidal stability and in vitro uptake of carboxymethyl dextran-coated iron oxide nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Ayala, Vanessa; Herrera, Adriana P.; Latorre-Esteves, Magda; Torres-Lugo, Madeline [University of Puerto Rico, Department of Chemical Engineering (United States); Rinaldi, Carlos, E-mail: carlos.rinaldi@bme.ufl.edu [University of Florida, J. Crayton Pruitt Family Department of Biomedical Engineering (United States)

2013-08-15

Nanoparticle physicochemical properties such as surface charge are considered to play an important role in cellular uptake and particle-cell interactions. In order to systematically evaluate the role of surface charge on the uptake of iron oxide nanoparticles, we prepared carboxymethyl-substituted dextrans with different degrees of substitution, ranging from 38 to 5 groups per chain, and reacted them using carbodiimide chemistry with amine-silane-coated iron oxide nanoparticles with narrow size distributions in the range of 33-45 nm. Surface charge of carboxymethyl-substituted dextran-coated nanoparticles ranged from -50 to 5 mV as determined by zeta potential measurements, and was dependent on the number of carboxymethyl groups incorporated in the dextran chains. Nanoparticles were incubated with CaCo-2 human colon cancer cells. Nanoparticle-cell interactions were observed by confocal laser scanning microscopy and uptake was quantified by elemental analysis using inductively coupled plasma mass spectroscopy. Mechanisms of internalization were inferred using pharmacological inhibitors for fluid-phase, clathrin-mediated, and caveola-mediated endocytosis. Results showed increased uptake for nanoparticles with greater negative charge. Internalization patterns suggest that uptake of the most negatively charged particles occurs via non-specific interactions.

Can iron plaque affect Sb(III) and Sb(V) uptake by plants under hydroponic conditions

NARCIS (Netherlands)

Ji, Ying; Lenz, Markus; Lenz, Markus; Schulin, Rainer; Tandy, Susan

2018-01-01

Antimony (Sb) contamination of soils is of concern due to h uman activities such as recycling of Sb containing Pb acid batteries, shooting and mining. However Sb uptake by plants is poorly documented, especially when plants are growing on waterlogged soils and iron plaques form on their roots. The

Placental iron uptake and its regulation

NARCIS (Netherlands)

M. Bierings (Marc)

1989-01-01

textabstractIron transport in pregnancy is an active one-way process, from mother to fetus. Early in gestation fetal iron needs are low, and so is trans-placental transport, but as erythropoiesis develops, rising fetal iron needs are met by trans-placental iron transport. Apparently, the fetus

Restoration of growth by manganese in a mutant strain of Escherichia coli lacking most known iron and manganese uptake systems

DEFF Research Database (Denmark)

Taudte, Nadine; German, Nadezhda; Zhu, Yong-Guan

2016-01-01

The interplay of manganese and iron homeostasis and oxidative stress in Escherichia coli can give important insights into survival of bacteria in the phagosome and under differing iron or manganese bioavailabilities. Here, we characterized a mutant strain devoid of all know iron/manganese-uptake ......The interplay of manganese and iron homeostasis and oxidative stress in Escherichia coli can give important insights into survival of bacteria in the phagosome and under differing iron or manganese bioavailabilities. Here, we characterized a mutant strain devoid of all know iron...

The use of pulsed magnetic fields to increase the uptake of iron oxide nanoparticles by living cells

Czech Academy of Sciences Publication Activity Database

Uzhytchak, M.; Lynnyk, A.; Zablotskyy, V.; Dempsey, N.M.; Dias, A.L.; Bonfim, M.; Lunova, M.; Jirsa, M.; Kubinová, Šárka; Lunov, O.; Dejneka, A.

2017-01-01

Roč. 111, č. 24 (2017), s. 243703 ISSN 0003-6951 Institutional support: RVO:68378041 Keywords : pulsed magnetic fields * increase the uptake * iron oxide * living cells Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.411, year: 2016

Magnetic separation of algae genetically modified for increased intracellular iron uptake

Energy Technology Data Exchange (ETDEWEB)

Buck, Amy [Case Western Reserve University, Cleveland, OH (United States); Cleveland Clinic, Cleveland, OH (United States); Moore, Lee R. [Cleveland Clinic, Cleveland, OH (United States); Lane, Christopher D.; Kumar, Anil; Stroff, Clayton; White, Nicolas [Phycal Inc., Cleveland, OH (United States); Xue, Wei; Chalmers, Jeffrey J. [The Ohio State University, Columbus, OH (United States); Zborowski, Maciej, E-mail: zborowm@ccf.org [Cleveland Clinic, Cleveland, OH (United States)

2015-04-15

Algae were investigated in the past as a potential source of biofuel and other useful chemical derivatives. Magnetic separation of algae by iron oxide nanoparticle binding to cells has been proposed by others for dewatering of cellular mass prior to lipid extraction. We have investigated feasibility of magnetic separation based on the presence of natural iron stores in the cell, such as the ferritin in Auxenochlorella protothecoides (A. protothecoides) strains. The A. protothecoides cell constructs were tested for inserted genes and for increased intracellular iron concentration by inductively coupled plasma atomic absorption (ICP–AA). They were grown in Sueoka’s modified high salt media with added vitamin B1 and increasing concentration of soluble iron compound (FeCl{sub 3} EDTA, from 1× to 8× compared to baseline). The cell magnetic separation conditions were tested using a thin rectangular flow channel pressed against interpolar gaps of a permanent magnet forming a separation system of a well-defined fluid flow and magnetic fringing field geometry (up to 2.2 T and 1000 T/m) dubbed “magnetic deposition microscopy”, or MDM. The presence of magnetic cells in suspension was detected by formation of characteristic deposition bands at the edges of the magnet interpolar gaps, amenable to optical scanning and microscopic examination. The results demonstrated increasing cellular Fe uptake with increasing Fe concentration in the culture media in wild type strain and in selected genetically-modified constructs, leading to magnetic separation without magnetic particle binding. The throughput in this study is not sufficient for an economical scale harvest. - Highlights: • Auxenochlorella protothecoides algae were genetically modified for biofuel production. • Algal iron metabolism was sufficient for their label-less magnetic separation. • High magnetic field and low flow required make the separation scale-up uneconomical.

Magnetic separation of algae genetically modified for increased intracellular iron uptake

International Nuclear Information System (INIS)

Buck, Amy; Moore, Lee R.; Lane, Christopher D.; Kumar, Anil; Stroff, Clayton; White, Nicolas; Xue, Wei; Chalmers, Jeffrey J.; Zborowski, Maciej

2015-01-01

Algae were investigated in the past as a potential source of biofuel and other useful chemical derivatives. Magnetic separation of algae by iron oxide nanoparticle binding to cells has been proposed by others for dewatering of cellular mass prior to lipid extraction. We have investigated feasibility of magnetic separation based on the presence of natural iron stores in the cell, such as the ferritin in Auxenochlorella protothecoides (A. protothecoides) strains. The A. protothecoides cell constructs were tested for inserted genes and for increased intracellular iron concentration by inductively coupled plasma atomic absorption (ICP–AA). They were grown in Sueoka’s modified high salt media with added vitamin B1 and increasing concentration of soluble iron compound (FeCl 3 EDTA, from 1× to 8× compared to baseline). The cell magnetic separation conditions were tested using a thin rectangular flow channel pressed against interpolar gaps of a permanent magnet forming a separation system of a well-defined fluid flow and magnetic fringing field geometry (up to 2.2 T and 1000 T/m) dubbed “magnetic deposition microscopy”, or MDM. The presence of magnetic cells in suspension was detected by formation of characteristic deposition bands at the edges of the magnet interpolar gaps, amenable to optical scanning and microscopic examination. The results demonstrated increasing cellular Fe uptake with increasing Fe concentration in the culture media in wild type strain and in selected genetically-modified constructs, leading to magnetic separation without magnetic particle binding. The throughput in this study is not sufficient for an economical scale harvest. - Highlights: • Auxenochlorella protothecoides algae were genetically modified for biofuel production. • Algal iron metabolism was sufficient for their label-less magnetic separation. • High magnetic field and low flow required make the separation scale-up uneconomical

Influence of Rapeseed Cake on Iron Plaque Formation and Cd Uptake by Rice (Oryza sativa L.) Seedlings Exposed to Excess Cd.

Science.gov (United States)

Yang, Wen-Tao; Zhou, Hang; Gu, Jiao-Feng; Zeng, Qing-Ru; Liao, Bo-Han

2017-11-01

A soil spiking experiment at two Cd levels (0.72 and 5.20 mg kg -1 ) was conducted to investigate the effects of rapeseed cake (RSC) at application rates of 0%, 0.75%, 1.5%, and 3.0% (w/w) on iron plaque formation and Cd uptake by rice (Oryza sativa L.) seedlings. The use of RSC did result in a sharp decrease in soil bioavailability of Cd and a significant increase in rice growth, soil pH and organic matter. Application of RSC increased the amount of iron plaque formation and this effectively inhibited the uptake and translocation of Cd into the rice seedlings. RSC was an effective organic additive for increasing rice growth and reducing Cd uptake by rice plant, simultaneously. These results could be used as a reference for the safety use of Cd polluted paddy soil.

Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

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Joao Arezes

Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

Iron bioavailability in two commercial cultivars of wheat: comparison between wholegrain and white flour and the effects of nicotianamine and 2'-deoxymugineic acid on iron uptake into Caco-2 cells.

Science.gov (United States)

Eagling, Tristan; Wawer, Anna A; Shewry, Peter R; Zhao, Fang-Jie; Fairweather-Tait, Susan J

2014-10-22

Iron bioavailability in unleavened white and wholegrain bread made from two commercial wheat varieties was assessed by measuring ferritin production in Caco-2 cells. The breads were subjected to simulated gastrointestinal digestion and the digests applied to the Caco-2 cells. Although Riband grain contained a lower iron concentration than Rialto, iron bioavailability was higher. No iron was taken up by the cells from white bread made from Rialto flour or from wholegrain bread from either variety, but Riband white bread produced a small ferritin response. The results probably relate to differences in phytate content of the breads, although iron in soluble monoferric phytate was demonstrated to be bioavailable in the cell model. Nicotianamine, an iron chelator in plants involved in iron transport, was a more potent enhancer of iron uptake into Caco-2 cells than ascorbic acid or 2'-deoxymugineic acid, another metal chelator present in plants.

The effect of neutral-surface iron oxide nanoparticles on cellular uptake and signaling pathways

Directory of Open Access Journals (Sweden)

Kim E

2016-09-01

Full Text Available Eunjoo Kim,1 Joon Mee Kim,2 Lucia Kim,2 Suk Jin Choi,2 In Suh Park,2 Jee Young Han,2 Young Chae Chu,2 Eun Sook Choi,1 Kun Na,3 Soon-Sun Hong4 1Division of Nano and Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST, Daegu, 2Department of Pathology, Inha University College of Medicine, Incheon, 3Department of Biotechnology, Catholic University of Korea, Bucheon, 4Department of Biomedical Sciences, Inha University College of Medicine, Incheon, South Korea Abstract: In recent years, iron oxide nanoparticles (IONPs have been applied widely to biomedical fields. However, the relationship between the physicochemical properties of IONPs and their biological behavior is not fully understood yet. We prepared 3-methacryloxypropyl­trimethoxysilane (MPS-coated IONPs, which have a neutral hydrophobic surface, and compared their biological behavior to that of Resovist (ferucarbotran, a commercialized IONP formulation modified with carboxymethyl dextran. The rate of MPS-IONP uptake by human aortic endothelial cells (HAoECs was higher than ferucarbotran uptake, indicating that the neutral hydrophobic nature of MPS-IONPs allowed them to be absorbed more readily through the plasma membrane. However, the signaling pathways activated by MPS-IONPs and ferucarbotran were comparable, suggesting that surface charge is not a key factor for inducing changes in HAoECs. In vivo fate analysis showed that MPS-IONPs accumulated for longer periods in tissues than hydrophilic ferucarbotran. These findings could enlarge our understanding of NP behavior for advanced applications in the biomedical field. Keywords: iron oxide nanoparticles, neutral hydrophobic surface, signaling pathway, uptake, accumulation, reactive oxygen species (ROS

[Effect of selenium on the uptake and translocation of manganese, iron, phosphorus and selenium in rice (Oryza sativa L.)].

Science.gov (United States)

Hu, Ying; Huang, Yi-Zong; Huang, Yan-Chao; Liu, Yun-Xia; Liang, Jian-Hong

2013-10-01

A pot experiment was conducted to clarify the effect of selenium on the uptake and translocation of manganese (Mn), iron (Fe) , phosphorus (P) and selenium (Se) in rice ( Oryza sativa L.). The results showed that addition of Se led to the significant increase of Se concentration in iron plaque on the root surface, root, shoot, husk and brown rice, and significant decrease of Mn concentration in shoot, husk and brown rice. At the Se concentrations of 0.5 and 1.0 mg.kg-1 in soil, Mn concentrations in rice shoot decreased by 32. 2% and 35.0% respectively, in husk 22.0% and 42.6% , in brown rice 27.5% and 28.5% , compared with the Se-free treatment. There was no significant effect of Se on the P and Fe concentrations in every parts of rice, except for Fe concentrations in husk. The translocation of P and Fe from iron plaque, root, shoot and husk to brown rice was not significantly affected by Se addition, but Mn translocation from iron plaque and root to brown rice was significantly inhibited by Se addition. Addition of 1.0 mg.kg-1. Se resulted in the decrease of translocation factor from iron plaque and root to brown rice by 38.9% and 37.9%, respectively, compared with the control treatment. The distribution ratios of Mn, Fe, P and Se in iron plaque, root, shoot, husk and brown rice were also affected by Se addition. The results indicated that Mn uptake, accumulation and translocation in rice could be decreased by the addition of Se in soil, therefore, Se addition could reduce the Mn harm to human health through food chain.

Mitochondrial Iron Transport and Homeostasis in Plants

Directory of Open Access Journals (Sweden)

Anshika eJain

2013-09-01

Full Text Available Iron (Fe is an essential nutrient for plants and although the mechanisms controlling iron uptake from the soil are relatively well understood, comparatively little is known about subcellular trafficking of iron in plant cells. Mitochondria represent a significant iron sink within cells, as iron is required for the proper functioning of respiratory chain protein complexes. Mitochondria are a site of Fe-S cluster synthesis, and possibly heme synthesis as well. Here we review recent insights into the molecular mechanisms controlling mitochondrial iron transport and homeostasis. We focus on the recent identification of a mitochondrial iron uptake transporter in rice and a possible role for metalloreductases in iron uptake by mitochondria. In addition, we highlight recent advances in mitochondrial iron homeostasis with an emphasis on the roles of frataxin and ferritin in iron trafficking and storage within mitochondria.

Physicochemical characterization of mineral (iron/zinc) bound caseinate and their mineral uptake in Caco-2 cells.

Science.gov (United States)

Shilpashree, B G; Arora, Sumit; Kapila, Suman; Sharma, Vivek

2018-08-15

Milk proteins (especially caseins) are widely accepted as good vehicle for the delivery of various bioactive compounds including minerals. Succinylation is one of the most acceptable chemical modification techniques to enhance the mineral binding ability of caseins. Addition of minerals to succinylated proteins may alter their physicochemical and biochemical properties. Physicochemical characteristics of succinylated sodium caseinate (S.NaCN)-mineral (iron/zinc) complexes were elucidated. Chromatographic behaviour and fluorescence intensity confirmed the structural modification of S.NaCN upon binding with minerals. The bound mineral from protein complexes showed significantly higher (P < 0.05) in vitro bioavailability (mineral uptake) than mineral salts in Caco-2 cells. Also, iron bound S.NaCN showed higher cellular ferritin formation than iron in its free form. These mineral bound protein complexes with improved bioavailability could safely replace inorganic fortificants in various functional food formulations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hepatocellular carcinoma with marginal superparamagnetic iron oxide uptake on T2*-weighted magnetic resonance imaging: Histopathologic correlation

International Nuclear Information System (INIS)

Ishigami, Kousei; Tajima, Tsuyoshi; Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Kakihara, Daisuke; Nakayama, Tomohiro; Okamoto, Daisuke; Taketomi, Akinobu; Shirabe, Ken; Honda, Hiroshi

2011-01-01

Purpose: To evaluate the characteristics of hepatocellular carcinomas (HCCs) with marginal superparamagnetic iron oxide (SPIO) uptake on T2*-weighted MRI. Materials and methods: The study group consisted of 73 patients with 83 surgically resected HCCs. Preoperative SPIO-enhanced MRI studies were retrospectively reviewed. Marginal SPIO uptake was considered positive if a rim-like or band-like low intensity area was present on SPIO-enhanced T2*-weighted images. The prevalence of marginal SPIO uptake was evaluated. Pathological specimens with hematoxylin and eosin staining and immunohistochemical staining of CD68 were reviewed in HCCs with marginal SPIO uptake and 33 HCCs without marginal SPIO uptake (control group). Results: Ten of 83 (12%) HCCs showed marginal SPIO uptake. All HCCs were hypervascular, and only one nodule showed a nodule-in-nodule appearance on imaging findings. The pathology specimens suggested possible causes of marginal SPIO uptake, including marginal macrophage infiltration in moderately or poorly differentiated HCC (n = 4), residual normal hepatic tissue at the marginal area of confluent multinodular or single nodular with extranodular growth type HCC (n = 3), and a well-differentiated HCC component in nodule-in-nodule type HCC (n = 3). Marginal macrophage infiltration was not seen in the control group. Conclusion: SPIO-enhanced MRI may be able to demonstrate marginal macrophage infiltration in HCC.

Effect of surface charge and agglomerate degree of magnetic iron oxide nanoparticles on KB cellular uptake in vitro.

Science.gov (United States)

Ge, Yuqing; Zhang, Yu; Xia, Jingguang; Ma, Ming; He, Shiying; Nie, Fang; Gu, Ning

2009-10-15

We synthesized three types of magnetic iron oxide nanoparticles (MNPs), which were meso-2,3-dimercaptosuccinic acid (DMSA) coated MNPs (DMSA@MNPs, 17.3+/-4.8 nm, negative charge), chitosan (CS) coated MNPs (CS@MNPs, 16.5+/-6.1 nm, positive charge) and magnetic nanoparticles agglomerates, formed by electronic aggregation between DMSA@MNPs and CS (CS-DMSA@MNPs, 85.7+/-72.9 nm, positive charge) respectively. The interactions of these MNPs with Oral Squamous Carcinoma Cell KB were investigated. The results showed that cellular uptakes of MNPs were on the dependence of incubation time, nanoparticles concentration and nanoparticles properties such as surface charge, size, etc. The cellular uptake was enhanced with the increase of incubation time and nanoparticles concentration. Although all MNPs could enter to cells, we observed apparent differences in the magnitude of nanoparticles uptaken. The cellular uptake of CS-DMSA@MNPs by KB cells was the highest and that of DMSA@MNPs was the lowest among the three types of MNPs. The same conclusions were drawn via the reduction of water proton relaxation times T(2)(*), resulting from the different iron load of labeled cells using a 1.5T clinical MR imager. The finding of this study will have implications in the chemical design of nanomaterials for biomedical applications.

The use of pulsed magnetic fields to increase the uptake of iron oxide nanoparticles by living cells

Czech Academy of Sciences Publication Activity Database

Uzhytchak, Mariia; Lynnyková, Anna; Zablotskyy, Vitaliy A.; Dempsey, N.M.; Dias, A.L.; Bonfim, M.; Lunova, Mariia; Jirsa, M.; Kubinová, Šárka; Lunov, Oleg; Dejneka, Alexandr

2017-01-01

Roč. 111, č. 24 (2017), s. 1-5, č. článku 243703. ISSN 0003-6951 Grant - others:AV ČR(CZ) Fellowship J. E. Purkyně Institutional support: RVO:68378271 Keywords : pulsed magnetic fields * increase the uptake * iron oxide * living cells Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.411, year: 2016

Cadmium uptake by and translocation within rice (oryza sativa l.) seedlings as affected by iron plaque and Fe/sub 2/O/sub 3/

International Nuclear Information System (INIS)

Lai, Y.; Xu, B.O.; Mou, S.

2012-01-01

A hydroponics culture experiment was carried out to investigate the effect of iron plaque and/or Fe/sub 2/O/sub 3/ on Cadmium (Cd) uptake by and translocation within rice seedlings. Uniform rice seedlings grown in nutrient solution for two weeks were selected and transferred to nutrient solution containing ferrous iron (Fe/sup 2+/) (30 mg/L) for 24 h to induce the formation of iron plaque on the root surface. Then rice seedlings were exposed to different level of Cd (1.0 mg/L and 0.1 mg/L), and simultaneously Fe/sub 2/O/sub 3/ was added into hydroponic system for three days. At harvest Cd content in dithionite-citrate-bicarbonate (DCB) extracts, roots and shoots were determined. The results of this study showed that iron plaque could sequester more Cd on root surfaces of rice seedlings, however, Fe/sub 2/O/sub 3/ reduced Cd adsorbed on root surfaces. Both of iron plaque and/or Fe/sub 2/O/sub 3/ did not block Cd uptake by and translocation within rice seedlings. Although iron plaque could alleviate Cd toxicity to rice seedlings under low concentration of Cd (0.1 mg/L), the root tissue played more important role in reducing Cd translocation into shoot. And the long period experiment of hydroponic and soil culture was still needed to verify the potential effect of iron plaque and/or Fe/sub 2/O/sub 3/ on alleviating Cd toxicity to rice seedlings. (author)

Influence of iron plaque on uptake and accumulation of Cd by rice (Oryza sativa L.) seedlings grown in soil.

Science.gov (United States)

Liu, Houjun; Zhang, Junling; Christie, Peter; Zhang, Fusuo

2008-05-15

Iron plaque is ubiquitously formed on the root surfaces of rice. However, little is known about the role of iron plaque in Cd movement from soil to the plant aboveground parts. A pot experiment was conducted to investigate the influence of iron plaque in Cd uptake and accumulation by rice seedlings in soil. Rice seedlings were pre-cultivated in solution culture for 16 days. Two seedlings were transplanted in a nylon bag containing no substrate but surrounded by soil amended with Fe and Cd combined at rates of 0, 1, or 2 g Fe kg(-1) and 0, 2.0, or 10 mg Cd kg(-1) soil. Fe was added to induce different amounts of iron plaque, and Cd to simulate Cd-polluted soils. Plants were grown for a further 43 days and then harvested. The length of the longest leaf and SPAD values of the newly mature leaves were measured during plant growth. Fe and Cd concentrations were determined in dithionite-citrate-bicarbonate (DCB) soil extracts and in plant roots and shoots. Shoot and root dry weights were significantly affected by Fe supply level but not by added Cd. Root dry weight declined with increasing Fe supply but shoot dry weight decreased at 2 g Fe kg(-1) and increased at 1 g Fe kg(-1) (except at 2 mg Cd kg(-1)). The length of the longest leaf and SPAD values of the newly mature leaves were significantly affected by plant growth stage and added Fe and Cd. Fe tended to diminish the negative effect of Cd on these two parameters. Cd concentrations in DCB extracts increased with increasing Cd and Fe supply. In contrast, external Fe supply markedly reduced shoot and root Cd concentrations and there was generally no significant difference between the two Fe supply levels. Shoot and root Cd concentrations increased with increasing Cd addition. Root Cd concentrations were negatively correlated with root Fe concentrations. The proportion of Cd in DCB extracts was significantly lower than in roots or shoots. The results indicate that enhanced Fe uptake by plants can diminish the negative

Response of the marine diatom Thalassiosira weissflogii to iron stress

International Nuclear Information System (INIS)

Harrison, G.I.; Morel, F.M.M.

1986-01-01

The coastal diatom Thalassiosira weissflogii responds to iron limitation with decreasing growth rate, decreasing quotas of cellular iron, and increasing rates of maximum short term uptake. Growth response to steady iron limitation can be modeled according to the equations of Droop and Monod. The cellular iron quota varies from about 2 to 25 x 10 -1 mol iron per liter-cell with increasing iron; the half-saturation constant for growth, Kμ, is 1.1 x 10 -21 M (free ferric ion). In contrast, the half-saturation constant for 59 I iron uptake, K/sub rho/ is about 3 x 10 -19 M; the maximum iron uptake rate (rho/sub max/) is increased several-fold under iron limitation, resulting in a potential short term uptake rate that is a few hundred times the steady state rate. At a fixed concentration of free manganese ion, the cellular manganese quota is increased several-fold in iron-limited cultures compared to iron-sufficient cultures

Sorptive Uptake Studies of an Aryl-Arsenical with Iron Oxide Composites on an Activated Carbon Support

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Jae H. Kwon

2014-03-01

Full Text Available Sorption uptake kinetics and equilibrium studies for 4-hydroxy-3-nitrobenzene arsonic acid (roxarsone was evaluated with synthetic magnetite (Mag-P, commercial magnetite (Mag-C, magnetite 10%, 19%, and 32% composite material (CM-10, -19, -32 that contains granular activated carbon (GAC, and synthetic goethite at pH 7.00 in water at 21 °C for 24 h. GAC showed the highest sorptive removal of roxarsone and the relative uptake for each sorbent material with roxarsone are listed in descending order as follows: GAC (471 mg/g > goethite (418 mg/g > CM-10 (377 mg/g CM-19 (254 mg/g > CM-32 (227 mg/g > Mag-P (132 mg/g > Mag-C (29.5 mg/g. The As (V moiety of roxarsone is adsorbed onto the surface of the iron oxide/oxyhydrate and is inferred as inner-sphere surface complexes; monodentate-mononuclear, bidentate-mononuclear, and bidentate-binuclear depending on the protolytic speciation of roxarsone. The phenyl ring of roxarsone provides the primary driving force for the sorptive interaction with the graphene surface of GAC and its composites. Thus, magnetite composites are proposed as multi-purpose adsorbents for the co-removal of inorganic and organic arsenicals due to the presence of graphenic and iron oxide active adsorption sites.

Regulatory mechanisms for iron transport across the blood-brain barrier.

Science.gov (United States)

Duck, Kari A; Simpson, Ian A; Connor, James R

2017-12-09

Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field. Copyright © 2017 Elsevier Inc. All rights reserved.

Intestinal Iron Homeostasis and Colon Tumorigenesis

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Yatrik M. Shah

2013-06-01

Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

Phytotoxicity and uptake of nanoscale zero-valent iron (nZVI) by two plant species

Energy Technology Data Exchange (ETDEWEB)

Ma, Xingmao, E-mail: ma@engr.siu.edu [Civil and Environmental Engineering, Southern Illinois University Carbondale, IL 62901 (United States); Gurung, Arun [Civil and Environmental Engineering, Southern Illinois University Carbondale, IL 62901 (United States); Deng, Yang [Earth and Environmental Studies, Montclair State University, NJ 07403 (United States)

2013-01-15

Use of nano-scale zero valent iron (nZVI) for the treatment of various environmental pollutants has been proven successful. However, large scale introduction of engineered nanomaterials such as nZVI into the environment has recently attracted serious concerns. There is an urgent need to investigate the environmental fate and impact of nZVI due to the scope of its application. The goal of this study was to evaluate the toxicity and accumulation of bare nZVI by two commonly encountered plant species: cattail (Typha latifolia) and hybrid poplars (Populous deltoids × Populous nigra). Plant seedlings were grown hydroponically in a greenhouse and dosed with different concentrations of nZVI (0–1000 mg/L) for four weeks. The nZVI exhibited strong toxic effect on Typha at higher concentrations (> 200 mg/L) but enhanced plant growth at lower concentrations. nZVI also significantly reduced the transpiration and growth of hybrid poplars at higher concentrations. Microscopic images indicated that large amount of nZVI coated on plant root surface as irregular aggregates and some nZVI penetrated into several layers of epidermal cells. Transmission electron microscope (TEM) and scanning transmission electron microscope (STEM) confirmed the internalization of nZVI by poplar root cells but similar internalization was not observed for Typha root cells. The upward transport to shoots was minimal for both plant species. - Highlights: ► nZVI may exert phytotoxic effects on plants at concentrations (> 200 mg/L) often encountered in site remediation practices. ► nZVI deposits on plant root surface as aggregates and some could internalize in plant root cells. ► Plant uptake and accumulation of nZVI are plant species-dependent. ► Upward transport from roots to shoots was not observed.

Uptake and Translocation of Iron by Native Tree Species In A Constructed Wetland Treating Landfill Leachates

OpenAIRE

A. Snow; Abdel E. Ghaly; R. Cote; A. M. Snow

2008-01-01

A surface flow wetland was constructed in the Burnside Industrial Park, Dartmouth, Nova Scotia, to treat stormwater runoff from the surrounding watersheds which are comprised primarily of commercial properties and two former landfills. The objectives of this study were: (a) to compare the uptake of iron by red maple, white birch and red spruce trees growing under flooded soil conditions in the constructed wetland and well drained soil conditions in a nearby reference site, (b) to evaluate the...

Enterobactin-mediated iron transport in Pseudomonas aeruginosa.

Science.gov (United States)

Poole, K; Young, L; Neshat, S

1990-01-01

A pyoverdine-deficient strain of Pseudomonas aeruginosa was unable to grow in an iron-deficient minimal medium in the presence of the nonmetabolizable iron chelator ethylene diamine-di(omega-hydroxyphenol acetic acid) (EDDHA), although addition of enterobactin to EDDHA-containing minimal media did restore growth of the pyoverdine-deficient P. aeruginosa. Consistent with the apparent ability of enterobactin to provide iron to P. aeruginosa, enterobactin-dependent 55Fe3+ uptake was observed in cells of P. aeruginosa previously grown in an iron-deficient medium containing enterobactin (or enterobactin-containing Escherichia coli culture supernatant). This uptake was energy dependent, was observable at low concentrations (60 nM) of FeCl3, and was absent in cells cultured without enterobactin. A novel protein with a molecular weight of approximately 80,000 was identified in the outer membranes of cells grown in iron-deficient minimal medium containing enterobactin, concomitant with the induction of enterobactin-dependent iron uptake. A Tn501 insertion mutant lacking this protein was isolated and shown to be deficient in enterobactin-mediated iron transport at 60 nM FeCl3, although it still exhibited enterobactin-dependent growth in iron-deficient medium containing EDDHA. It was subsequently observed that the mutant was, however, capable of enterobactin-mediated iron transport at much higher concentrations (600 nM) of FeCl3. Indeed, enterobactin-dependent iron uptake at this concentration of iron was observed in both the mutant and parent strains irrespective of whether they had been cultured in the presence of enterobactin.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:2174865

Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles.

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Arnaud Beduneau

Full Text Available BACKGROUND: We posit that the same mononuclear phagocytes (MP that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP and tissue delivery. METHODS: Monocytes and monocyte-derived macrophages (MDM were used as vehicles of superparamagnetic iron oxide (SPIO NP and immunoglobulin (IgG or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake into monocytes and MDM investigated related to size, time, temperature, concentration, and coatings. SPIO and IgG SPIO were infused intravenously into naïve mice. T(2 measures using magnetic resonance imaging (MRI were used to monitor tissue distribution in animals. RESULTS: Oxidation of dextran on the SPIO surface generated reactive aldehyde groups and permitted covalent linkage to amino groups of murine and human IgG and F(ab'(2 fragments and for Alexa Fluor(R 488 hydroxylamine to form a Schiff base. This labile intermediate was immediately reduced with sodium cyanoborohydride in order to stabilize the NP conjugate. Optical density measurements of the oxidized IgG, F(ab'(2, and/or Alexa Fluor(R 488 SPIO demonstrated approximately 50% coupling yield. IgG-SPIO was found stable at 4 degrees C for a period of 1 month during which size and polydispersity index varied little from 175 nm and 200 nm, respectively. In vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold less. No changes in cell viability were noted for the SPIO-containing monocytes and MDM. Cell morphology was not changed as observed by transmission electron microscopy. Compared to unconjugated

Building a Conceptual Framework to Study the Effect of HIV Stigma-Reduction Intervention Strategies on HIV Test Uptake: A Scoping Review.

Science.gov (United States)

Thapa, Subash; Hannes, Karin; Cargo, Margaret; Buve, Anne; Aro, Arja R; Mathei, Catharina

A scoping review of grey and peer-reviewed literature was conducted to develop a conceptual framework to illustrate mechanisms involved in reducing HIV stigma and increasing HIV test uptake. We followed a three-step approach to exploring the literature: developing concepts, organizing and categorizing concepts, and synthesizing concepts into a framework. The framework contains four types of intervention strategies: awareness creation, influencing normative behavior, providing support, and developing regulatory laws. The awareness creation strategy generally improves knowledge and the influencing normative behavior strategy changes stigmatizing attitudes and behaviors, and subsequently, increases HIV test uptake. Providing support and development of regulatory law strategies changes actual stigmatizing behaviors of the people, and subsequently, increases HIV test uptake. The framework further outlines that the mechanisms described are influenced by the interaction of various social-contextual and individual factors. The framework sheds new light on the effects of HIV stigma-reduction intervention strategies and HIV test uptake. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Iron uptake and transport at the blood-brain barrier

DEFF Research Database (Denmark)

Larsen, Annette Burkhart; Thomsen, Louiza Bohn; Moos, Torben

The mechanism by which iron is transported across the blood-brain barrier (BBB) remains controversial, and in this study we aimed to further clarify mechanisms by which iron is transported into the brain. We analyzed and compared the mRNA and protein expression of a variety of proteins involved...... in the transport of iron (transferrin receptor, divalent metal transporter I (DMT1), steap 2, steap 3, ceruloplasmin, hephaestin and ferroportin) in both primary rat brain capillary endothelial cells (BCEC) and immortalized rat brain capillary endothelial cell line (RBE4) grown in co-culture with defined polarity....... The mRNA expression of the iron-related molecules was also investigated in isolated brain capillaries from iron deficiency, iron reversible and normal rats. We also performed iron transport studies to analyze the routes by which iron is transported through the brain capillary endothelial cells: i) We...

The Bradyrhizobium japonicum Ferrous Iron Transporter FeoAB Is Required for Ferric Iron Utilization in Free Living Aerobic Cells and for Symbiosis.

Science.gov (United States)

Sankari, Siva; O'Brian, Mark R

2016-07-22

The bacterium Bradyrhizobium japonicum USDA110 does not synthesize siderophores for iron utilization in aerobic environments, and the mechanism of iron uptake within symbiotic soybean root nodules is unknown. An mbfA bfr double mutant defective in iron export and storage activities cannot grow aerobically in very high iron medium. Here, we found that this phenotype was suppressed by loss of function mutations in the feoAB operon encoding ferrous (Fe(2+)) iron uptake proteins. Expression of the feoAB operon genes was elevated under iron limitation, but mutants defective in either gene were unable to grow aerobically over a wide external ferric (Fe(3+)) iron (FeCl3) concentration range. Thus, FeoAB accommodates iron acquisition under iron limited and iron replete conditions. Incorporation of radiolabel from either (55)Fe(2+) or (59)Fe(3+) into cells was severely defective in the feoA and feoB strains, suggesting Fe(3+) reduction to Fe(2+) prior to traversal across the cytoplasmic membrane by FeoAB. The feoA or feoB deletion strains elicited small, ineffective nodules on soybean roots, containing few bacteria and lacking nitrogen fixation activity. A feoA(E40K) mutant contained partial iron uptake activity in culture that supported normal growth and established an effective symbiosis. The feoA(E40K) strain had partial iron uptake activity in situ within nodules and in isolated cells, indicating that FeoAB is the iron transporter in symbiosis. We conclude that FeoAB supports iron acquisition under limited conditions of soil and in the iron-rich environment of a symbiotic nodule. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

Energy Technology Data Exchange (ETDEWEB)

Leenders, K L [Paul Scherrer Inst., Villigen (Switzerland); [Neurology Dept., Univ. Hospital, Zuerich (Switzerland); Antonini, A; Schwarzbach, R; Smith-Jones, P; Reist, H [Paul Scherrer Inst., Villigen (Switzerland); Youdim, M [Pharmacology Dept., Technion, Haifa (Israel); Henn, V [Neurology Dept., Univ. Hospital, Zuerich (Switzerland)

1994-12-31

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson`s disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author).

Blood to brain iron uptake in one Rhesus monkey using [Fe-52]-citrate and positron emission tomography (PET): influence of haloperidol

International Nuclear Information System (INIS)

Leenders, K.L.; Antonini, A.; Schwarzbach, R.; Smith-Jones, P.; Reist, H.; Youdim, M.; Henn, V.

1994-01-01

Iron is highly concentrated in the basal ganglia of the brain. The involvement of cerebral iron and its handling systems in neurodegenerative brain diseases like Parkinson's disease and tardive dyskinesia is currently under close investigation. There is evidence from animal studies that neuroleptics can increase iron uptake into brain. This effect appeared to be due to alteration of blood-brain barrier transport by the neuroleptics, particularly chlorpromazine and haloperidol, but not clozapine. We have investigated one Rhesus monkey using positron emission tomography (PET) and [Fe-52]-citrate before and during haloperidol administration. After drug withdrawal during a period of 1.5 year the investigation procedure was repeated. The results show that in the investigated monkey haloperidol induces a reversible marked increase of iron transport across the blood brain barrier concomitant with a large increase in elimination rate of the tracer from the blood. (author)

Performance of Iron Plaque of Wetland Plants for Regulating Iron, Manganese, and Phosphorus from Agricultural Drainage Water

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Xueying Jia

2018-01-01

Full Text Available Agricultural drainage water continues to impact watersheds and their receiving water bodies. One approach to mitigate this problem is to use surrounding natural wetlands. Our objectives were to determine the effect of iron (Fe-rich groundwater on phosphorus (P removal and nutrient absorption by the utilization of the iron plaque on the root surface of Glyceria spiculosa (Fr. Schmidt. Rosh. The experiment was comprised of two main factors with three regimes: Fe2+ (0, 1, 20, 100, 500 mg·L−1 and P (0.01, 0.1, 0.5 mg·L−1. The deposition and structure of iron plaque was examined through a scanning electron microscope and energy-dispersive X-ray analyzer. Iron could, however, also impose toxic effects on the biota. We therefore provide the scanning electron microscopy (SEM on iron plaques, showing the essential elements were iron (Fe, oxygen (O, aluminum (Al, manganese (Mn, P, and sulphur (S. Results showed that (1 Iron plaque increased with increasing Fe2+ supply, and P-deficiency promoted its formation; (2 Depending on the amount of iron plaque on roots, nutrient uptake was enhanced at low levels, but at higher levels, it inhibited element accumulation and translocation; (3 The absorption of manganese was particularly affected by iron plague, which also enhanced phosphorus uptake until the external iron concentration exceeded 100 mg·L−1. Therefore, the presence of iron plaque on the root surface would increase the uptake of P, which depends on the concentration of iron-rich groundwater.

Effects of Iron-Oxide Nanoparticle Surface Chemistry on Uptake Kinetics and Cytotoxicity in CHO-K1 Cells

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Camille C. Hanot

2015-12-01

Full Text Available Superparamagnetic iron-oxide nanoparticles (SPIONs show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells. We evaluated the effect of particle diameter (50 and 100 nm and polyethylene glycol (PEG chain length (2k, 5k and 20k Da on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and sulforhodamine B (SRB assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS. Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications.

A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast.

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Javier Encinar del Dedo

2015-03-01

Full Text Available Iron is an essential cofactor, but it is also toxic at high levels. In Schizosaccharomyces pombe, the sensor glutaredoxin Grx4 guides the activity of the repressors Php4 and Fep1 to mediate a complex transcriptional response to iron deprivation: activation of Php4 and inactivation of Fep1 leads to inhibition of iron usage/storage, and to promotion of iron import, respectively. However, the molecular events ruling the activity of this double-branched pathway remained elusive. We show here that Grx4 incorporates a glutathione-containing iron-sulfur cluster, alone or forming a heterodimer with the BolA-like protein Fra2. Our genetic study demonstrates that Grx4-Fra2, but not Fep1 nor Php4, participates not only in iron starvation signaling but also in iron-related aerobic metabolism. Iron-containing Grx4 binds and inactivates the Php4 repressor; upon iron deprivation, the cluster in Grx4 is probably disassembled, the proteins dissociate, and Php4 accumulates at the nucleus and represses iron consumption genes. Fep1 is also an iron-containing protein, and the tightly bound iron is required for transcriptional repression. Our data suggest that the cluster-containing Grx4-Fra2 heterodimer constitutively binds to Fep1, and upon iron deprivation the disassembly of the iron cluster between Grx4 and Fra2 promotes reverse metal transfer from Fep1 to Grx4-Fra2, and de-repression of iron-import genes. Our genetic and biochemical study demonstrates that the glutaredoxin Grx4 independently governs the Php4 and Fep1 repressors through metal transfer. Whereas iron loss from Grx4 seems to be sufficient to release Php4 and allow its nuclear accumulation, total or partial disassembly of the Grx4-Fra2 cluster actively participates in iron-containing Fep1 activation by sequestering its iron and decreasing its interaction with promoters.

Hunger for iron: the alternative siderophore iron scavenging systems in highly virulent Yersinia.

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Alexander eRakin

2012-11-01

Full Text Available Low molecular weight siderophores are used by many living organisms to scavenge scarcely available ferric iron. Presence of at least a single siderophore-based iron acquisition system is usually acknowledged as a virulence-associated trait and a prerequisite to become an efficient and successful pathogen. Currently it is assumed that yersiniabactin (Ybt is the solely functional endogenous siderophore iron uptake system in highly virulent Yersinia (Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica biotype 1B. Genes responsible for biosynthesis, transport and regulation of the yersiniabactin (ybt production are clustered on a mobile genetic element, the High Pathogenicity Island (HPI that is responsible for broad dissemination of the ybt genes in Enterobacteriaceae. However, the ybt gene cluster is absent from nearly half of Y. pseudotuberculosis O3 isolates and epidemic Y. pseudotuberculosis O1 isolates responsible for the Far East Scarlet-like Fever. Several potential siderophore-mediated iron uptake gene clusters are documented in Yersinia genomes, however neither of them have been proven to be functional. It has been suggested that at least two siderophores alternative to Ybt may operate in the highly virulent Yersinia pestis / Y. pseudotuberculosis group, and are referred to as pseudochelin (Pch and yersiniachelin (Ych. Furthermore, most sporadic Y. pseudotuberculosis O1 strains possess gene clusters encoding all three iron scavenging systems. Thus, the Ybt system appears not to be the sole endogenous siderophore iron uptake system in the highly virulent yersiniae and may be efficiently substituted and / or supplemented by alternative iron scavenging systems.

Hepatic uptake of technetium-99m diphosphonate in thalassemia major

International Nuclear Information System (INIS)

Levy, H.M.; Smith, R.

1986-01-01

Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions

Enhanced Iron and Selenium Uptake in Plants by Volatile Emissions of Bacillus amyloliquefaciens (BF06

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Jianfei Wang

2017-01-01

Full Text Available Volatile organic compounds (VOCs released by plant growth-promoting rhizobacteria (PGPR are involved in promoting growth and triggering systemic resistance (ISR in plants. Importantly, the release of VOCs by some PGPR strains confers improved plant uptake of nutrient elements from the soil. However, the underlying mechanisms of VOCs-regulated nutrient acquisition remain elusive. In this study, VOCs were extracted and identified from Bacillus amyloliquefaciens (strain BF06 using gas chromatography–mass spectrometry (GC–MS. BF06 VOCs exposure significantly promoted the growth and photosynthesis of Arabidopsis plants. To explore how microbial VOCs stimulate growth in plants, gene expression profiles of Arabidopsis seedlings exposed to BF06 VOCs were examined using transcriptomic analyses. In screening differentially expressed genes (DEGs, most upregulated DEGs were found to be related to amino acid transport, iron (Fe uptake and homeostasis, and sulfate transport. Furthermore, BF06 VOCs significantly enhanced Fe absorption in plants under Fe-limited conditions. However, when nitric oxide (NO synthesis was inhibited, BF06 VOCs exposure could not substantially augment Fe acquisition in plants under alkaline stress, indicating that VOCs-mediated plant uptake of Fe was required for induction of root NO accumulation. In addition, BF06 VOCs exposure led to a marked increase in some genes encoding for sulfate transporters, and further increased Se accumulation in plants. Intriguingly, BF06 VOCs exposure failed to increase Se uptake in sultr1;2 mutants, which may indicate that high-level transcription of these sulfate transporters induced by BF06 VOCs was essential for enhancing Se absorption by plants. Taken together, our results demonstrated the potential of VOCs released by this strain BF06 to increase Fe and Se uptake in plants.

Iron

DEFF Research Database (Denmark)

Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

2014-01-01

and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...... of transcription factors, activation of the mitochondrial apoptotic machinery or of other cell death mechanisms. The pro-inflammatory cytokine IL-1β facilitates divalent metal transporter 1 (DMT1)-induced β-cell iron uptake and consequently ROS formation and apoptosis, and we propose that this mechanism provides...

Shigella Iron Acquisition Systems and their Regulation.

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Wei, Yahan; Murphy, Erin R

2016-01-01

Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production.

Mammalian iron metabolism and its control by iron regulatory proteins☆

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Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

2013-01-01

Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

Iron transport and storage in the coccolithophore: Emiliania huxleyi.

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Hartnett, Andrej; Böttger, Lars H; Matzanke, Berthold F; Carrano, Carl J

2012-11-01

Iron is an essential element for all living organisms due to its ubiquitous role in redox and other enzymes, especially in the context of respiration and photosynthesis. The iron uptake and storage systems of terrestrial/higher plants are now reasonably well understood with two basic strategies for iron uptake being distinguished: strategy I plants use a mechanism involving soil acidification and induction of Fe(III)-chelate reductase (ferrireductase) and Fe(II) transporter proteins while strategy II plants have evolved sophisticated systems based on high-affinity, iron specific, binding compounds called phytosiderophores. In contrast, there is little knowledge about the corresponding systems in marine plant-like lineages. Herein we report a study of the iron uptake and storage mechanisms in the coccolithophore Emiliania huxleyi. Short term radio-iron uptake studies indicate that iron is taken up by Emiliania in a time and concentration dependent manner consistent with an active transport process. Based on inhibitor studies it appears that iron is taken up directly as Fe(iii). However if a reductive step is involved the Fe(II) must not be accessible to the external environment. Upon long term exposure to (57)Fe we have been able, using a combination of Mössbauer and XAS spectroscopies, to identify a single metabolite which displays spectral features similar to the phosphorus-rich mineral core of bacterial and plant ferritins.

The role of p97 in iron metabolism in human brain glioma cells

International Nuclear Information System (INIS)

Xia Chunlin; Chen Guiwen; Qian Zhongming

2000-01-01

Objective: To investigate the role of p97 (melanotransferrin) in iron uptake in human brain glioma cells . Methods: Human brain glioma cell lines, GBM and BT325 were incubated in the medium containing 59 Fe-Citrate. The cells were treated with phosphatidylinositol-phospholipase C (PI-PLC) and pronase. The iron uptake of the cells was expressed as relative iron uptake level according to the cpm measured by the gamma scintillation counter. Results: 59 Fe uptake of the cells was significantly declined with the certain concentration of PI-PCL. 59 Fe uptake of the cells treated with pronase tended to coincide with that of the cells treated without pronase in the increasing concentration of PI-PLC. Conclusion: p97 expresses a high level and plays an important role in iron uptake in human brain glioma cells

Transgenic petunia with the iron(III)-phytosiderophore transporter gene acquires tolerance to iron deficiency in alkaline environments.

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Murata, Yoshiko; Itoh, Yoshiyuki; Iwashita, Takashi; Namba, Kosuke

2015-01-01

Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III) to iron(II) and the uptake of iron(II) by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III). Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III)-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III)-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III)-2'-deoxymugineic acid complex, free 2'-deoxymugineic acid and its iron(III) complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III)-2'-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems to diverse

Transgenic petunia with the iron(III-phytosiderophore transporter gene acquires tolerance to iron deficiency in alkaline environments.

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Yoshiko Murata

Full Text Available Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III to iron(II and the uptake of iron(II by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III. Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III-2'-deoxymugineic acid complex, free 2'-deoxymugineic acid and its iron(III complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III-2'-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems

Subcellular Iron Localization Mechanisms in Plants

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Emre Aksoy

2017-12-01

Full Text Available The basic micro-nutrient element iron (Fe is present as a cofactor in the active sites of many metalloproteins with important roles in the plant. On the other hand, since it is excessively reactive, excess accumulation in the cell triggers the production of reactive oxygen species, leading to cell death. Therefore, iron homeostasis in the cell is very important for plant growth. Once uptake into the roots, iron is distributed to the subcellular compartments. Subcellular iron transport and hence cellular iron homeostasis is carried out through synchronous control of different membrane protein families. It has been discovered that expression levels of these membrane proteins increase under iron deficiency. Examination of the tasks and regulations of these carriers is very important in terms of understanding the iron intake and distribution mechanisms in plants. Therefore, in this review, the transporters responsible for the uptake of iron into the cell and its subcellular distribution between organelles will be discussed with an emphasis on the current developments about these transporters.

Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

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Dimitri Vanhecke

2017-11-01

Full Text Available Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line were incubated with gold (AuNPs and iron oxide nanoparticles (FeOxNPs either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

The quality of Metroxylon Sago sucker: morphology and uptake of manganese and iron

International Nuclear Information System (INIS)

Nashriyah Mat; Abdul Khalik Wood; Ramli Ishak

2001-01-01

Metroxylon sago or sagopalm is an important source of carbohydrate for the South East Asian countries, apart from rice. In Malaysia, wild sagopalm grows in Sarawak in its natural habitats, the coastal peat swamp. The quality of sucker growing vegetatively on sagopalm was studied at Sungai Talau experimental station, Dalat plantation and Oya/Mukah plantation in Sarawak. The coefficients of variability (C) and Index of similiarity (I) were calculated based on sucker morphology and uptake of manganese and iron, The matrix of hypothetical exact interpoint distances (Indices of Similarity and Dissimilarity) shows that sucker on matured sagopalm at Sungai Talam experimental station was a high quality, sucker on 5 years old sagopalm at Mukah sago plantation was approximately one-third as good, whereas sucker on 1.5 years old sagopalm at Oya/dalat sago plantation was of inferior quality. (Author)

Application of Circuit Simulation Method for Differential Modeling of TIM-2 Iron Uptake and Metabolism in Mouse Kidney Cells

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Zhijian eXie

2013-06-01

Full Text Available Circuit simulation is a powerful methodology to generate differential mathematical models. Due to its highly accurate modelling capability, circuit simulation can be used to investigate interactions between the parts and processes of a cellular system. Circuit simulation has become a core technology for the field of electrical engineering, but its application in biology has not yet been fully realized. As a case study for evaluating the more advanced features of a circuit simulation tool called Advanced Design System (ADS, we collected and modeled laboratory data for iron metabolism in mouse kidney cells for a H ferritin (HFt receptor, T cell immunoglobulin and mucin domain-2 (TIM-2. The internal controlling parameters of TIM-2 associated iron metabolism were extracted and the ratios of iron movement among cellular compartments were quantified by ADS. The differential model processed by circuit simulation demonstrated a capability to identify variables and predict outcomes that could not be readily measured by in vitro experiments. For example, an initial rate of uptake of iron-loaded HFt was 2.17 pmol per million cells. TIM-2 binding probability with iron-loaded HFt was 16.6%. An average of 8.5 minutes was required for the complex of TIM-2 and iron-loaded HFt to form an endosome. The endosome containing HFt lasted roughly 2 hours. At the end of endocytosis, about 28% HFt remained intact and the rest was degraded. Iron released from degraded HFt was in the labile iron pool (LIP and stimulated the generation of endogenous HFt for new storage. Both experimental data and the model showed that TIM-2 was not involved in the process of iron export. The extracted internal controlling parameters successfully captured the complexity of TIM-2 pathway and the use of circuit simulation-based modeling across a wider range of cellular systems is the next step for validating the significance and utility of this method.

Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms.

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Enculescu, Mihaela; Metzendorf, Christoph; Sparla, Richard; Hahnel, Maximilian; Bode, Johannes; Muckenthaler, Martina U; Legewie, Stefan

2017-01-01

Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms. At the systemic level, the iron-regulatory hormone hepcidin is released from the liver in response to these cues, binds to ferroportin and triggers its degradation. The relative importance of individual ferroportin control mechanisms and their interplay at the systemic level is incompletely understood. Here, we built a mathematical model of systemic iron regulation. It incorporates the dynamics of organ iron pools as well as regulation by the hepcidin/ferroportin system. We calibrated and validated the model with time-resolved measurements of iron responses in mice challenged with dietary iron overload and/or inflammation. The model demonstrates that inflammation mainly reduces the amount of iron in the blood stream by reducing intracellular ferroportin transcription, and not by hepcidin-dependent ferroportin protein destabilization. In contrast, ferroportin regulation by hepcidin is the predominant mechanism of iron homeostasis in response to changing iron diets for a big range of dietary iron contents. The model further reveals that additional homeostasis mechanisms must be taken into account at very high dietary iron levels, including the saturation of intestinal uptake of nutritional iron and the uptake of circulating, non-transferrin-bound iron, into liver. Taken together, our model quantitatively describes systemic iron metabolism and generated experimentally testable predictions for additional

Extraosseous radiotracer uptake on bone scan in beta-thalassemia: report of one case

International Nuclear Information System (INIS)

Guezguez, M.; Nouira, M.; Sfar, R.; Chatti, K.; Ben Fradj, M.; Ben Ali, K.; Ajmi, S.; Essabbah, H.; Zrour, S.

2009-01-01

Red blood cell transfusion, main therapeutic modality of beta-thalassemia, leads to iron overload which may perturb several metabolic ways. The aim of this paper is to illustrate the uptake abnormalities observed on bone scan of thalassaemic patients and to discuss mechanisms of extraosseous accumulation of the radiopharmaceutical in this pathology. We report a 16-year-old child suffering from beta-thalassemia major undergoing transfusion therapy. A bone scan was indicated to look for osseous infection. This study revealed a little skeletal uptake and abnormal liver, splenic and renal accumulation. A repeat bone scan, performed three weeks later showed a better skeletal uptake which enabled the discovery of focal abnormalities and made the diagnostic easier. The effect of iron overload on radiopharmaceuticals uptake in bone scan is known since 1975. Dissociation of 99m Tc from the carrier ligand due to the presence of iron excess seems the most plausible hypothesis. Free 99m Tc can be bound to other tissular substrates which can explain extraosseous uptake. The normally available pool for bone is reduced and then the skeletal uptake decreased. This report limits considerably the sensitivity of the bone scan. A well-led iron chelation and eventually the use of diuretic drug may guarantee a better quality of bone scan images. (authors)

Uptake, translocation and transformation of antimony in rice (Oryza sativa L.) seedlings

International Nuclear Information System (INIS)

Cai, Fei; Ren, Jinghua; Tao, Shu; Wang, Xilong

2016-01-01

Antimony (Sb), as a toxic metalloid, has been gaining increasing research concerns due mainly to its severe pollution in many places. Rice has been identified to be the dominant intake route of Sb by residents close to the Sb mining areas. A hydroponic experiment was conducted to investigate the difference in uptake, translocation and transformation of Sb in rice seedlings of four cultivars exposed to 0.2 or 1.0 mg/L of Sb(V). The results showed that mass concentration of iron plaque (mg/kg FW) formed at the root surfaces of cultivar N was the highest among all tested cultivars at both low and high exposure levels of Sb(V). The accumulated Sb concentration in iron plaque significantly increased with an increase in mass concentration of iron plaque formed at the rice root. The total amount of iron plaque (mg/pot) at rice root generally increased with increasing exposed Sb(V) concentration, which was closely associated with the increasing lipid peroxidation in roots. Concentration percentage of Sb in rice root significantly reduced as the corresponding value in the iron plaque increased, suggesting that iron plaque formation strongly suppressed uptake of Sb by rice root. Sb concentration in rice tissues followed an order: root > stem, leaf. The japonica rice (cultivars N and Z) exhibited a stronger translocation tendency of Sb from root to stem than indica hybrid rice (cultivars F and G). Translocation of Sb from root of cultivar F to its stem and leaf was sharply enhanced with increasing Sb exposure concentration. Sb(V) could be reduced to Sb(III) in rice tissues, especially in stems (10–26% of the total Sb). For the sake of food safety, the difference in uptake, translocation and transformation of Sb in rice species planted in Sb-contaminated soils should be taken into consideration. - Highlights: • Sb(V) caused lipid peroxidation and increased iron plaque formation at root surface. • The iron plaque may suppress uptake of Sb by rice. • Cultivars

Iron – a key nexus in the virulence of Aspergillus fumigatus

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Hubertus eHaas

2012-02-01

Full Text Available Iron is an essential but in excess toxic nutrient. Therefore, fungi evolved fine-tuned mechanisms for uptake and storage of iron, such as the production of siderophores (low-molecular mass iron-specific chelators. In Aspergillus fumigatus, iron starvation causes extensive transcriptional remodeling involving two central transcription factors, which are interconnected in a negative transcriptional feed-back loop: the GATA-factor SreA and the bZip-factor HapX. During iron sufficiency SreA represses iron uptake, including reductive iron assimilation and siderophore-mediated iron uptake, to avoid toxic effects. During iron starvation HapX represses iron-consuming pathways, including heme biosynthesis and respiration, to spare iron and activates synthesis of ribotoxin AspF1 and siderophores, the latter partly by ensuring supply of the precursor ornithine. In agreement with the expression pattern and mode of action, detrimental effects of inactivation of SreA and HapX are confined to growth during iron sufficiency and iron starvation, respectively. Deficiency in HapX, but not SreA, attenuates virulence of A. fumigatus in a murine model of aspergillosis, which underlines the crucial role of adaptation to iron limitation in virulence. Consistently, production of both extra- and intracellular siderophores is crucial for virulence of A. fumigatus. Recently, the sterol-regulatory element-binding protein SrbA was found to be essential for adaptation to iron starvation, thereby linking regulation of iron metabolism, ergosterol biosynthesis, azole drug resistance and hypoxia adaptation.

Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells.

Science.gov (United States)

Philpott, Caroline C; Ryu, Moon-Suhn; Frey, Avery; Patel, Sarju

2017-08-04

Eukaryotic cells contain hundreds of metalloproteins that are supported by intracellular systems coordinating the uptake and distribution of metal cofactors. Iron cofactors include heme, iron-sulfur clusters, and simple iron ions. Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperones in the cytosolic/nuclear compartment, binding iron at import and delivering it to enzymes, for storage (ferritin) and export (ferroportin). Ferritin iron is mobilized by autophagy through the cargo receptor, nuclear co-activator 4. The monothiol glutaredoxin Glrx3 and BolA2 function as a [2Fe-2S] chaperone complex. These proteins form a core system of cytosolic iron cofactor chaperones in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Two-Component Signaling System VgrRS Directly Senses Extracytoplasmic and Intracellular Iron to Control Bacterial Adaptation under Iron Depleted Stress.

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Li Wang

2016-12-01

Full Text Available Both iron starvation and excess are detrimental to cellular life, especially for animal and plant pathogens since they always live in iron-limited environments produced by host immune responses. However, how organisms sense and respond to iron is incompletely understood. Herein, we reveal that in the phytopathogenic bacterium Xanthomonas campestris pv. campestris, VgrS (also named ColS is a membrane-bound receptor histidine kinase that senses extracytoplasmic iron limitation in the periplasm, while its cognate response regulator, VgrR (ColR, detects intracellular iron excess. Under iron-depleted conditions, dissociation of Fe3+ from the periplasmic sensor region of VgrS activates the VgrS autophosphorylation and subsequent phosphotransfer to VgrR, an OmpR-family transcription factor that regulates bacterial responses to take up iron. VgrR-VgrS regulon and the consensus DNA binding motif of the transcription factor VgrR were dissected by comparative proteomic and ChIP-seq analyses, which revealed that in reacting to iron-depleted environments, VgrR directly or indirectly controls the expressions of hundreds of genes that are involved in various physiological cascades, especially those associated with iron-uptake. Among them, we demonstrated that the phosphorylated VgrR tightly represses the transcription of a special TonB-dependent receptor gene, tdvA. This regulation is a critical prerequisite for efficient iron uptake and bacterial virulence since activation of tdvA transcription is detrimental to these processes. When the intracellular iron accumulates, the VgrR-Fe2+ interaction dissociates not only the binding between VgrR and the tdvA promoter, but also the interaction between VgrR and VgrS. This relieves the repression in tdvA transcription to impede continuous iron uptake and avoids possible toxic effects of excessive iron accumulation. Our results revealed a signaling system that directly senses both extracytoplasmic and intracellular

Proteomic analysis of iron acquisition, metabolic and regulatory responses of Yersinia pestis to iron starvation

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Fleischmann Robert D

2010-01-01

Full Text Available Abstract Background The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C. Results Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis iron/siderophore acquisition systems (Ybt, Yfe, Yfu, Yiu and Hmu and a putative iron/chelate outer membrane receptor (Y0850 were increased in abundance in iron-starved cells. The iron-sulfur (Fe-S cluster assembly system Suf, adapted to oxidative stress and iron starvation in E. coli, was also more abundant, suggesting functional activity of Suf in Y. pestis under iron-limiting conditions. Metabolic and reactive oxygen-deactivating enzymes dependent on Fe-S clusters or other iron cofactors were decreased in abundance in iron-depleted cells. This data was consistent with lower activities of aconitase and catalase in iron-starved vs. iron-rich cells. In contrast, pyruvate oxidase B which metabolizes pyruvate via electron transfer to ubiquinone-8 for direct utilization in the respiratory chain was strongly increased in abundance and activity in iron-depleted cells. Conclusions Many protein abundance differences were indicative of the important regulatory role of the ferric uptake regulator Fur. Iron deficiency seems to result in a coordinated shift from iron-utilizing to iron-independent biochemical pathways in the cytoplasm of Y. pestis. With growth temperature as an additional variable in proteomic comparisons of the Y. pestis fractions (26°C and 37°C, there was

Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: In Vitro Cellular Uptake

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Min Wu

2017-12-01

Full Text Available Iron deficiency anemia is a common clinical consequence for people who suffer from chronic kidney disease, especially those requiring dialysis. Intravenous (IV iron therapy is a widely accepted safe and efficacious treatment for iron deficiency anemia. Numerous IV iron drugs have been approved by U.S. Food and Drug Administration (FDA, including a single generic product, sodium ferric gluconate complex in sucrose. In this study, we compared the cellular iron uptake profiles of the brand (Ferrlecit® and generic sodium ferric gluconate (SFG products. We used a colorimetric assay to examine the amount of iron uptake by three human macrophage cell lines. This is the first published study to provide a parallel evaluation of the cellular uptake of a brand and a generic IV iron drug in a mononuclear phagocyte system. The results showed no difference in iron uptake across all cell lines, tested doses, and time points. The matching iron uptake profiles of Ferrlecit® and its generic product support the FDA’s present position detailed in the draft guidance on development of SFG complex products that bioequivalence can be based on qualitative (Q1 and quantitative (Q2 formulation sameness, similar physiochemical characterization, and pharmacokinetic bioequivalence studies.

Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas.

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Sheo Shankar Pandey

2016-11-01

Full Text Available Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named Xanthomonas iron binding regulator of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc. Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon's involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in

Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas

Science.gov (United States)

Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

2016-01-01

Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named X anthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon’s involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in

Iron plaque formation on roots of different rice cultivars and the relation with lead uptake.

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Liu, Jianguo; Leng, Xuemei; Wang, Mingxin; Zhu, Zhongquan; Dai, Qinghua

2011-07-01

The relationships between lead (Pb) uptake and iron/manganese plaque formation on rice roots were investigated with three cultivars. The results showed that the rice cultivars with indica consanguinity were more sensitive to soil Pb stress than the cultivar with japonica consanguinity. Pb concentrations and distribution ratios in root tissues were in the order: Shanyou 63 > Yangdao 6 > Wuyunjing 7, but Pb and Fe concentrations and distribution ratios in the plaques showed a reverse order. Mn concentrations and distribution ratios in the plaques of Wuyunjing 7 were significantly higher (P rice root can provide a barrier to soil Pb stress. The plaque will increase sequestration of Pb on rice root surface and in the rhizosphere, providing a means of external exclusion of soil Pb to some extent. Copyright © 2011 Elsevier Inc. All rights reserved.

The influence of high iron diet on rat lung manganese absorption

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Thompson, Khristy; Molina, Ramon; Donaghey, Thomas; Brain, Joseph D.; Wessling-Resnick, Marianne

2006-01-01

Individuals chronically exposed to manganese are at high risk for neurotoxic effects of this metal. A primary route of exposure is through respiration, although little is known about pulmonary uptake of metals or factors that modify this process. High dietary iron levels inversely affect intestinal uptake of manganese, and a major goal of this study was to determine if dietary iron loading could increase lung non-heme iron levels and alter manganese absorption. Rats were fed a high iron (1% carbonyl iron) or control diet for 4 weeks. Lung non-heme iron levels increased ∼2-fold in rats fed the high iron diet. To determine if iron-loading affected manganese uptake, 54 Mn was administered by intratracheal (it) instillation or intravenous (iv) injection for pharmacokinetic studies. 54 Mn absorption from the lungs to the blood was lower in it-instilled rats fed the 1% carbonyl iron diet. Pharmacokinetics of iv-injected 54 Mn revealed that the isotope was cleared more rapidly from the blood of iron-loaded rats. In situ analysis of divalent metal transporter-1 (DMT1) expression in lung detected mRNA in airway epithelium and bronchus-associated lymphatic tissue (BALT). Staining of the latter was significantly reduced in rats fed the high iron diet. In situ analysis of transferrin receptor (TfR) mRNA showed staining in BALT alone. These data demonstrate that manganese absorption from the lungs to the blood can be modified by iron status and the route of administration

Mechanism of iron uptake by the pathogenic yeast, Candida albicans

International Nuclear Information System (INIS)

Ismail, A.

1986-01-01

C. albicans requires iron for growth and phenotypic development. When deprived of iron, mycelium and bud formation was suppressed. Survival of the organism was also reduced under iron-limiting conditions. The combination of elevated temperature and iron-deprivation further reduced phenotypic development and survival of the yeast. The combination of elevated temperature and iron starvation resulted in a decrease in both the growth rate and siderophore production. However, with time, the cells were able to show partial recovery in the growth rate which occurred concomitantly with an increase in siderophore production. In order for siderophores to be utilized, ferri-siderophore receptors must be produced. The receptor was shown to be located in the plasma membrane of the yeast. Scatchard analysis of the binding of ferri-siderophores to plasma membrane receptors showed an increase in receptor affinity and number of binding sites in iron-starved cells when compared to control cells. Autoradiograms of the 58 Fe-siderophore-protein complex following SDS-PAGE separation of candidal proteins revealed the presence of a ferri-siderophore receptor of approximately 10,000 daltons. C. albicans strains which lacked the ability to synthesize phenolate siderophore maintained a phenolate receptor and bound candidal phenolate siderophore better than non-candidal phenolate siderophores

Mechanism and developmental changes in iron transport across the blood-brain barrier.

Science.gov (United States)

Morgan, Evan H; Moos, Torben

2002-01-01

Transferrin and iron uptake by the brain were measured using [(59)Fe-(125)I]transferrin injected intravenously in rats aged from 15 days to 22 weeks. The values for both decreased with age. In rats aged 18 and 70 days the uptake was measured at short time intervals after the injection. When expressed as the volume of distribution (Vd), which represents the volume of plasma from which the transferrin and iron were derived, the results for iron were greater than those of transferrin as early as 7 min after injection and the difference increased rapidly with time, especially in the younger animals. A very similar time course was found for uptake by bone marrow (femurs) where iron uptake involves receptor-mediated endocytosis of Fe-transferrin, release of iron in the cell and recycling of apo-transferrin to the blood. It is concluded that, during transport of transferrin-bound plasma iron into the brain, a similar process occurs in brain capillary endothelial cells (BCECs) and that transcytosis of transferrin into the brain interstitium is only a minor pathway. Also, the high rate of iron transport into the brain in young animals, when iron requirements are high due to rapid growth of the brain, is a consequence of the level of expression and rate of recycling of transferrin receptors on BCECs. As the animal and brain mature both decrease. Copyright 2002 S. Karger AG, Basel

Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake

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Xiao Chen

2017-08-01

Full Text Available Background: Andrographolide (ADR, the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.

The importance of the stem cell marker prominin-1/CD133 in the uptake of transferrin and in iron metabolism in human colon cancer Caco-2 cells.

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Erika Bourseau-Guilmain

Full Text Available As the pentaspan stem cell marker CD133 was shown to bind cholesterol and to localize in plasma membrane protrusions, we investigated a possible function for CD133 in endocytosis. Using the CD133 siRNA knockdown strategy and non-differentiated human colon cancer Caco-2 cells that constitutively over-expressed CD133, we provide for the first time direct evidence for a role of CD133 in the intracellular accumulation of fluorescently labeled extracellular compounds. Assessed using AC133 monoclonal antibody, CD133 knockdown was shown to improve Alexa488-transferrin (Tf uptake in Caco-2 cells but had no impact on FITC-dextran or FITC-cholera-toxin. Absence of effect of the CD133 knockdown on Tf recycling established a role for CD133 in inhibiting Tf endocytosis rather than in stimulating Tf exocytosis. Use of previously identified inhibitors of known endocytic pathways and the positive impact of CD133 knockdown on cellular uptake of clathrin-endocytosed synthetic lipid nanocapsules supported that CD133 impact on endocytosis was primarily ascribed to the clathrin pathway. Also, cholesterol extraction with methyl-β-cyclodextrine up regulated Tf uptake at greater intensity in the CD133(high situation than in the CD133(low situation, thus suggesting a role for cholesterol in the inhibitory effect of CD133 on endocytosis. Interestingly, cell treatment with the AC133 antibody down regulated Tf uptake, thus demonstrating that direct extracellular binding to CD133 could affect endocytosis. Moreover, flow cytometry and confocal microscopy established that down regulation of CD133 improved the accessibility to the TfR from the extracellular space, providing a mechanism by which CD133 inhibited Tf uptake. As Tf is involved in supplying iron to the cell, effects of iron supplementation and deprivation on CD133/AC133 expression were investigated. Both demonstrated a dose-dependent down regulation here discussed to the light of transcriptional and post

Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors

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Peterson, K.M.; Alderete, J.F.

1984-08-01

Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites.

Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors

International Nuclear Information System (INIS)

Peterson, K.M.; Alderete, J.F.

1984-01-01

Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites

Plant mechanisms of siderophore-iron utilization

International Nuclear Information System (INIS)

Crowley, D.E.

1986-01-01

Mechanisms of siderophore iron-utilization by plants were examined to determine whether plants have direct mechanisms for acquiring iron from microbially-produced hydroxamate siderophores or simply take up inorganic iron in equilibrium with the chelate (shuttle mechanism). Experiments were designed to determine whether the monocot plant species, oat (Avena sativa L. cv. Victory) could acquire iron from ferrichrome under hydroponic conditions in which iron uptake was most likely to occur by direct use of the chelating agent. Ten-day-old iron-deficient seedlings, grown in aerated Hoagland's nutrient solution (minus iron) buffered at pH 7.4 with CaCO 3 , were placed in fresh nutrient solution containing 10/sup -7.4/M radioactive 55 FeCl 3 (23.7 mCi/mg) with the synthetic chelate, EDDHA (10π 5 M), ferrichrome (10 -5 M), or with no chelate. After 6 days, shoot content of 55 Fe in shoots of plants provided with ferrichrome was 100-fold greater than that in shoots of plants provided with EDDHA. Therefore iron uptake by oat under these conditions not only indicates direct use of ferrichrome, but also suggest that oat may be better able to acquire iron from siderophores than from synthetic chelates. One possible mechanism for direct use of chelating agents, may involve siderophore binding sites on the plasmalemma of root cortical cells where iron is split from the chelate by enzymatic reduction of ferric to ferrous iron. To demonstrate hypothesized siderophore binding sites on oat roots, experiments examined possible competition for presumed siderophore binding sites by an inert analog of ferrichrome constructed by irreversible chelation with chromium

Competitive advantage of diferric transferrin in delivering iron to reticulocytes.

Science.gov (United States)

Huebers, H A; Csiba, E; Huebers, E; Finch, C A

1983-01-01

Radioiron- and radioiodine-labeled forms of human diferric and monoferric transferrin and apotransferrin, isolated by preparative isoelectric focusing, were used to define transferrin-iron uptake by human reticulocytes. In mixtures of human diferric and monoferric transferrin, the diferric molecule had a constant 7-fold advantage in delivering iron to reticulocytes, as compared with the 2-fold advantage when single solutions of mono- and diferric transferrins were compared. This was shown to be due to competitive interaction in iron delivery, probably at a common membrane-receptor binding site for transferrin. Apotransferrin did not interfere with the iron-donating process and its limited cellular uptake was inhibited in noncompetitive fashion by diferric transferrin. PMID:6572005

Effects of Exogenous Gibberellic Acid3 on Iron and Manganese Plaque Amounts and Iron and Manganese Uptake in Rice

Science.gov (United States)

Guo, Yue; Zhu, Changhua; Gan, Lijun; Ng, Denny; Xia, Kai

2015-01-01

Gibberellins (GA) regulate various components of plant development. Iron and Mn plaque result from oxiding and hydroxiding Fe and Mn, respectively, on the roots of aquatic plant species such as rice (Oryza sativa L.). In this study, we found that exogenous gibberellic acid3 (GA3) spray decreased Fe plaque, but increased Mn plaque, with applications of Kimura B nutrient solution. Similar effects from GA3, leading to reduced Fe plaque and increased Mn plaque, were also found by scanning electron microscopy and energy dispersive X-ray spectrometric microanalysis. Reduced Fe plaque was observed after applying GA3 to the groups containing added Fe2+ (17 and 42 mg•L-1) and an increasing trend was detected in Mn plaques of the Mn2+ (34 and 84 mg•L-1) added treatments. In contrast, an inhibitor of GA3, uniconazole, reversed the effects of GA3. The uptake of Fe or Mn in rice plants was enhanced after GA3 application and Fe or Mn plaque production. Strong synergetic effects of GA3 application on Fe plaque production were detected. However, no synergetic effects on Mn plaque production were detected. PMID:25710173

Altered biodistribution of gallium-67 in a patient with multiple factors influencing iron-transport protein saturation

Energy Technology Data Exchange (ETDEWEB)

Choi, Jeon Young; Kim, Sang Eun; Lee, Kyung Han; Kim, Byung Tae [College of Medicine, Samsung Medical Center, Seoul (Korea, Republic of)

1998-01-01

We present a case of a young female patient with fulminant hepatitis who showed an altered biodistribution of Ga-67, after being scanned twice at 10 month intervals. On initial scan, uptake of Ga-67 was increased in the liver, kidneys, and skeletons. Increased hepatic Ga-67 uptake may be explained by increased transferrin unbound Ga-67 that was taken up by the inflamed liver. The saturation of iron-binding proteins due to multiple transfusions may lead to increased renal and skeletal Ga-67 uptake. On follow-up scan hepatic Ga-67 uptake was markedly increased. Also increased Ga-67 uptake in the axial skeleton and normalized renal uptake were shown. The findings were consistent with iron deficiency anemia. This case demonstrates altered Ga-67 biodistribution associated with multiple transfusions, fulminant hepatitis, and iron deficiency anemia.

Ferrokinetic studies in normal and iron deficiency anemic calves

International Nuclear Information System (INIS)

Moellerberg, L.; Ekman, L.; Jacobsson, S.-O.

1975-01-01

inetic studies were performed on control calves and on calves with experimentallally induced iron deficiency anemia, all 15 weeks old. The plasma iron clearance half time was about 4 times shorter in the experimental than in the control group. The low plasma iron concentration in the anemic calves was partially compensated by a more rapid plasma iron disappearance. Therefore the difference in the plasma iron turnover rate was reduced. The mean value of plasma iron renewal rate was about 3 times higher in the experimental than in the control group. The maximum uptake of injected 59 Fe into blood cells was reached 14 to 16 days after injection. The uptake of 59 Fe was about 10 % higher in the control than in the experimental group. Using the values from the ferrokinetietic study, the iron need for calves could be estimated. The requirement of iron to maintain a normal and constant Hb in a calf weighing 100 kg at a growth rate of 1 kg/daily was estimated as being 17.5 mg/day. Based on information in the literature and assuming a retention of dietary Fe of 25 %, the total daily iron need for such a calf gaining 1 kg/day would be 160-180 mg. (author)

Impairment of Interrelated Iron- and Copper Homeostatic Mechanisms in Brain Contributes to the Pathogenesis of Neurodegenerative Disorders

Science.gov (United States)

Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

2012-01-01

Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead to altered copper homeostasis in the brain. Similarly, changes in dietary copper affect the brain iron homeostasis. Moreover, the uptake routes of iron and copper overlap each other which affect the interplay between the concentrations of the two metals in the brain. The divalent metal transporter-1 (DMT1) is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake, and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells that express various transporters. PMID:23055972

Genomic Organization and Expression of Iron Metabolism Genes in the Emerging Pathogenic Mold Scedosporium apiospermum

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Yohann Le Govic

2018-04-01

Full Text Available The ubiquitous mold Scedosporium apiospermum is increasingly recognized as an emerging pathogen, especially among patients with underlying disorders such as immunodeficiency or cystic fibrosis (CF. Indeed, it ranks the second among the filamentous fungi colonizing the respiratory tract of CF patients. However, our knowledge about virulence factors of this fungus is still limited. The role of iron-uptake systems may be critical for establishment of Scedosporium infections, notably in the iron-rich environment of the CF lung. Two main strategies are employed by fungi to efficiently acquire iron from their host or from their ecological niche: siderophore production and reductive iron assimilation (RIA systems. The aim of this study was to assess the existence of orthologous genes involved in iron metabolism in the recently sequenced genome of S. apiospermum. At first, a tBLASTn analysis using A. fumigatus iron-related proteins as query revealed orthologs of almost all relevant loci in the S. apiospermum genome. Whereas the genes putatively involved in RIA were randomly distributed, siderophore biosynthesis and transport genes were organized in two clusters, each containing a non-ribosomal peptide synthetase (NRPS whose orthologs in A. fumigatus have been described to catalyze hydroxamate siderophore synthesis. Nevertheless, comparative genomic analysis of siderophore-related clusters showed greater similarity between S. apiospermum and phylogenetically close molds than with Aspergillus species. The expression level of these genes was then evaluated by exposing conidia to iron starvation and iron excess. The expression of several orthologs of A. fumigatus genes involved in siderophore-based iron uptake or RIA was significantly induced during iron starvation, and conversely repressed in iron excess conditions. Altogether, these results indicate that S. apiospermum possesses the genetic information required for efficient and competitive iron uptake

Using Perls Staining to Trace the Iron Uptake Pathway in Leaves of a Prunus Rootstock Treated with Iron Foliar Fertilizers.

Science.gov (United States)

Rios, Juan J; Carrasco-Gil, Sandra; Abadía, Anunciación; Abadía, Javier

2016-01-01

The aim of this study was to trace the Fe uptake pathway in leaves of Prunus rootstock (GF 677; Prunus dulcis × Prunus persica) plants treated with foliar Fe compounds using the Perls blue method, which detects labile Fe pools. Young expanded leaves of Fe-deficient plants grown in nutrient solution were treated with Fe-compounds using a brush. Iron compounds used were the ferrous salt FeSO4, the ferric salts Fe2(SO4)3 and FeCl3, and the chelate Fe(III)-EDTA, all of them at concentrations of 9 mM Fe. Leaf Fe concentration increases were measured at 30, 60, 90 min, and 24 h, and 70 μm-thick leaf transversal sections were obtained with a vibrating microtome and stained with Perls blue. In vitro results show that the Perls blue method is a good tool to trace the Fe uptake pathway in leaves when using Fe salts, but is not sensitive enough when using synthetic Fe(III)-chelates such as Fe(III)-EDTA and Fe(III)-IDHA. Foliar Fe fertilization increased leaf Fe concentrations with all Fe compounds used, with inorganic Fe salts causing larger leaf Fe concentration increases than Fe(III)-EDTA. Results show that Perls blue stain appeared within 30 min in the stomatal areas, indicating that Fe applied as inorganic salts was taken up rapidly via stomata. In the case of using FeSO4 a progression of the stain was seen with time toward vascular areas in the leaf blade and the central vein, whereas in the case of Fe(III) salts the stain mainly remained in the stomatal areas. Perls stain was never observed in the mesophyll areas, possibly due to the low concentration of labile Fe pools.

75 FR 79339 - Notice of Scope Rulings

Science.gov (United States)

2010-12-20

... Trade Administration, U.S. Department of Commerce, 14th Street and Constitution Avenue, NW., Washington... calendar quarter. Scope Rulings Completed Between April 1, 2010, and June 30, 2010: People's Republic of China A-570-502: Iron Construction Castings From the People's Republic of China Requestor: National...

Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells

International Nuclear Information System (INIS)

Martin, Amanda L.; Hickey, Jennifer L.; Ablack, Amber L.; Lewis, John D.; Luyt, Leonard G.; Gillies, Elizabeth R.

2010-01-01

The imaging of molecular markers associated with disease offers the possibility for earlier detection and improved treatment monitoring. Receptors for gastrin-releasing peptide are overexpressed on prostate cancer cells offering a promising imaging target, and analogs of bombesin, an amphibian tetradecapeptide have been previously demonstrated to target these receptors. Therefore, the pan-bombesin analog [β-Ala11, Phe13, Nle14]bombesin-(7-14) was conjugated through a linker to dye-functionalized superparamagnetic iron oxide nanoparticles for the development of a new potential magnetic resonance imaging probe. The peptide was conjugated via click chemistry, demonstrating a complementary alternative methodology to conventional peptide-nanoparticle conjugation strategies. The peptide-functionalized nanoparticles were then demonstrated to be selectively taken up by PC-3 prostate cancer cells relative to unfunctionalized nanoparticles and this uptake was inhibited by the presence of free peptide, confirming the specificity of the interaction. This study suggests that these nanoparticles have the potential to serve as magnetic resonance imaging probes for the detection of prostate cancer.

Iron plaque formation and morphoanatomy of roots from species of restinga subjected to excess iron.

Science.gov (United States)

Siqueira-Silva, Advanio Inácio; da Silva, Luzimar Campos; Azevedo, Aristéa Alves; Oliva, Marco Antonio

2012-04-01

The restingas, a sandy coastal plain ecosystem of Brazil, have received an additional amount of iron due to the activity of mining industries. The present study aims to characterize morphoanatomically and histochemically the iron plaque formation on roots of Ipomoea pes-caprae L. and Canavalia rosea DC, cultivated in hydroponic solution with and without excess iron. The iron plaque formation as well as changes in the external morphology of the lateral roots of both species were observed after the subjection to excess iron. Changes in the nutrient uptake, and in the organization and form of the pericycle and cortex cells were observed for both species. Scanning electron microscopy showed evident iron plaques on the whole surface of the root. The iron was histolocalized in all root tissues of both species. The species of restinga studied here formed iron plaque in their roots when exposed to excess of this element, which may compromise their development in environments polluted by particulated iron. Copyright © 2011 Elsevier Inc. All rights reserved.

Integrity of the iron transport process in mice with X-linked anaemia

International Nuclear Information System (INIS)

Thomson, A.B.R.; Valberg, L.S.

1975-01-01

The defect in iron (Fe) absorption in X-linked anaemia (sla) remains an enigma; absorption of a tracer dose of Fe is impaired in mice raised on an iron-containing cube diet but not in those raised on an iron-deficient diet. Because cobalt (Co) shares a similar intestinal transport pathway with Fe, a study was made of the effect of iron deficient diet on Co absorption. The duodenum of sla and genetically normal mice was perfused for 30 min with labelled solutions containing Co or Fe. Co uptake and transfer were similar in sla and normals fed cubes whereas Fe uptake and transfer were less in sla than in normals. The iron deficient diet caused an increase in the uptake and transfer of Co and Fe in sla and normals. When Co and Fe were perfused together in sla fed deficient diet, the uptake and transfer of each metal was less than when perfused alone. The distribution of Fe and Co in subcellular mucosal fractions was determined by a differential centrifugation technique. Deficient diet resulted in a directionally similar change in the subcellular distribution of Co and Fe in sla and normals. The increase in Co as well as Fe absorption in the sla on an iron deficient diet to the same high level found in genetically normal animals, and the inhibitory effect of each metal on the absorption of the other suggests that the absorption defect in sla is unlikely to be due to a primary defect in the function of the transport carrier. (author)

Effects of Chemical Applications to Metal Polluted Soils on Cadmium Uptake by Rice Plant

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Yoo J. H.

2013-04-01

Full Text Available Pot experiment using metal polluted soils was conducted to investigate the effects of lime, iron and sulfur on changes in Cd availability and uptake by rice plant. Drainage and irrigation of water were performed to develop redox changes like field cultivation. Iron chloride and sodium sulfate solutions were applied to the pots in the middle of growth period of rice plant. Reactive metal pool in heavily polluted soils was slightly decreased after treatments with lime, iron chloride, sodium sulfate and combination of these chemicals. However, cadmium uptake by rice plant was significantly different across the treatments and the extent of Cd pollution. For highly polluted soils, more Cd reduction was observed in iron chloride treatments. Cd content in polished rice for iron chloride and (iron chloride+organic matter treatments was only 16-23% and 25-37% compared to control and liming, respectively. Treatment of (iron chloride+sulfate rather increased Cd content in rice. For moderately polluted soils, Cd reduction rate was the order of (OM+iron chloride > iron chloride > lime. Other treatments including sulfate rather increased Cd content in rice maximum 3 times than control. It was proposed to determine the optimum application rate of iron for minimizing hazardous effect on rice plant.

Impact of Silver and Iron Nanoparticle Exposure on Cholesterol Uptake by Macrophages

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Jonathan H. Shannahan

2015-01-01

Full Text Available Macrophages are central to the development of atherosclerosis by absorbing lipids, promoting inflammation, and increasing plaque deposition. Nanoparticles (NPs are becoming increasingly common in biomedical applications thereby increasing exposure to the immune and vascular systems. This project investigated the influence of NPs on macrophage function and specifically cholesterol uptake. Macrophages were exposed to 20 nm silver NPs (AgNPs, 110 nm AgNPs, or 20 nm Fe3O4 NPs for 2 h and NP uptake, cytotoxicity, and subsequent uptake of fluorescently labeled cholesterol were assessed. Macrophage uptake of NPs did not induce cytotoxicity at concentrations utilized (25 μg/mL; however, macrophage exposure to 20 nm AgNPs reduced subsequent uptake of cholesterol. Further, we assessed the impact of a cholesterol-rich environment on macrophage function following NP exposure. In these sets of experiments, macrophages internalized NPs, exhibited no cytotoxicity, and altered cholesterol uptake. Alterations in the expression of scavenger receptor-B1 following NP exposure, which likely influences cholesterol uptake, were observed. Overall, NPs alter cholesterol uptake, which may have implications in the progression of vascular or immune mediated diseases. Therefore, for the safe development of NPs for biomedical applications, it is necessary to understand their impact on cellular function and biological interactions in underlying disease environments.

Key Roles of Size and Crystallinity of Nanosized Iron Hydr(oxides) Stabilized by Humic Substances in Iron Bioavailability to Plants.

Science.gov (United States)

Kulikova, Natalia A; Polyakov, Alexander Yu; Lebedev, Vasily A; Abroskin, Dmitry P; Volkov, Dmitry S; Pankratov, Denis A; Klein, Olga I; Senik, Svetlana V; Sorkina, Tatiana A; Garshev, Alexey V; Veligzhanin, Alexey A; Garcia Mina, Jose M; Perminova, Irina V

2017-12-27

Availability of Fe in soil to plants is closely related to the presence of humic substances (HS). Still, the systematic data on applicability of iron-based nanomaterials stabilized with HS as a source for plant nutrition are missing. The goal of our study was to establish a connection between properties of iron-based materials stabilized by HS and their bioavailability to plants. We have prepared two samples of leonardite HS-stabilized iron-based materials with substantially different properties using the reported protocols and studied their physical chemical state in relation to iron uptake and other biological effects. We used Mössbauer spectroscopy, XRD, SAXS, and TEM to conclude on iron speciation, size, and crystallinity. One material (Fe-HA) consisted of polynuclear iron(III) (hydr)oxide complexes, so-called ferric polymers, distributed in HS matrix. These complexes are composed of predominantly amorphous small-size components (Bioavailability studies were conducted on wheat plants under conditions of iron deficiency. The uptake studies have shown that small and amorphous ferric polymers were readily translocated into the leaves on the level of Fe-EDTA, whereas relatively large and crystalline feroxyhyte NPs were mostly sorbed on the roots. The obtained data are consistent with the size exclusion limits of cell wall pores (5-20 nm). Both samples demonstrated distinct beneficial effects with respect to photosynthetic activity and lipid biosynthesis. The obtained results might be of use for production of iron-based nanomaterials stabilized by HS with the tailored iron availability to plants. They can be applied as the only source for iron nutrition as well as in combination with the other elements, for example, for industrial production of "nanofortified" macrofertilizers (NPK).

Increased bone marrow uptake of gallium-67 in patients with fever of unknown origin

International Nuclear Information System (INIS)

Flores, L.G.; Jinnouchi, S.; Nagamachi, S.; Ohnishi, T.; Futami, S.; Watanabe, K.

1996-01-01

Purpose of the study: we studied the relationships of clinical diagnosis, the effect of blood chemistry and the clinical implication of increased gallium-67 in the bone marrow of patients presenting signs and symptoms of FUO. Materials and Methods: Based on intensity of gallium-67 uptake in bone marrow, patients were classified as follows: Type 1 when there is no evidence or very faint bone marrow uptake in vertebrae, Type 2 when mild to moderate, Type 3 when uptake is severe. The relationships of white blood cell count (WBC), hemoglobin concentration, hematocrit count, serum iron and unsaturated iron biding capacity (UIBC) with the occurrence of increased bone marrow uptake in the different groups were noted. Analysis of variance with Fishers Protected Least Significant Difference was used. A.p. value less than 0.05 was considered significant. Results: The results showed significant differences between Types 1 and 2 and between Type 1 and 3 for WBC counts, serum hemoglobin and serum hematocrit level. Serum iron concentration and UIBC however, did not show any significant differences. Conclusion: Significant changes in WBC count, Hb concentration and Hct count in FUO patients were accompanied by varying intensity of gallium-67 uptake in the bone marrow. (author)

Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

DEFF Research Database (Denmark)

Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

2012-01-01

is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead...... involved in iron transport. Iron and copper are mainly taken up at the BBB, but the BCB also plays a vital role in the homeostasis of the two metals, in terms of sequestering, uptake, and efflux of iron and copper from the brain. Inside the brain, iron and copper are taken up by neurons and glia cells...

Role of the Fur regulon in iron transport in Bacillus subtilis.

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Ollinger, Juliane; Song, Kyung-Bok; Antelmann, Haike; Hecker, Michael; Helmann, John D

2006-05-01

The Bacillus subtilis ferric uptake regulator (Fur) protein mediates the iron-dependent repression of at least 20 operons encoding approximately 40 genes. We investigated the physiological roles of Fur-regulated genes by the construction of null mutations in 14 transcription units known or predicted to function in siderophore biosynthesis or iron uptake. We demonstrate that ywbLMN, encoding an elemental iron uptake system orthologous to the copper oxidase-dependent Fe(III) uptake system of Saccharomyces cerevisiae, is essential for growth in low iron minimal medium lacking citric acid. 2,3-Dihydroxybenzoyl-glycine (Itoic acid), the siderophore precursor produced by laboratory strains of B. subtilis, is of secondary importance. In the presence of citrate, the YfmCDEF ABC transporter is required for optimal growth. B. subtilis is unable to grow in minimal medium containing the iron chelator EDDHA unless the ability to synthesize the intact bacillibactin siderophore is restored (by the introduction of a functional sfp gene) or exogenous siderophores are provided. Utilization of the catecholate siderophores bacillibactin and enterobactin requires the FeuABC importer and the YusV ATPase. Utilization of hydroxamate siderophores requires the FhuBGC ABC transporter together with the FhuD (ferrichrome) or YxeB (ferrioxamine) substrate-binding proteins. Growth with schizokinen or arthrobactin is at least partially dependent on the YfhA YfiYZ importer and the YusV ATPase. We have also investigated the effects of a fur mutation on the proteome and documented the derepression of 11 Fur-regulated proteins, including a newly identified thioredoxin reductase homolog, YcgT.

Ebselen inhibits iron-induced tau phosphorylation by attenuating DMT1 up-regulation and cellular iron uptake.

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Xie, Ling; Zheng, Wei; Xin, Na; Xie, Jing-Wei; Wang, Tao; Wang, Zhan-You

2012-08-01

Dysregulation of iron homeostasis is involved in the pathological process of Alzheimer's disease (AD). We have recently reported that divalent metal transporter 1 (DMT1) is upregulated in an AD transgenic mouse brain, and that silencing of DMT1, which reduces cellular iron influx, results in inhibition of amyloidogenesis in vitro, suggesting a potential target of DMT1 for AD therapy. In the present study, we tested the hypothesis that inhibition of DMT1 with ebselen, a DMT1 transport inhibitor, could affect tau phosphorylation. Human neuroblastoma SH-SY5Y cells were pre-treated with ebselen and then treated with ferrous sulfate (dissolved in ascorbic acid), and the effects of ebselen on tau phosphorylation and the relative signaling pathways were examined. Our results showed that ebselen decreased iron influx, reduced iron-induced ROS production, inhibited the activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3β, and ultimately attenuated the levels of tau phosphorylation at the sites of Thr205, Ser396 and Thr231. The present study indicates that the neuroprotective effect of ebselen on AD is not only related to its antioxidant activity as reported previously, but is also associated with a reduction in tau phosphorylation by inhibition of DMT1. Copyright © 2012 Elsevier Ltd. All rights reserved.

Accumulation of radioactive iron in marine organisms

International Nuclear Information System (INIS)

Tateda, Yuzuru

1985-01-01

The accumulation and excretion of radioactive iron in some marine organisms was investigated by radio-tracer experiments. The concentration factor, biological half-life, distribution in body, and combining form in some organs, are compared and discussed between mollusks and fishes. The results obtained are: 1) The concentration factor of seaweed was higher than those of worm and fish in uptake from seawater. Abalone showed a higher concentration factor than fish. 2) The first component of excretion curve was small in case of a longer period of uptake from seawater. 3) Abalone and octopus showed a higher radioactivity retention than flounder and black-fish. 4) The fish fed labelled seaweed showed a lower radioactivity retention than fish fed labelled worm. 5) The fish fed radioisotopes with prey showed a higher radioactivity retention than fish fed labelled prey. 6) Biological half-lives were longer in abalone and octopus than in fishes. The biological half-lives of radioactive iron in fishes varied according to the uptake modes. 7) The distribution ratio of radioactive iron in organisms were large in the liver and degestive tract. 8) The GFC profile of 59 Fe in some organs of organisms showed combining form of same molecular weight of proteinous matter. (author)

Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

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Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

2016-07-01

Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae

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Arkin Adam P

2009-03-01

Full Text Available Abstract Background Iron-deficiency anemia is the most prevalent form of anemia world-wide. The yeast Saccharomyces cerevisiae has been used as a model of cellular iron deficiency, in part because many of its cellular pathways are conserved. To better understand how cells respond to changes in iron availability, we profiled the yeast genome with a parallel analysis of homozygous deletion mutants to identify essential components and cellular processes required for optimal growth under iron-limited conditions. To complement this analysis, we compared those genes identified as important for fitness to those that were differentially-expressed in the same conditions. The resulting analysis provides a global perspective on the cellular processes involved in iron metabolism. Results Using functional profiling, we identified several genes known to be involved in high affinity iron uptake, in addition to novel genes that may play a role in iron metabolism. Our results provide support for the primary involvement in iron homeostasis of vacuolar and endosomal compartments, as well as vesicular transport to and from these compartments. We also observed an unexpected importance of the peroxisome for growth in iron-limited media. Although these components were essential for growth in low-iron conditions, most of them were not differentially-expressed. Genes with altered expression in iron deficiency were mainly associated with iron uptake and transport mechanisms, with little overlap with those that were functionally required. To better understand this relationship, we used expression-profiling of selected mutants that exhibited slow growth in iron-deficient conditions, and as a result, obtained additional insight into the roles of CTI6, DAP1, MRS4 and YHR045W in iron metabolism. Conclusion Comparison between functional and gene expression data in iron deficiency highlighted the complementary utility of these two approaches to identify important functional

Effect of sodium iron ethylenediaminetetraacetic acid on the absorption of various trace elements in anemic rats

International Nuclear Information System (INIS)

Igarashi, Kaori; Sasaki, Ayako; Yoda, Yoko; Inage, Hiroko; Nakanishi, Yukiko; Kimura, Shuichi; Yanagiya, Takahiro; Hirunuma, Rieko; Enomoto, Shuichi

2001-01-01

Iron deficiency in developing countries is attributed to the bioavailability of iron derived from staple food such as grains, vegetables and legumes. Sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), a strong metal chelator, is one of the food additives for iron fortification and it has been for improvement of iron deficiency in the world. However, the effect of NaFeEDTA on the absorption of trace elements other than Fe has been poorly understood. In the present study, to investigate the effect of NaFeEDTA on the absorption of trace elements, we determined the uptake rate of various metals using a multitracer technique. The uptake rates of Zn, Co, and Na in rats fed with NaFeEDTA diet were significantly lower than those in rats fed with ferrous sulfate (FS) diet, suggesting that iron fortification by NaFeEDTA lowers the bioavailability of various elements compared with FS. On the other hand, iron fortification using the FS diet in the presence of tannic acid decreased the bioavailability of Zn and Rb. However, no effect of tannic acid on the uptake rate of metal was observed in NaFeEDTA diet, suggesting that iron fortification using NaFeEDTA is less affected by tannic acid than that using the FS diet. These results indicate that iron fortification using NaFeEDTA is an effective method for improving iron deficiency. (author)

Superparamagnetic iron oxides for MRI

International Nuclear Information System (INIS)

Weissleder, R.; Reimer, P.

1993-01-01

Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous administration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrystalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. (orig.)

Superparamagnetic iron oxides for MRI

Energy Technology Data Exchange (ETDEWEB)

Weissleder, R [MGH-NMR Center, Dept. of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Reimer, P [MGH-NMR Center, Dept. of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); [Inst. fuer Klinische Radiologie, Zentrale Roentgendiagnostik, Westfaelische-Wilhelms-Univ., Muenster (Germany)

1993-06-01

Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous administration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrystalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. (orig.)

Structural and sequence analysis of imelysin-like proteins implicated in bacterial iron uptake.

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Qingping Xu

Full Text Available Imelysin-like proteins define a superfamily of bacterial proteins that are likely involved in iron uptake. Members of this superfamily were previously thought to be peptidases and were included in the MEROPS family M75. We determined the first crystal structures of two remotely related, imelysin-like proteins. The Psychrobacter arcticus structure was determined at 2.15 Å resolution and contains the canonical imelysin fold, while higher resolution structures from the gut bacteria Bacteroides ovatus, in two crystal forms (at 1.25 Å and 1.44 Å resolution, have a circularly permuted topology. Both structures are highly similar to each other despite low sequence similarity and circular permutation. The all-helical structure can be divided into two similar four-helix bundle domains. The overall structure and the GxHxxE motif region differ from known HxxE metallopeptidases, suggesting that imelysin-like proteins are not peptidases. A putative functional site is located at the domain interface. We have now organized the known homologous proteins into a superfamily, which can be separated into four families. These families share a similar functional site, but each has family-specific structural and sequence features. These results indicate that imelysin-like proteins have evolved from a common ancestor, and likely have a conserved function.

Divalent metal transporter 1 (DMT1) in the brain: implications for a role in iron transport at the blood-brain barrier, and neuronal and glial pathology.

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Skjørringe, Tina; Burkhart, Annette; Johnsen, Kasper Bendix; Moos, Torben

2015-01-01

Iron is required in a variety of essential processes in the body. In this review, we focus on iron transport in the brain and the role of the divalent metal transporter 1 (DMT1) vital for iron uptake in most cells. DMT1 locates to cellular membranes and endosomal membranes, where it is a key player in non-transferrin bound iron uptake and transferrin-bound iron uptake, respectively. Four isoforms of DMT1 exist, and their respective characteristics involve a complex cell-specific regulatory machinery all controlling iron transport across these membranes. This complexity reflects the fine balance required in iron homeostasis, as this metal is indispensable in many cell functions but highly toxic when appearing in excess. DMT1 expression in the brain is prominent in neurons. Of serious dispute is the expression of DMT1 in non-neuronal cells. Recent studies imply that DMT1 does exist in endosomes of brain capillary endothelial cells denoting the blood-brain barrier. This supports existing evidence that iron uptake at the BBB occurs by means of transferrin-receptor mediated endocytosis followed by detachment of iron from transferrin inside the acidic compartment of the endosome and DMT1-mediated pumping iron into the cytosol. The subsequent iron transport across the abluminal membrane into the brain likely occurs by ferroportin. The virtual absent expression of transferrin receptors and DMT1 in glial cells, i.e., astrocytes, microglia and oligodendrocytes, suggest that the steady state uptake of iron in glia is much lower than in neurons and/or other mechanisms for iron uptake in these cell types prevail.

Cloning and characterization of the iron uptake gene iutA from avian Escherichia coli

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Dorismey Vieira Tokano

2008-06-01

Full Text Available The aim of this work was to isolate, clone and characterize the iron uptake gene iutA from avian pathogenic E. coli (APEC. The iutA gene was isolated from the strain APEC 9, serotype O2:H9, which was cloned in the expression vector pET101/D-TOPO. The gene of 2.2 Kb was sequenced (AY602767, which showed high similarity to the iutA gene from three plasmids, two from APEC, pAPEC-02-ColV (AY545598.4 and pTJ100 (AY553855.1, and one from a human invasive E. coli strain, the pColV K30. The recombinant protein IutA was over expressed in E. coli BL21(DE-3 and was solubilized with urea and purified by Ni-NTA column. This method produced a relatively high yield of r-IutA of approximately 74kDa, which was used to produce the antibody anti-IutA. This anti-IutA reacted with the protein r-IutA and native IutA of APEC 9, as demonstrated by Western blot, showing that the r-IutA conserved epitopes and its antigenicity was preserved. The anti-IutA IgY was able to inhibit the IutA biological activity, inhibiting the sensitivity to cloacin DF13 of APEC9. However, it did not inhibit the growth of APEC9 in M9 and did not protect the chickens inoculated with the APEC, suggesting that the APEC possessed another iron acquisition mechanism distinct of aerobactin.A proteína de membrane externa IutA (iron uptake transport é o receptor para aerobactina férrica, um fator de virulência encontrado mais frequentemente entre as amostras de E. coli pathogênicas para aves (APEC do que entre os isolados fecais de aves saudáveis. O gene iutA da amostra APEC 9, sorotipo O2:H9, foi amplificado e clonado no vetor pET101/D-TOPO. O gene iutA 2.2 Kb foi sequenciado (AY602767 e mostrou alta similaridade para gene iutA de três plasmidios, dois da APEC, pAPEC-02-ColV (AY545598.4 e pTJ100 (AY553855.1, e um da amostra E. coli invasiva humana, pColV K30. A proteína IutA recombinante (r-IutA foi produzida em Escherichia coli BL21(DE-3, solubilizada com uréia e purificada em coluna de n

Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations.

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James R Connor

Full Text Available There is a significant clinical need for effective treatment of iron deficiency. A number of compounds that can be administered intravenously have been developed. This study examines how the compounds are handled by macrophages and their relative potential to provoke oxidative stress.Human kidney (HK-2 cells, rat peritoneal macrophages and renal cortical homogenates were exposed to pharmaceutical iron preparations. Analyses were performed for indices of oxidative stress and cell integrity. In addition, in macrophages, iron uptake and release and cytokine secretion was monitored.HK-2 cell viability was decreased by iron isomaltoside and ferumoxytol and all compounds induced lipid peroxidation. In the renal cortical homogenates, lipid peroxidation occurred at lowest concentrations with ferric carboxymaltose, iron dextran, iron sucrose and sodium ferric gluconate. In the macrophages, iron sucrose caused loss of cell viability. Iron uptake was highest for ferumoxytol and iron isomaltoside and lowest for iron sucrose and sodium ferric gluconate. Iron was released as secretion of ferritin or as ferrous iron via ferroportin. The latter was blocked by hepcidin. Exposure to ferric carboxymaltose and iron dextran resulted in release of tumor necrosis factor α.Exposure to iron compounds increased cell stress but was tissue and dose dependent. There was a clear difference in the handling of iron from the different compounds by macrophages that suggests in vivo responses may differ.

Diurnal variations in iron concentrations and expression of genes involved in iron absorption and metabolism in pigs.

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Zhang, Yiming; Wan, Dan; Zhou, Xihong; Long, Ciming; Wu, Xin; Li, Lan; He, Liuqin; Huang, Pan; Chen, Shuai; Tan, Bie; Yin, Yulong

2017-09-02

Diurnal variations in serum iron levels have been well documented in clinical studies, and serum iron is an important diagnostic index for iron-deficiency anemia. However, the underlying mechanism of dynamic iron regulation in response to the circadian rhythm is still unclear. In this study, we investigated daily variations in iron status in the plasma and liver of pigs. The transcripts encoding key factors involved in iron uptake and homeostasis were evaluated. The results showed that iron levels in the plasma and liver exhibited diurnal rhythms. Diurnal variations were also observed in transcript levels of divalent metal transporter 1 (DMT1), membrane-associated ferric reductase 1 (DCYTB), and transferrin receptor (TfR) in the duodenum and jejunum, as well as hepcidin (HAMP) and TfR in the liver. Moreover, the results showed a network in which diurnal variations in systemic iron levels were tightly regulated by hepcidin and Tf/TfR via DCYTB and DMT1. These findings provide new insights into circadian iron homeostasis regulation. The diurnal variations in serum iron levels may also have pathophysiological implications for clinical diagnostics related to iron deficiency anemia in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

Uranium uptake of Vetiveria zizanioides (L.) Nash

International Nuclear Information System (INIS)

Luu Viet Hung; Maslov, O.D.; Trinh Thi Thu My; Phung Khac Nam Ho; Dang Duc Nhan

2010-01-01

Uranium uptake of vetiver grass (Vetiveria zizanioides (L.) Nash) from Eutric Fluvisols (AK), Albic Acrisols (BG), Dystric Fluvisols (HP) and Ferralic Acrisols (TC) in northern Vietnam is assessed. The soils were mixed with aqueous solution of uranyl nitrate to make soils contaminated with uranium at 0, 50, 100, 250 mg/kg before planting the grass. The efficiency of uranium uptake by the grass was assessed based on the soil-to-plant transfer factor (TF U , kg·kg -1 ). It was found that the TF U values are dependent upon the soils properties. CEC facilitates the uptake and the increased soil pH could reduce the uptake and translocation of uranium in the plant. Organic matter content, as well as iron and potassium, inhibits the uranium uptake of the grass. It was revealed that the lower fertile soil, the higher uranium uptake. The translocation of uranium in root for all the soil types studied is almost higher than that in its shoot. It seems that vetiver grass could potentially be used for the purpose of phytoremediation of soils contaminated with uranium

Duodenal Cytochrome b (DCYTB in Iron Metabolism: An Update on Function and Regulation

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Darius J. R. Lane

2015-03-01

Full Text Available Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB; may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent “IRP1-HIF2α axis”; DCYTB and ascorbate in relation to iron metabolism.

[Iron and invasive fungal infection].

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Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

2013-01-01

Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Analysis method of intracellular iron accumulated in phytoplankton

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Jorge Falcão Paredes

1977-01-01

Full Text Available A colorimetric method for the assessment of iron accumulated in the cells of phytoplankton utilizing potassium ferrocyanide was developed. Two experiences with Phaeodactylum tricornutum and Chlorella sp. were carried out: the first one, on uptake of the iron relatively to the age of the culture: the second one, on the iron uptake by the cells, relatively to different concentrations of the chelator EDTA.Foi desenvolvido um método para análise do ferro acumulado em células de fitoplâncton, usando ferrocianeto de potássio como agente complexante. Com esse objetivo montaram-se duas experiências: uma em que se mostra o acúmulo de ferro em relação à idade das células e uma segunda experiência onde a assimilação é plotada em função da concentração de EDTA no meio de cultura.

Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition.

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Sheokand, Navdeep; Kumar, Santosh; Malhotra, Himanshu; Tillu, Vikas; Raje, Chaaya Iyengar; Raje, Manoj

2013-06-01

The long held view is that mammalian cells obtain transferrin (Tf) bound iron utilizing specialized membrane anchored receptors. Here we report that, during increased iron demand, cells secrete the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which enhances cellular uptake of Tf and iron. These observations could be mimicked by utilizing purified GAPDH injected into mice as well as when supplemented in culture medium of model cell lines and primary cell types that play a key role in iron metabolism. Transferrin and iron delivery was evaluated by biochemical, biophysical and imaging based assays. This mode of iron uptake is a saturable, energy dependent pathway, utilizing raft as well as non-raft domains of the cell membrane and also involves the membrane protein CD87 (uPAR). Tf internalized by this mode is also catabolized. Our research demonstrates that, even in cell types that express the known surface receptor based mechanism for transferrin uptake, more transferrin is delivered by this route which represents a hidden dimension of iron homeostasis. Iron is an essential trace metal for practically all living organisms however its acquisition presents major challenges. The current paradigm is that living organisms have developed well orchestrated and evolved mechanisms involving iron carrier molecules and their specific receptors to regulate its absorption, transport, storage and mobilization. Our research uncovers a hidden and primitive pathway of bulk iron trafficking involving a secreted receptor that is a multifunctional glycolytic enzyme that has implications in pathological conditions such as infectious diseases and cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

Roles for root iron plaque in sequestration and uptake of heavy metals and metalloids in aquatic and wetland plants.

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Tripathi, Rudra D; Tripathi, Preeti; Dwivedi, Sanjay; Kumar, Amit; Mishra, Aradhana; Chauhan, Puneet S; Norton, Gareth J; Nautiyal, Chandra S

2014-10-01

Toxic metal(loid) contamination of soil and sediment poses long term risk to soil and human health through plant-human or plant-animal-human food chain pathways. Iron plaque (IP) formation is frequent in aquatic and wetland plant species and is responsible for the sequestration of various metal(loids). The presence of IP may act as a buffer or barrier and may thus enhance or reduce the uptake of potentially phytotoxic metals and metalloids by plants. If IP acts as a barrier, then low IP producing macrophytes/aquatic plants may be better accumulators of toxic metals and may find use in constructed wetlands for remediation of pollutants, while high IP forming edible plant species could be safer for human consumption. Conversely, if IP acts as a buffer for mineral nutrients and toxic elements then those cultivars may be rich in nutrients, but may also cause toxicity. However, an ecotoxicological risk is also inevitable if IP rich macrophyte roots containing heavy metals are consumed by herbivores. In this review, we summarize the current understanding about the role of IP in metal and metalloid sequestration, uptake, and transport. Furthermore, we will address the role of root IP in Oryza sativa for arsenic (As) sequestration leading to lower grain As translocation, reducing the risk of human exposure.

SUPEROXIDE-DEPENDENT IRON UPTAKE: A NEW ROLE FOR ANION EXCHANGE PROTEIN 2

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Lung cells import iron across the plasma membrane as ferrous (Fe2+) ion by incompletely understood mechanisms. We tested the hypothesis that human bronchial epithelial (HBE) cells import non-transferrin-bound iron (NTBI) using superoxide-dependent ferri-reductase activity involvi...

Evaluating Iron Content and Tissue Microstructure with Off-Resonance Saturation MRI

Science.gov (United States)

Fahmy, Sherif R.

We present three magnetic resonance imaging (MRI) studies, each focused on applying off-resonance saturation (ORS) imaging to a different context or application. Particularly, we are interested in using ORS to evaluate the uptake of superparamagnetic MRI contrast agents in biological tissue, and to evaluate endogenous iron content. This relies on ORS being applied at low off-resonance frequency offsets where most of the negative contrast is due to signal loss from direct saturation of the water content of the sample. Additionally, we wish to combine this information with magnetization transfer contrast, which is obtained by applying ORS at offsets that are far from the resonance frequency, where magnetization transfer (MT) becomes the dominant effect rather than direct saturation (DS). In the first study, we observed the uptake of ultra-small superparamagnetic iron oxide (USPIO) nanoparticles in a simple model system by imaging the uptake in healthy murine liver in vivo, and by testing different metrics to quantify the uptake. Through this process, we discovered an approach that provides high sensitivity and specificity in low-signal scenarios. In the second study, we evaluated image contrast between brain regions in healthy human adults, and related these to the expected iron content in different regions based on age. Images were evaluated based on different MRI contrast mechanisms including quantitative transverse relaxation rates, as well as parameters obtained from ORS imaging. We also performed a field inhomogeneity adjustment on low-offset ORS data using the information obtained from the coarsely sampled ORS spectrum, and this was sufficient to correct for the inhomogeneities. In the third study, we used transverse relaxation, DS - which is strongly dependent on iron content, and MT contrast, in order to classify ex vivo brain samples having Alzheimer's disease pathology and normal controls, and were able to find strong classifiers. The three studies helped

Microbial iron management mechanisms in extremely acidic environments: comparative genomics evidence for diversity and versatility

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Nieto Pamela A

2008-11-01

Full Text Available Abstract Background Iron is an essential nutrient but can be toxic at high intracellular concentrations and organisms have evolved tightly regulated mechanisms for iron uptake and homeostasis. Information on iron management mechanisms is available for organisms living at circumneutral pH. However, very little is known about how acidophilic bacteria, especially those used for industrial copper bioleaching, cope with environmental iron loads that can be 1018 times the concentration found in pH neutral environments. This study was motivated by the need to fill this lacuna in knowledge. An understanding of how microorganisms thrive in acidic ecosystems with high iron loads requires a comprehensive investigation of the strategies to acquire iron and to coordinate this acquisition with utilization, storage and oxidation of iron through metal responsive regulation. In silico prediction of iron management genes and Fur regulation was carried out for three Acidithiobacilli: Acidithiobacillus ferrooxidans (iron and sulfur oxidizer A. thiooxidans and A. caldus (sulfur oxidizers that can live between pH 1 and pH 5 and for three strict iron oxidizers of the Leptospirillum genus that live at pH 1 or below. Results Acidithiobacilli have predicted FeoB-like Fe(II and Nramp-like Fe(II-Mn(II transporters. They also have 14 different TonB dependent ferri-siderophore transporters of diverse siderophore affinity, although they do not produce classical siderophores. Instead they have predicted novel mechanisms for dicitrate synthesis and possibly also for phosphate-chelation mediated iron uptake. It is hypothesized that the unexpectedly large number and diversity of Fe(III-uptake systems confers versatility to this group of acidophiles, especially in higher pH environments (pH 4–5 where soluble iron may not be abundant. In contrast, Leptospirilla have only a FtrI-Fet3P-like permease and three TonB dependent ferri-dicitrate siderophore systems. This paucity of iron

Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific Ocean

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Boiteau, Rene M.; Mende, Daniel R.; Hawco, Nicholas J.; McIlvin, Matthew R.; Fitzsimmons, Jessica N.; Saito, Mak A.; Sedwick, Peter N.; DeLong, Edward F.; Repeta, Daniel J.

2016-12-01

Nearly all iron dissolved in the ocean is complexed by strong organic ligands of unknown composition. The effect of ligand composition on microbial iron acquisition is poorly understood, but amendment experiments using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that siderophores, organic compounds synthesized by microbes to facilitate iron uptake, are a dynamic component of the marine ligand pool in the eastern tropical Pacific Ocean. Siderophore concentrations in iron-deficient waters averaged 9 pM, up to fivefold higher than in iron-rich coastal and nutrient-depleted oligotrophic waters, and were dominated by amphibactins, amphiphilic siderophores with cell membrane affinity. Phylogenetic analysis of amphibactin biosynthetic genes suggests that the ability to produce amphibactins has transferred horizontally across multiple Gammaproteobacteria, potentially driven by pressures to compete for iron. In coastal and oligotrophic regions of the eastern Pacific Ocean, amphibactins were replaced with lower concentrations (1-2 pM) of hydrophilic ferrioxamine siderophores. Our results suggest that organic ligand composition changes across the surface ocean in response to environmental pressures. Hydrophilic siderophores are predominantly found across regions of the ocean where iron is not expected to be the limiting nutrient for the microbial community at large. However, in regions with intense competition for iron, some microbes optimize iron acquisition by producing siderophores that minimize diffusive losses to the environment. These siderophores affect iron bioavailability and thus may be an important component of the marine iron cycle.

Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

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Singh, Ajay; Haldar, Swati; Horback, Katharine; Tom, Cynthia; Zhou, Lan; Meyerson, Howard; Singh, Neena

2017-01-01

Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP−/−). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP−/− mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP−/− mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP−/− mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP−/− BM-macrophages incorporate significantly less NTB-59Fe in the absence or presence of excess extracellular iron, indicating reduced uptake and/or storage of available iron in the absence of PrPC. When expressed in neuroblastoma cells, PrPC exhibits NAD(P)H-dependent cell-surface and intracellular FR activity that requires the copper-binding octa-peptide-repeat region and linkage to the plasma membrane for optimal function. Incorporation of NTB-59Fe by neuroblastoma cells correlates with FR activity of PrPC, implicating PrPC in cellular iron uptake and metabolism. These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. PMID:23478311

Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria.

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Troxell, Bryan; Hassan, Hosni M

2013-01-01

In the ancient anaerobic environment, ferrous iron (Fe(2+)) was one of the first metal cofactors. Oxygenation of the ancient world challenged bacteria to acquire the insoluble ferric iron (Fe(3+)) and later to defend against reactive oxygen species (ROS) generated by the Fenton chemistry. To acquire Fe(3+), bacteria produce low-molecular weight compounds, known as siderophores, which have extremely high affinity for Fe(3+). However, during infection the host restricts iron from pathogens by producing iron- and siderophore-chelating proteins, by exporting iron from intracellular pathogen-containing compartments, and by limiting absorption of dietary iron. Ferric Uptake Regulator (Fur) is a transcription factor which utilizes Fe(2+) as a corepressor and represses siderophore synthesis in pathogens. Fur, directly or indirectly, controls expression of enzymes that protect against ROS damage. Thus, the challenges of iron homeostasis and defense against ROS are addressed via Fur. Although the role of Fur as a repressor is well-documented, emerging evidence demonstrates that Fur can function as an activator. Fur activation can occur through three distinct mechanisms (1) indirectly via small RNAs, (2) binding at cis regulatory elements that enhance recruitment of the RNA polymerase holoenzyme (RNAP), and (3) functioning as an antirepressor by removing or blocking DNA binding of a repressor of transcription. In addition, Fur homologs control defense against peroxide stress (PerR) and control uptake of other metals such as zinc (Zur) and manganese (Mur) in pathogenic bacteria. Fur family members are important for virulence within bacterial pathogens since mutants of fur, perR, or zur exhibit reduced virulence within numerous animal and plant models of infection. This review focuses on the breadth of Fur regulation in pathogenic bacteria.

Sweden [Marine Radioecology. Current Research and Future Scope

International Nuclear Information System (INIS)

Agnedal, P.-O.

1967-01-01

The research which is going on now is concentrated on a study of uptake of cobalt, zinc and iron in the food chains in brackish water. We are following different lines in this work and they can be listed as follows: A. A study of accumulation and biological half-life of cobalt (later zinc and iron) in organisms in brackish water by means of radioactive isotopes. B. Analyses of stable elements (Co, Zn and Fe) in water, algae, evertebrates and fish from different localities in the Baltic and on the Swedish West Coast

Genome-Wide Search for Genes Required for Bifidobacterial Growth under Iron-Limitation

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Lanigan, Noreen; Bottacini, Francesca; Casey, Pat G.; O'Connell Motherway, Mary; van Sinderen, Douwe

2017-01-01

Bacteria evolved over millennia in the presence of the vital micronutrient iron. Iron is involved in numerous processes within the cell and is essential for nearly all living organisms. The importance of iron to the survival of bacteria is obvious from the large variety of mechanisms by which iron may be acquired from the environment. Random mutagenesis and global gene expression profiling led to the identification of a number of genes, which are essential for Bifidobacterium breve UCC2003 survival under iron-restrictive conditions. These genes encode, among others, Fe-S cluster-associated proteins, a possible ferric iron reductase, a number of cell wall-associated proteins, and various DNA replication and repair proteins. In addition, our study identified several presumed iron uptake systems which were shown to be essential for B. breve UCC2003 growth under conditions of either ferric and/or ferrous iron chelation. Of these, two gene clusters encoding putative iron-uptake systems, bfeUO and sifABCDE, were further characterised, indicating that sifABCDE is involved in ferrous iron transport, while the bfeUO-encoded transport system imports both ferrous and ferric iron. Transcription studies showed that bfeUO and sifABCDE constitute two separate transcriptional units that are induced upon dipyridyl-mediated iron limitation. In the anaerobic gastrointestinal environment ferrous iron is presumed to be of most relevance, though a mutation in the sifABCDE cluster does not affect B. breve UCC2003's ability to colonise the gut of a murine model. PMID:28620359

Genome-Wide Search for Genes Required for Bifidobacterial Growth under Iron-Limitation

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Noreen Lanigan

2017-05-01

Full Text Available Bacteria evolved over millennia in the presence of the vital micronutrient iron. Iron is involved in numerous processes within the cell and is essential for nearly all living organisms. The importance of iron to the survival of bacteria is obvious from the large variety of mechanisms by which iron may be acquired from the environment. Random mutagenesis and global gene expression profiling led to the identification of a number of genes, which are essential for Bifidobacterium breve UCC2003 survival under iron-restrictive conditions. These genes encode, among others, Fe-S cluster-associated proteins, a possible ferric iron reductase, a number of cell wall-associated proteins, and various DNA replication and repair proteins. In addition, our study identified several presumed iron uptake systems which were shown to be essential for B. breve UCC2003 growth under conditions of either ferric and/or ferrous iron chelation. Of these, two gene clusters encoding putative iron-uptake systems, bfeUO and sifABCDE, were further characterised, indicating that sifABCDE is involved in ferrous iron transport, while the bfeUO-encoded transport system imports both ferrous and ferric iron. Transcription studies showed that bfeUO and sifABCDE constitute two separate transcriptional units that are induced upon dipyridyl-mediated iron limitation. In the anaerobic gastrointestinal environment ferrous iron is presumed to be of most relevance, though a mutation in the sifABCDE cluster does not affect B. breve UCC2003's ability to colonise the gut of a murine model.

The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism.

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Lill, Roland; Hoffmann, Bastian; Molik, Sabine; Pierik, Antonio J; Rietzschel, Nicole; Stehling, Oliver; Uzarska, Marta A; Webert, Holger; Wilbrecht, Claudia; Mühlenhoff, Ulrich

2012-09-01

Mitochondria play a key role in iron metabolism in that they synthesize heme, assemble iron-sulfur (Fe/S) proteins, and participate in cellular iron regulation. Here, we review the latter two topics and their intimate connection. The mitochondrial Fe/S cluster (ISC) assembly machinery consists of 17 proteins that operate in three major steps of the maturation process. First, the cysteine desulfurase complex Nfs1-Isd11 as the sulfur donor cooperates with ferredoxin-ferredoxin reductase acting as an electron transfer chain, and frataxin to synthesize an [2Fe-2S] cluster on the scaffold protein Isu1. Second, the cluster is released from Isu1 and transferred toward apoproteins with the help of a dedicated Hsp70 chaperone system and the glutaredoxin Grx5. Finally, various specialized ISC components assist in the generation of [4Fe-4S] clusters and cluster insertion into specific target apoproteins. Functional defects of the core ISC assembly machinery are signaled to cytosolic or nuclear iron regulatory systems resulting in increased cellular iron acquisition and mitochondrial iron accumulation. In fungi, regulation is achieved by iron-responsive transcription factors controlling the expression of genes involved in iron uptake and intracellular distribution. They are assisted by cytosolic multidomain glutaredoxins which use a bound Fe/S cluster as iron sensor and additionally perform an essential role in intracellular iron delivery to target metalloproteins. In mammalian cells, the iron regulatory proteins IRP1, an Fe/S protein, and IRP2 act in a post-transcriptional fashion to adjust the cellular needs for iron. Thus, Fe/S protein biogenesis and cellular iron metabolism are tightly linked to coordinate iron supply and utilization. This article is part of a Special Issue entitled: Cell Biology of Metals. Copyright © 2012 Elsevier B.V. All rights reserved.

Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

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Quentin Philippot

Full Text Available Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor, storage (ferritin and export (ferroportin genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1 and the ratio between FEV1 and forced vital capacity (FEV1/FVC. The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively. In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative

Iron metabolism in mynah birds (Gracula religiosa) resembles human hereditary haemochromatosis

NARCIS (Netherlands)

Mete, A; Hendriks, HG; Klaren, PHM; Dorrestein, GM; van Dijk, JE; Marx, JJM

2003-01-01

Iron overload is a very frequent finding in several animal species and a genetic predisposition is suggested. In one of the most commonly reported species with susceptibility for iron overload ( mynah bird), it was recently shown that the cause of this pathophysiology is high uptake and retention of

Overexpression of Arabidopsis VIT1 increases accumulation of iron in cassava roots and stems

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Iron is extremely abundant in the soil, but its uptake in plants is limited due to low solubility in neutral or alkaline soils. Plants can rely on rhizosphere acidification to increase iron solubility. AtVIT1 was previously found to be involved in mediating vacuolar sequestration of iron, which indi...

Iron-dependent gene expression in Actinomyces oris

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Matthew P. Mulé

2015-12-01

Results: When A. oris was grown under iron-limiting conditions, the genes encoding iron/siderophore transporters fetA and sidD showed increased expression. One of these genes (sidD was mutated, and the sidD::Km strain exhibited a 50% reduction in growth in late log and stationary phase cells in media that contained iron. This growth defect was restored when the sidD gene was provided in a complemented strain. We were able to isolate the AmdR-encoding gene in seven clinical isolates of Actinomyces. When these protein sequences were aligned to the laboratory strain, there was a high degree of sequence similarity. Conclusions: The growth of the sidD::Km mutant in iron-replete medium mirrored the growth of the wild-type strain grown in iron-limiting medium, suggesting that the sidD::Km mutant was compromised in iron uptake. The known iron regulator AmdR is well conserved in clinical isolates of A. oris. This work provides additional insight into iron metabolism in this important oral microbe.

Uptake of magnetic nanoparticles into cells for cell tracking

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Becker, Christiane; Hodenius, Michael; Blendinger, Gitta; Sechi, Antonio; Hieronymus, Thomas; Mueller-Schulte, Detlef; Schmitz-Rode, Thomas; Zenke, Martin

2007-01-01

A challenge for future applications in nanotechnology is the functional integration of nano-sized materials into cellular structures. Here we investigated superparamagnetic Fe 3 O 4 iron oxide nanoparticles coated with a lipid bilayer for uptake into cells and for targeting subcellular compartments. It was found that magnetic nanoparticles (MNPs) are effectively taken up into cells and make cells acquire magnetic activity. Biotin-conjugated MNPs were further functionalized by binding of the fluorescent tag streptavidin-fluorescein isothiocyanate (FITC) and, following uptake into cells, shown to confer magnetic activity and fluorescence labeling. Such FITC-MNPs were localized in the lysosomal compartment of cells which suggests a receptor-mediated uptake mechanism

The Battle for Iron between Humans and Microbes.

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Carver, Peggy L

2018-01-01

Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment. To describe complex 'tug of war' for iron that has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. A review of current literature was performed, to assess current approaches and controversies in iron therapy and chelation in humans. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection. The administration of iron chelating agents and siderophore- conjugate drugs to infected hosts seems a biologically plausible approach as adjunctive therapy in the treatment of infections caused by pathogens dependent on host iron supply (e.g. tuberculosis, malaria, and many bacterial and fungal pathogens); however, thus far, studies in humans have proved unsuccessful. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

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Whiten, Shavonn R.; Eggleston, Heather; Adelman, Zach N.

2018-01-01

Heme and iron are essential molecules for many physiological processes and yet have the ability to cause oxidative damage such as lipid peroxidation, protein degradation, and ultimately cell death if not controlled. Blood-sucking arthropods have evolved diverse methods to protect themselves against iron/heme-related damage, as the act of bloodfeeding itself is high risk, high reward process. Protective mechanisms in medically important arthropods include the midgut peritrophic matrix in mosquitoes, heme aggregation into the crystalline structure hemozoin in kissing bugs and hemosomes in ticks. Once heme and iron pass these protective mechanisms they are presumed to enter the midgut epithelial cells via membrane-bound transporters, though relatively few iron or heme transporters have been identified in bloodsucking arthropods. Upon iron entry into midgut epithelial cells, ferritin serves as the universal storage protein and transport for dietary iron in many organisms including arthropods. In addition to its role as a nutrient, heme is also an important signaling molecule in the midgut epithelial cells for many physiological processes including vitellogenesis. This review article will summarize recent advancements in heme/iron uptake, detoxification and exportation in bloodfeeding arthropods. While initial strides have been made at ironing out the role of dietary iron and heme in arthropods, much still remains to be discovered as these molecules may serve as novel targets for the control of many arthropod pests. PMID:29387018

Quantification of nanowire uptake by live cells

KAUST Repository

Margineanu, Michael B.

2015-05-01

Nanostructures fabricated by different methods have become increasingly important for various applications at the cellular level. In order to understand how these nanostructures “behave” and for studying their internalization kinetics, several attempts have been made at tagging and investigating their interaction with living cells. In this study, magnetic iron nanowires with an iron oxide layer are coated with (3-Aminopropyl)triethoxysilane (APTES), and subsequently labeled with a fluorogenic pH-dependent dye pHrodo™ Red, covalently bound to the aminosilane surface. Time-lapse live imaging of human colon carcinoma HCT 116 cells interacting with the labeled iron nanowires is performed for 24 hours. As the pHrodo™ Red conjugated nanowires are non-fluorescent outside the cells but fluoresce brightly inside, internalized nanowires are distinguished from non-internalized ones and their behavior inside the cells can be tracked for the respective time length. A machine learning-based computational framework dedicated to automatic analysis of live cell imaging data, Cell Cognition, is adapted and used to classify cells with internalized and non-internalized nanowires and subsequently determine the uptake percentage by cells at different time points. An uptake of 85 % by HCT 116 cells is observed after 24 hours incubation at NW-to-cell ratios of 200. While the approach of using pHrodo™ Red for internalization studies is not novel in the literature, this study reports for the first time the utilization of a machine-learning based time-resolved automatic analysis pipeline for quantification of nanowire uptake by cells. This pipeline has also been used for comparison studies with nickel nanowires coated with APTES and labeled with pHrodo™ Red, and another cell line derived from the cervix carcinoma, HeLa. It has thus the potential to be used for studying the interaction of different types of nanostructures with potentially any live cell types.

Iron overload in myelodysplastic syndromes (MDS).

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Gattermann, Norbert

2018-01-01

Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

mRNA Levels of Placental Iron and Zinc Transporter Genes Are Upregulated in Gambian Women with Low Iron and Zinc Status.

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Jobarteh, Modou Lamin; McArdle, Harry J; Holtrop, Grietje; Sise, Ebrima A; Prentice, Andrew M; Moore, Sophie E

2017-07-01

Background: The role of the placenta in regulating micronutrient transport in response to maternal status is poorly understood. Objective: We investigated the effect of prenatal nutritional supplementation on the regulation of placental iron and zinc transport. Methods: In a randomized trial in rural Gambia [ENID (Early Nutrition and Immune Development)], pregnant women were allocated to 1 of 4 nutritional intervention arms: 1 ) iron and folic acid (FeFol) tablets (FeFol group); 2 ) multiple micronutrient (MMN) tablets (MMN group); 3 ) protein energy (PE) as a lipid-based nutrient supplement (LNS; PE group); and 4 ) PE and MMN (PE+MMN group) as LNS. All arms included iron (60 mg/d) and folic acid (400 μg/d). The MMN and PE+MMN arms included 30 mg supplemental Zn/d. In a subgroup of ∼300 mother-infant pairs, we measured maternal iron status, mRNA levels of genes encoding for placental iron and zinc transport proteins, and cord blood iron levels. Results: Maternal plasma iron concentration in late pregnancy was 45% and 78% lower in the PE and PE+MMN groups compared to the FeFol and MMN groups, respectively ( P Zinc supplementation in the MMN arm was associated with higher maternal plasma zinc concentrations (10% increase; P zinc-uptake proteins, in this case zrt, irt-like protein (ZIP) 4 and ZIP8, were 96-205% lower in the PE+MMN arm than in the intervention arms without added zinc ( P zinc, the placenta upregulates the gene expression of iron and zinc uptake proteins, presumably in order to meet fetal demands in the face of low maternal supply. The ENID trial was registered at www.controlled-trials.com as ISRCTN49285450.

Uptake, translocation and physiological effects of magnetic iron oxide (γ-Fe2O3) nanoparticles in corn (Zea mays L.).

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Li, Junli; Hu, Jing; Ma, Chuanxin; Wang, Yunqiang; Wu, Chan; Huang, Jin; Xing, Baoshan

2016-09-01

Iron oxide nanoparticles (γ-Fe2O3 NPs) have emerged as an innovative and promising method of iron application in agricultural systems. However, the possible toxicity of γ-Fe2O3 NPs and its uptake and translocation require further study prior to large-scale field application. In this study, we investigated uptake and distribution of γ-Fe2O3 NPs in corn (Zea mays L.) and its impacts on seed germination, antioxidant enzyme activity, malondialdehyde (MDA) content, and chlorophyll content were determined. 20 mg/L of γ-Fe2O3 NPs significantly promoted root elongation by 11.5%, and increased germination index and vigor index by 27.2% and 39.6%, respectively. However, 50 and 100 mg/L γ-Fe2O3 NPs remarkably decreased root length by 13.5% and 12.5%, respectively. Additionally, evidence for γ-Fe2O3 NPs induced oxidative stress was exclusively found in the root. Exposures of different concentrations of NPs induced notably high levels of MDA in corn roots, and the MDA levels of corn roots treated by γ-Fe2O3 NPs (20-100 mg/L) were 5-7-fold higher than that observed in the control plants. Meanwhile, the chlorophyll contents were decreased by 11.6%, 39.9% and 19.6%, respectively, upon NPs treatment relative to the control group. Images from fluorescence and transmission electron microscopy (TEM) indicated that γ-Fe2O3 NPs could enter plant roots and migrate apoplastically from the epidermis to the endodermis and accumulate the vacuole. Furthermore, we found that NPs mostly existed around the epidermis of root and no translocation of NPs from roots to shoots was observed. Our results will be highly meaningful on understanding the fate and physiological effects of γ-Fe2O3 NPs in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of iron bioavailability from different bread making processes using an in vitro intestinal cell model.

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Rodriguez-Ramiro, I; Brearley, C A; Bruggraber, S F A; Perfecto, A; Shewry, P; Fairweather-Tait, S

2017-08-01

Myo-inositol hexakisphosphate (IP6), is the main iron chelator in cereals and bread. The aim of this study was to investigate the effect of three commercial baking processes (sourdough, conventional yeast and Chorleywood Bread Making Process (CBP)) on the IP6 content of wholemeal bread, its impact on iron uptake in Caco-2 cells and the predicted bioavailability of iron from these breads with added iron, simulating a mixed-meal. The sourdough process fully degraded IP6 whilst the CBP and conventional processes reduced it by 75% compared with wholemeal flour. The iron released in solution after a simulated digestion was 8-fold higher in sourdough bread than with others but no difference in cellular iron uptake was observed. Additionally, when iron was added to the different breads digestions only sourdough bread elicited a significant ferritin response in Caco-2 cells (4.8-fold compared to the other breads) suggesting that sourdough bread could contribute towards improved iron nutrition. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Isolation and characterization of iron chelators from turmeric (Curcuma longa): selective metal binding by curcuminoids.

Science.gov (United States)

Messner, Donald J; Surrago, Christine; Fiordalisi, Celia; Chung, Wing Yin; Kowdley, Kris V

2017-10-01

Iron overload disorders may be treated by chelation therapy. This study describes a novel method for isolating iron chelators from complex mixtures including plant extracts. We demonstrate the one-step isolation of curcuminoids from turmeric, the medicinal food spice derived from Curcuma longa. The method uses iron-nitrilotriacetic acid (NTA)-agarose, to which curcumin binds rapidly, specifically, and reversibly. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin each bound iron-NTA-agarose with comparable affinities and a stoichiometry near 1. Analyses of binding efficiencies and purity demonstrated that curcuminoids comprise the primary iron binding compounds recovered from a crude turmeric extract. Competition of curcuminoid binding to the iron resin was used to characterize the metal binding site on curcumin and to detect iron binding by added chelators. Curcumin-Iron-NTA-agarose binding was inhibited by other metals with relative potency: (>90% inhibition) Cu 2+  ~ Al 3+  > Zn 2+  ≥ Ca 2+  ~ Mg 2+  ~ Mn 2+ (80% by addition of iron to the media; uptake was completely restored by desferoxamine. Ranking of metals by relative potencies for blocking curcumin uptake agreed with their relative potencies in blocking curcumin binding to iron-NTA-agarose. We conclude that curcumin can selectively bind toxic metals including iron in a physiological setting, and propose inhibition of curcumin binding to iron-NTA-agarose for iron chelator screening.

Iron colloids reduce the bioavailability of phosphorus to the green alga Raphidocelis subcapitata.

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Baken, Stijn; Nawara, Sophie; Van Moorleghem, Christoff; Smolders, Erik

2014-08-01

Phosphorus (P) is a limiting nutrient in many aquatic systems. The bioavailability of P in natural waters strongly depends on its speciation. In this study, structural properties of iron colloids were determined and related to their effect on P sorption and P bioavailability. The freshwater green alga Raphidocelis subcapitata was exposed to media spiked with radiolabelled (33)PO4, and the uptake of (33)P was monitored for 1 h. The media contained various concentrations of synthetic iron colloids with a size between 10 kDa and 0.45 μm. The iron colloids were stabilised by natural organic matter. EXAFS spectroscopy showed that these colloids predominantly consisted of ferrihydrite with small amounts of organically complexed Fe. In colloid-free treatments, the P uptake flux by the algae obeyed Michaelis-Menten kinetics. In the presence of iron colloids at 9 or 90 μM Fe, corresponding to molar P:Fe ratios between 0.02 and 0.17, the truly dissolved P (<10 kDa) was between 4 and 60% of the total dissolved P (<0.45 μm). These colloids reduced the P uptake flux by R. subcapitata compared to colloid-free treatments at the same total dissolved P concentration. However, the P uptake flux from colloid containing solutions equalled that from colloid-free ones when expressed as truly dissolved P. This demonstrates that colloidal P did not contribute to the P uptake flux. It is concluded that, on the short term, phosphate adsorbed to ferrihydrite colloids is not available to the green alga R. subcapitata. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging

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Claus-Christian Glüer

2010-12-01

Full Text Available Superparamagnetic iron-oxide particles (SPIO are used in different ways as contrast agents for magnetic resonance imaging (MRI: Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite, different coatings (none, dextran, carboxydextran, polystyrene and different hydrodynamic diameters (20–850 nm for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC, which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe3O4 particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.

Silicate reduces cadmium uptake into cells of wheat

International Nuclear Information System (INIS)

Greger, Maria; Kabir, Ahmad H.; Landberg, Tommy; Maity, Pooja J.; Lindberg, Sylvia

2016-01-01

Cadmium (Cd) is a health threat all over the world and high Cd content in wheat causes high Cd intake. Silicon (Si) decreases cadmium content in wheat grains and shoot. This work investigates whether and how silicate (Si) influences cadmium (Cd) uptake at the cellular level in wheat. Wheat seedlings were grown in the presence or absence of Si with or without Cd. Cadmium, Si, and iron (Fe) accumulation in roots and shoots was analysed. Leaf protoplasts from plants grown without Cd were investigated for Cd uptake in the presence or absence of Si using the fluorescent dye, Leadmium Green AM. Roots and shoots of plants subjected to all four treatments were investigated regarding the expression of genes involved in the Cd uptake across the plasma membrane (i.e. LCT1) and efflux of Cd into apoplasm or vacuole from the cytosol (i.e. HMA2). In addition, phytochelatin (PC) content and PC gene (PCS1) expression were analysed. Expression of iron and metal transporter genes (IRT1 and NRAMP1) were also analysed. Results indicated that Si reduced Cd accumulation in plants, especially in shoot. Si reduced Cd transport into the cytoplasm when Si was added both directly during the uptake measurements and to the growth medium. Silicate downregulated LCT1 and HMA2 and upregulated PCS1. In addition, Si enhanced PC formation when Cd was present. The IRT1 gene, which was downregulated by Cd was upregulated by Si in root and shoot facilitating Fe transport in wheat. NRAMP1 was similarly expressed, though the effect was limited to roots. This work is the first to show how Si influences Cd uptake on the cellular level. - Highlights: • Si decreases accumulation and translocation of Cd in plants at tissue level. • This work is the first to show how Si influences Cd uptake. • Si decreases Cd uptake into cell and downregulates heavy metal transporter LCT1. • Si downregulates HMA2 transporter, which regulates Cd transport from root to shoot. • Si increases phytochelatin formation

The iron-responsive microsomal proteome of Aspergillus fumigatus.

Science.gov (United States)

Moloney, Nicola M; Owens, Rebecca A; Meleady, Paula; Henry, Michael; Dolan, Stephen K; Mulvihill, Eoin; Clynes, Martin; Doyle, Sean

2016-03-16

Aspergillus fumigatus is an opportunistic fungal pathogen. Siderophore biosynthesis and iron acquisition are essential for virulence. Yet, limited data exist with respect to the adaptive nature of the fungal microsomal proteome under iron-limiting growth conditions, as encountered during host infection. Here, we demonstrate that under siderophore biosynthetic conditions--significantly elevated fusarinine C (FSC) and triacetylfusarinine C (TAFC) production (pproteome remodelling occurs. Specifically, a four-fold enrichment of transmembrane-containing proteins was observed with respect to whole cell lysates following ultracentrifugation-based microsomal extraction. Comparative label-free proteomic analysis of microsomal extracts, isolated following iron-replete and -deplete growth, identified 710 unique proteins. Scatterplot analysis (MaxQuant) demonstrated high correlation amongst biological replicates from each growth condition (Pearson correlation >0.96 within groups; biological replicates (n=4)). Quantitative and qualitative comparison revealed 231 proteins with a significant change in abundance between the iron-replete and iron-deplete conditions (pAspergillus fumigatus must acquire iron to facilitate growth and pathogenicity. Iron-chelating non-ribosomal peptides, termed siderophores, mediate iron uptake via membrane-localised transporter proteins. Here we demonstrate for the first time that growth of A. fumigatus under iron-deplete conditions, concomitant with siderophore biosynthesis, leads to an extensive remodelling of the microsomal proteome which includes significantly altered levels of 231 constituent proteins (96 increased and 135 decreased in abundance), many of which have not previously been localised to the microsome. We also demonstrate the first synthesis of a fluorescent version of fusarinine C, an extracellular A. fumigatus siderophore, and its uptake and localization under iron-restricted conditions. This infers the use of an A. fumigatus

Sodium nitroprusside may modulate Escherichia coli antioxidant enzyme expression by interacting with the ferric uptake regulator.

Science.gov (United States)

Bertrand, R; Danielson, D; Gong, V; Olynik, B; Eze, M O

2012-01-01

Efforts to explore possible relationships between nitric oxide (NO) and antioxidant enzymes in an Escherichia coli model have uncovered a possible interaction between sodium nitroprusside (SNP), a potent, NO-donating drug, and the ferric uptake regulator (Fur), an iron(II)--dependent regulator of antioxidant and iron acquisition proteins present in Gram-negative bacteria. The enzymatic profiles of superoxide dismutase and hydroperoxidase during logarithmic phase of growth were studied via non-denaturing polyacrylamide gel electrophoresis and activity staining specific to each enzyme. Though NO is known to induce transcription of the manganese-bearing isozyme of SOD (MnSOD), treatment with SNP paradoxically suppressed MnSOD expression and greatly enhanced the activity of the iron-containing equivalent (FeSOD). Fur, one of six global regulators of MnSOD transcription, is uniquely capable of suppressing MnSOD while enhancing FeSOD expression through distinct mechanisms. We thus hypothesize that Fur is complacent in causing this behaviour and that the iron(II) component of SNP is activating Fur. E. coli was also treated with the SNP structural analogues, potassium ferricyanide (PFi) and potassium ferrocyanide (PFo). Remarkably, the ferrous PFo was capable of mimicking the SNP-related pattern, whereas the ferric PFi was not. As Fur depends upon ferrous iron for activation, we submit this observation of redox-specificity as preliminary supporting evidence for the hypothesized Fur-SNP interaction. Iron is an essential metal that the human innate immune system sequesters to prevent its use by invading pathogens. As NO is known to inhibit iron-bound Fur, and as activated Fur regulates iron uptake through feedback inhibition, we speculate that the administration of this drug may disrupt this strategic management of iron in favour of residing Gram-negative species by providing a source of iron in an otherwise iron-scarce environment capable of encouraging its own uptake

Ceruloplasmin-ferroportin system of iron traffic in vertebrates

Institute of Scientific and Technical Information of China (English)

Giovanni; Musci; Fabio; Polticelli; Maria; Carmela; Bonaccorsi; di; Patti

2014-01-01

Safe trafficking of iron across the cell membrane is a delicate process that requires specific protein carriers. While many proteins involved in iron uptake by cells are known, only one cellular iron export protein has been identified in mammals: ferroportin(SLC40A1). Ceruloplasmin is a multicopper enzyme endowed with ferroxidase activity that is found as a soluble isoform in plasma or as a membrane-associated isoform in specific cell types. According to the currently accepted view, ferrous iron transported out of the cell by ferroportin would be safely oxidized by ceruloplasmin to facilitate loading on transferrin. Therefore, the ceruloplasminferroportin system represents the main pathway for cellular iron egress and it is responsible for physiological regulation of cellular iron levels. The most recent findings regarding the structural and functional features of ceruloplasmin and ferroportin and their relationship will be described in this review.

Uptake, translocation and transformation of antimony in rice (Oryza sativa L.) seedlings.

Science.gov (United States)

Cai, Fei; Ren, Jinghua; Tao, Shu; Wang, Xilong

2016-02-01

Antimony (Sb), as a toxic metalloid, has been gaining increasing research concerns due mainly to its severe pollution in many places. Rice has been identified to be the dominant intake route of Sb by residents close to the Sb mining areas. A hydroponic experiment was conducted to investigate the difference in uptake, translocation and transformation of Sb in rice seedlings of four cultivars exposed to 0.2 or 1.0 mg/L of Sb(V). The results showed that mass concentration of iron plaque (mg/kg FW) formed at the root surfaces of cultivar N was the highest among all tested cultivars at both low and high exposure levels of Sb(V). The accumulated Sb concentration in iron plaque significantly increased with an increase in mass concentration of iron plaque formed at the rice root. The total amount of iron plaque (mg/pot) at rice root generally increased with increasing exposed Sb(V) concentration, which was closely associated with the increasing lipid peroxidation in roots. Concentration percentage of Sb in rice root significantly reduced as the corresponding value in the iron plaque increased, suggesting that iron plaque formation strongly suppressed uptake of Sb by rice root. Sb concentration in rice tissues followed an order: root > stem, leaf. The japonica rice (cultivars N and Z) exhibited a stronger translocation tendency of Sb from root to stem than indica hybrid rice (cultivars F and G). Translocation of Sb from root of cultivar F to its stem and leaf was sharply enhanced with increasing Sb exposure concentration. Sb(V) could be reduced to Sb(III) in rice tissues, especially in stems (10-26% of the total Sb). For the sake of food safety, the difference in uptake, translocation and transformation of Sb in rice species planted in Sb-contaminated soils should be taken into consideration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of different iron compounds in chlorotic Italian lemon trees (Citrus lemon).

Science.gov (United States)

Ortiz, Patricio Rivera; Castro Meza, Blanca I; de la Garza Requena, Francisco R; Flores, Guillermo Mendoza; Etchevers Barra, Jorge D

2007-05-01

The severe deficiency of iron or ferric chlorosis is a serious problem of most citrus trees established in calcareous soils, as a result of the low availability of iron in these soils and the poor uptake and limited transport of this nutrient in trees. The objective of this study was to evaluate the response of chlorotic Italian lemon trees (Citrus lemon) to the application of iron compounds to roots and stems. On comparing the effects of aqueous solutions of ferric citrate, ferrous sulphate and FeEDDHA chelate, applied to 20% of the roots grown in soil and sand, of trees that were planted in pots containing calcareous soil, it was observed that the chelate fully corrected ferric chlorosis, while citrate and sulphate did not solve the problem. EDDHA induced the root uptake of iron as well as the movement of the nutrient up to the leaves. With the use of injections of ferric solutions into the secondary stem of adult trees, ferric citrate corrected chlorosis but ferrous sulphate did not. The citrate ion expanded the mobility of iron within the plant, from the injection points up to the leaves, whereas the sulphate ion did not sufficiently improve the movement of iron towards the leaf mesophyll.

Anemia of the Belgrade rat: evidence for defective membrane transport of iron

International Nuclear Information System (INIS)

Bowen, B.J.; Morgan, E.H.

1987-01-01

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59 Fe and 125 I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect

Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

Energy Technology Data Exchange (ETDEWEB)

Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

2015-02-01

Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

Increased cerebral iron uptake in Wilson's disease : A (52)Fe-citrate PET study

NARCIS (Netherlands)

Bruehlmeier, M; Leenders, KL; Vontobel, P; Calonder, C; Antonini, A; Weindl, A

Toxicity of abundant copper is the main cause of brain and liver tissue damage in patients with Wilson's disease (WD). However, there is also evidence of a disturbed iron metabolism in this genetically determined disorder. This PET study was undertaken to assess cerebral iron metabolism in WD

Cell tagging with clinically approved iron oxides: feasibility and effect of lipofection, particle size, and surface coating on labeling efficiency.

Science.gov (United States)

Matuszewski, Lars; Persigehl, Thorsten; Wall, Alexander; Schwindt, Wolfram; Tombach, Bernd; Fobker, Manfred; Poremba, Christopher; Ebert, Wolfgang; Heindel, Walter; Bremer, Christoph

2005-04-01

To evaluate the effect of lipofection, particle size, and surface coating on labeling efficiency of mammalian cells with superparamagnetic iron oxides (SPIOs). Institutional Review Board approval was not required. Different human cell lines (lung and breast cancer, fibrosarcoma, leukocytes) were tagged by using carboxydextran-coated SPIOs of various hydrodynamic diameters (17-65 nm) and a dextran-coated iron oxide (150 nm). Cells were incubated with increasing concentrations of iron (0.01-1.00 mg of iron [Fe] per milliliter), including or excluding a transfection medium (TM). Cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic emission spectroscopy. Cell visibility was assessed with gradient- and spin-echo magnetic resonance (MR) imaging. Effects of iron concentration in the medium and of lipofection on cellular SPIO uptake were analyzed with analysis of variance and two-tailed Student t test, respectively. Iron oxide uptake increased in a dose-dependent manner with higher iron concentrations in the medium. The TM significantly increased the iron load of cells (up to 2.6-fold, P .05). As few as 10 000 cells could be detected with clinically available MR techniques by using this approach. Lipofection-based cell tagging is a simple method for efficient cell labeling with clinically approved iron oxide-based contrast agents. Large particle size and carboxydextran coating are preferable for cell tagging with endocytosis- and lipofection-based methods. (c) RSNA, 2005.

Siderophore-dependent iron uptake systems as gates for antibiotic Trojan horse strategies against Pseudomonas aeruginosa.

Science.gov (United States)

Mislin, Gaëtan L A; Schalk, Isabelle J

2014-03-01

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen responsible for nosocomial infections. The prevalence of antibiotic-resistant P. aeruginosa strains is increasing, necessitating the urgent development of new strategies to improve the control of this pathogen. Its bacterial envelope constitutes of an outer and an inner membrane enclosing the periplasm. This structure plays a key role in the resistance of the pathogen, by decreasing the penetration and the biological impact of many antibiotics. However, this barrier may also be seen as the "Achilles heel" of the bacterium as some of its functions provide opportunities for breaching bacterial defenses. Siderophore-dependent iron uptake systems act as gates in the bacterial envelope and could be used in a "Trojan horse" strategy, in which the conjugation of an antibiotic to a siderophore could significantly increase the biological activity of the antibiotic, by enhancing its transport into the bacterium. In this review, we provide an overview of the various siderophore-antibiotic conjugates that have been developed for use against P. aeruginosa and show that an accurate knowledge of the structural and functional features of the proteins involved in this transmembrane transport is required for the design and synthesis of effective siderophore-antibiotic Trojan horse conjugates.

Analysis of ambient pH stress response mediated by iron and copper intake in Schizosaccharomyces pombe.

Science.gov (United States)

Higuchi, Yujiro; Mori, Hikari; Kubota, Takeo; Takegawa, Kaoru

2018-01-01

The molecular mechanism of tolerance to alkaline pH is well studied in model fungi Aspergillus nidulans and Saccharomyces cerevisiae. However, how fission yeast Schizosaccharomyces pombe survives under alkaline stress remains largely unknown, as the genes involved in the alkaline stress response pathways of A. nidulans and S. cerevisiae were not found in the genome of this organism. Since uptake of iron and copper into cells is important for alkaline tolerance in S. cerevisiae, here we examined whether iron and copper uptake processes were involved in conferring tolerance to alkaline stress in S. pombe. We first revealed that S. pombe wild-type strain could not grow at a pH higher than 6.7. We further found that the growths of mutants harboring disruption in the iron uptake-related gene frp1 + , fio1 + or fip1 + were severely inhibited under ambient pH stress condition. In contrast, derepression of these genes, by deletion of their repressor gene fep1 + , caused cells to acquire resistance to pH stress. Together, these results suggested that uptake of iron is essential for ambient pH tolerance in S. pombe. We also found that copper is required for the pH stress response because disruptants of ctr4 + , ctr5 + , ccc2 + and cuf1 + genes, all of which are needed for regulating intracellular Cu + , displayed ambient pH sensitivity. Furthermore, supplementing Fe 2+ and Cu 2+ ions to the culture media improved growth under ambient pH stress. Taken together, our results suggested that uptake of iron and copper is the crucial factor needed for the adaptation of S. pombe to ambient pH stress. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Identification of residues of FpvA involved in the different steps of Pvd-Fe uptake in Pseudomonas aeruginosa.

Science.gov (United States)

Nader, Mirella; Dobbelaere, Wim; Vincent, Michel; Journet, Laure; Adams, Hendrik; Cobessi, David; Gallay, Jacques; Schalk, Isabelle J

2007-10-23

FpvA is an outer membrane transporter involved in iron uptake by the siderophore pyoverdine (Pvd) in Pseudomonas aeruginosa. This transporter, like all other proteins of the same family, consists of a transmembrane 22 beta-stranded barrel occluded by a plug domain. The beta-strands of the barrel are connected by large extracellular loops and short periplasmic turns. Site-directed mutagenesis was carried out on FpvA to identify the extracellular loops or parts of these loops involved in the various stages of Pvd-Fe uptake. The G286C, W362C, and W434C mutations in loops L1, L3, and L4, respectively, disturbed the binding of the apo siderophore, as shown by time-resolved fluorescence spectroscopy. Iron uptake experiments followed by fluorescence resonance energy transfer (FRET) or using 55Fe indicated that residues W434 and G701 and, therefore, loops L4 and L9 must be involved in Pvd-Fe uptake by FpvA. The two corresponding mutants incorporated smaller than normal amounts of 55Fe into cells, and no Pvd recycling on FpvA was observed after iron release. Surprisingly, the S603C mutation in loop L7 increased the amount of Pvd-Fe transported. Our results suggest that W434 (L4), S603 (L7), and G701 (L9) are involved in the mechanism of Pvd-Fe uptake.

Phototrophs in high-iron-concentration microbial mats: physiological ecology of phototrophs in an iron-depositing hot spring

Science.gov (United States)

Pierson, B. K.; Parenteau, M. N.; Griffin, B. M.

1999-01-01

At Chocolate Pots Hot Springs in Yellowstone National Park the source waters have a pH near neutral, contain high concentrations of reduced iron, and lack sulfide. An iron formation that is associated with cyanobacterial mats is actively deposited. The uptake of [(14)C]bicarbonate was used to assess the impact of ferrous iron on photosynthesis in this environment. Photoautotrophy in some of the mats was stimulated by ferrous iron (1.0 mM). Microelectrodes were used to determine the impact of photosynthetic activity on the oxygen content and the pH in the mat and sediment microenvironments. Photosynthesis increased the oxygen concentration to 200% of air saturation levels in the top millimeter of the mats. The oxygen concentration decreased with depth and in the dark. Light-dependent increases in pH were observed. The penetration of light in the mats and in the sediments was determined. Visible radiation was rapidly attenuated in the top 2 mm of the iron-rich mats. Near-infrared radiation penetrated deeper. Iron was totally oxidized in the top few millimeters, but reduced iron was detected at greater depths. By increasing the pH and the oxygen concentration in the surface sediments, the cyanobacteria could potentially increase the rate of iron oxidation in situ. This high-iron-content hot spring provides a suitable model for studying the interactions of microbial photosynthesis and iron deposition and the role of photosynthesis in microbial iron cycling. This model may help clarify the potential role of photosynthesis in the deposition of Precambrian banded iron formations.

Phosphate Recovery From Sewage Sludge Containing Iron Phosphate

NARCIS (Netherlands)

Wilfert, P.K.

2018-01-01

The scope of this thesis was to lay the basis for a phosphate recovery technology that can be applied on sewage sludge containing iron phosphate. Such a technology should come with minimal changes to the existing sludge treatment configuration while keeping the use of chemicals or energy as small as

Interactions between iron(III)-hydroxide polymaltose complex and commonly used medications / laboratory studies in rats.

Science.gov (United States)

Funk, Felix; Canclini, Camillo; Geisser, Peter

2007-01-01

Simple iron salts, such as iron sulphate, often interact with food and other medications reducing bioavailability and tolerability. Iron(III)-hydroxide polymaltose complex (IPC, Maltofer) provides a soluble form of non-ionic iron, making it an ideal form of oral iron supplementation. The physicochemical properties of IPC predict a low potential for interactions. The effects of co-administration with aluminium hydroxide (CAS 21645-51-2), acetylsalicylic acid (CAS 50-78-2), bromazepam (CAS 1812-30-2), calcium acetate (CAS 62-54-4), calcium carbonate (CAS 471-34-1), auranofin (CAS 34031-32-8), magnesium-L-aspartate hydrochloride (CAS 28184-71-6), methyldopa sesquihydrate (CAS 41372-08-1), paracetamol (CAS 103-90-2), penicillamine (CAS 52-67-5), sulfasalazine (CAS 599-79-1), tetracycline hydrochloride (CAS 64-75-5), calcium phosphate (CAS 7757-93-9) in combination with vitamin D3 (CAS 67-97-0), and a multi-vitamin preparation were tested in rats fed an iron-deficient diet. Uptake of iron from radiolabelled IPC with and without concomitant medications was compared. None of the medicines tested had a significant effect on iron uptake. Iron-59 retrieval from blood and major storage organs was 64-76% for IPC alone compared with 59-85% following co-administration with other medications. It is concluded that, under normal clinical conditions, IPC does not interact with these medications.

The impact on atmospheric CO2 of iron fertilization induced changes in the ocean's biological pump

Science.gov (United States)

Jin, X.; Gruber, N.; Frenzel, H.; Doney, S. C.; McWilliams, J. C.

2008-03-01

Using numerical simulations, we quantify the impact of changes in the ocean's biological pump on the air-sea balance of CO2 by fertilizing a small surface patch in the high-nutrient, low-chlorophyll region of the eastern tropical Pacific with iron. Decade-long fertilization experiments are conducted in a basin-scale, eddy-permitting coupled physical/biogeochemical/ecological model. In contrast to previous studies, we find that most of the dissolved inorganic carbon (DIC) removed from the euphotic zone by the enhanced biological export is replaced by uptake of CO2 from the atmosphere. Atmospheric uptake efficiencies, the ratio of the perturbation in air-sea CO2 flux to the perturbation in export flux across 100 m, integrated over 10 years, are 0.75 to 0.93 in our patch size-scale experiments. The atmospheric uptake efficiency is insensitive to the duration of the experiment. The primary factor controlling the atmospheric uptake efficiency is the vertical distribution of the enhanced biological production and export. Iron fertilization at the surface tends to induce production anomalies primarily near the surface, leading to high efficiencies. In contrast, mechanisms that induce deep production anomalies (e.g. altered light availability) tend to have a low uptake efficiency, since most of the removed DIC is replaced by lateral and vertical transport and mixing. Despite high atmospheric uptake efficiencies, patch-scale iron fertilization of the ocean's biological pump tends to remove little CO2 from the atmosphere over the decadal timescale considered here.

Quality and Safety Assurance of Iron Casts and Manufacturing Processes

OpenAIRE

Kukla S.

2016-01-01

The scope of this work focuses on the aspects of quality and safety assurance of the iron cast manufacturing processes. Special attention was given to the processes of quality control and after-machining of iron casts manufactured on automatic foundry lines. Due to low level of automation and huge work intensity at this stage of the process, a model area was established which underwent reorganization in accordance with the assumptions of the World Class Manufacturing (WCM). An analysis of wor...

Pumping Iron and Silica Bodybuilding

Science.gov (United States)

Mcnair, H.; Brzezinski, M. A.; Krause, J. W.; Parker, C.; Brown, M.; Coale, T.; Bruland, K. W.

2016-02-01

The availability of dissolved iron influences the stoichiometry of nutrient uptake by diatoms. Under nutrient replete conditions diatoms consume silicic acid and nitrate in a 1:1 ratio, this ratio increases under iron stress. Using the tracers 32Si and PDMPO, the total community and group-specific silica production rates were measured along a gradient of dissolved iron in an upwelling plume off the California coast. At each station, a control (ambient silicic acid) and +20 µM silicic acid treatment were conducted with each tracer to determine whether silicic acid limitation controlled the rate of silica production. Dissolved iron was 1.3 nmol kg-1 nearshore and decreased to 0.15 nmol kg-1 offshore. Silicic acid decreased more rapidly than nitrate, it was nearly 9 µM higher in the nearshore and 7 µM lower than nitrate in the middle of the transect where the iron concentration had decreased. The rate of diatom silica production decreased in tandem with silicic acid concentration, and silica production limitation by low silicic acid was most pronounced when iron concentrations were >0.4 nmol kg-1. The composition of the diatom assemblage shifted from Chaetoceros spp. dominated nearshore to a more sparse pennate-dominated assemblage offshore. Changes in taxa-specific silica production rates will be reported based on examination of PDMPO labeled cells using confocal microscopy.

Comparative biogeochemical behaviors of iron-55 and stable iron in the marine environment

International Nuclear Information System (INIS)

Weimer, W.C.; Langford, J.C.; Jenkins, C.E.

1978-01-01

Studies of atmospheric aerosols have demonstrated that much of the 55 Fe associated with the aerosol input to the oceans is present as either an amorphous or hydrous iron oxide or as very small particulate species attached to the surfaces of the large aerosol particles. By comparison, nearly all of the stable iron is bound in the mineral phase of aerosol particles. This difference in the chemical and physical forms of the radioactive and stable iron isotopes results in the 55 Fe being more biologically available than is the stable iron. This difference in availability is responsible for the transfer of a much higher specific activity 55 Fe to certain ocean organisms and man relative to the specific activity of the total aerosol or of sea water. This differential biological uptake of the radioactive element and its stable element counterpart points out that natural levels of stable elements in the marine environment may not effectively dilute radioelements or other stable elements of anthropogenic sources. The effectiveness of dilution by natural sources depends on the chemical and physical forms of the materials in both the source terms and the receiving environments. The large difference in specific activities of 55 Fe in aerosols and sea water relative to ocean organisms reflects the independent behaviors of 55 Fe and stable iron

Regulation of iron metabolism during Neisseria meningitidis infection in mice

Energy Technology Data Exchange (ETDEWEB)

Letendre, E.D.

1984-01-01

Bacterial invasion of vertebrates triggers a marked reduction in the levels of iron associated with the plasma transferrin (Tf) pool. This hypoferremic response has been regarded as a host attempt to withhold essential iron from the invading pathogen. The exact nature of the mechanisms involved remains obscure. The kinetics of iron processing by the RE system were studied by labeling the RE compartments with /sup 59/Fe-labeled denatured red blood cells. Uptake and redistribution of the label indicated the RE-processed iron was not returned to the plasma Tf pool during the hypoferremia. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of home-derived iron into the intracellular ferritin pool and this produces the hypoferremia. The role of ceruloplasmin (ferroxidase I,EC.1.16.3.1) (Cp) in iron metabolism during meningococcal infection was investigated. Plasma Cp ferroxidase activity was found to increase greatly in mice during the convalescence phase.

Riboflavin Biosynthesis Is Associated with Assimilatory Ferric Reduction and Iron Acquisition by Campylobacter Jejuni.

NARCIS (Netherlands)

Gaskin, D.J.H.; Holmes, K.; Mulholland, F.; Wells, J.

2007-01-01

One of the pathways involved in the acquisition of the essential metal iron by bacteria involves the reduction of insoluble Fe3+ to soluble Fe2+, followed by transport of Fe2+ to the cytoplasm. Flavins have been implicated as electron donors in this poorly understood process. Ferrous iron uptake is

HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

Directory of Open Access Journals (Sweden)

Won Hee Jung

2010-11-01

Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs

Directory of Open Access Journals (Sweden)

Masanori Yoshinaga

2017-05-01

Full Text Available Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1, has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1−/− mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis.

Root excretions in tobacco plants and possible implications on the Iron nutrition of higher plants

Energy Technology Data Exchange (ETDEWEB)

Wallace, A

1969-01-01

Several pieces of evidence indicate that riboflavin produced in roots and perhaps other compounds produced either in roots or in microorganisms can facilitate either or both the absorption and translocation of iron in higher plants. Riboflavin production and increased iron transport are characteristic of iron-deficient plants, both are decreased by nitrogen deficiency, both evidently can be regulated by a microorganism. When large amounts of iron was transported in the xylem exudate of tobacco, riboflavin was also. An excess of the chelating agent, EDTA, without iron seems to increase the iron uptake from an iron chelate, EDDHA. All these effects are probably related and knowledge of them may help solve iron deficiency problems in horticultural crops.

Iron Acquisition in Bacillus cereus: The Roles of IlsA and Bacillibactin in Exogenous Ferritin Iron Mobilization

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Buisson, Christophe; Daou, Nadine; Kallassy, Mireille; Lereclus, Didier; Arosio, Paolo; Bou-Abdallah, Fadi; Nielsen Le Roux, Christina

2014-01-01

In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A) binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis. PMID:24550730

Iron acquisition in Bacillus cereus: the roles of IlsA and bacillibactin in exogenous ferritin iron mobilization.

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Diego Segond

2014-02-01

Full Text Available In host-pathogen interactions, the struggle for iron may have major consequences on the outcome of the disease. To overcome the low solubility and bio-availability of iron, bacteria have evolved multiple systems to acquire iron from various sources such as heme, hemoglobin and ferritin. The molecular basis of iron acquisition from heme and hemoglobin have been extensively studied; however, very little is known about iron acquisition from host ferritin, a 24-mer nanocage protein able to store thousands of iron atoms within its cavity. In the human opportunistic pathogen Bacillus cereus, a surface protein named IlsA (Iron-regulated leucine rich surface protein type A binds heme, hemoglobin and ferritin in vitro and is involved in virulence. Here, we demonstrate that IlsA acts as a ferritin receptor causing ferritin aggregation on the bacterial surface. Isothermal titration calorimetry data indicate that IlsA binds several types of ferritins through direct interaction with the shell subunits. UV-vis kinetic data show a significant enhancement of iron release from ferritin in the presence of IlsA indicating for the first time that a bacterial protein might alter the stability of the ferritin iron core. Disruption of the siderophore bacillibactin production drastically reduces the ability of B. cereus to utilize ferritin for growth and results in attenuated bacterial virulence in insects. We propose a new model of iron acquisition in B. cereus that involves the binding of IlsA to host ferritin followed by siderophore assisted iron uptake. Our results highlight a possible interplay between a surface protein and a siderophore and provide new insights into host adaptation of B. cereus and general bacterial pathogenesis.

The impact on atmospheric CO2 of iron fertilization induced changes in the ocean's biological pump

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J. C. McWilliams

2008-03-01

Full Text Available Using numerical simulations, we quantify the impact of changes in the ocean's biological pump on the air-sea balance of CO2 by fertilizing a small surface patch in the high-nutrient, low-chlorophyll region of the eastern tropical Pacific with iron. Decade-long fertilization experiments are conducted in a basin-scale, eddy-permitting coupled physical/biogeochemical/ecological model. In contrast to previous studies, we find that most of the dissolved inorganic carbon (DIC removed from the euphotic zone by the enhanced biological export is replaced by uptake of CO2 from the atmosphere. Atmospheric uptake efficiencies, the ratio of the perturbation in air-sea CO2 flux to the perturbation in export flux across 100 m, integrated over 10 years, are 0.75 to 0.93 in our patch size-scale experiments. The atmospheric uptake efficiency is insensitive to the duration of the experiment. The primary factor controlling the atmospheric uptake efficiency is the vertical distribution of the enhanced biological production and export. Iron fertilization at the surface tends to induce production anomalies primarily near the surface, leading to high efficiencies. In contrast, mechanisms that induce deep production anomalies (e.g. altered light availability tend to have a low uptake efficiency, since most of the removed DIC is replaced by lateral and vertical transport and mixing. Despite high atmospheric uptake efficiencies, patch-scale iron fertilization of the ocean's biological pump tends to remove little CO2 from the atmosphere over the decadal timescale considered here.

Siderophore production by pathogenic mucorales and uptake of deferoxamine B.

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Larcher, Gérald; Dias, Marylène; Razafimandimby, Bienvenue; Bomal, Danielle; Bouchara, Jean-Philippe

2013-12-01

Clinical reports have established that mucormycosis, mainly caused by Rhizopus spp., frequently occurs in patients treated with deferoxamine B (DFO, Desferal(®)) which is misappropriated by these fungi. Siderophore production by twenty mucoralean isolates was therefore investigated using a commercial iron-depleted culture medium. Siderophore production was detected for most of the isolates. Our experiments confirmed that feroxamine B (iron chelate of DFO) promoted in vitro growth of Rhizopus arrhizus. Electrophoretic analysis of somatic extracts revealed iron-regulated proteins of 60 and 32 kDa which were lacking in iron-depleted culture conditions. Using a fluorescent derivative of deferoxamine B, we showed by fluorescence microscopy the entry of the siderophore within the fungal cells, thus suggesting a shuttle mechanism encompassing the uptake of the entire siderophore-ion complex into the cell. This useful tool renders possible a better understanding of iron metabolism in Mucorales which could lead to the development of new diagnostic method or new antifungal therapy using siderophores as imaging contrast agents or active drug vectors.

Deciphering the iron isotope message of the human body

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Walczyk, Thomas; von Blanckenburg, Friedhelm

2005-04-01

Mass-dependent variations in isotopic composition are known since decades for the light elements such as hydrogen, carbon or oxygen. Multicollector-inductively coupled plasma mass spectrometry (MC-ICP-MS) and double-spike thermal ionization mass spectrometry (TIMS) permit us now to resolve small variations in isotopic composition even for the heavier elements such as iron. Recent studies on the iron isotopic composition of human blood and dietary iron sources have shown that lighter iron isotopes are enriched along the food chain and that each individual bears a certain iron isotopic signature in blood. To make use of this finding in biomedical research, underlying mechanisms of isotope fractionation by the human body need to be understood. In this paper available iron isotope data for biological samples are discussed within the context of isotope fractionation concepts and fundamental aspects of human iron metabolism. This includes evaluation of new data for body tissues which show that blood and muscle tissue have a similar iron isotopic composition while heavier iron isotopes are concentrated in the liver. This new observation is in agreement with our earlier hypothesis of a preferential absorption of lighter iron isotopes by the human body. Possible mechanisms for inducing an iron isotope effect at the cellular and molecular level during iron uptake are presented and the potential of iron isotope effects in human blood as a long-term measure of dietary iron absorption is discussed.

Use of /sup 59/Fe uptake in estimating the marrow dose in normal and splenectomized rats exposed to 1000 kVp x irradiation

Energy Technology Data Exchange (ETDEWEB)

Maillie, H D; Baxter, R C; Lisman, H [Rochester Univ., N.Y. (USA). School of Medicine and Dentistry

1977-11-01

The /sup 59/Fe uptake system was used to estimate the dose distribution throughout sham-operated and splenectomized rats exposed to whole-body 1000 kVp x irradiation. The marrow in the splenectomized animals was found to be slightly more radiosensitive. However, the difference between the two groups of rats was not significant. The dose distributions throughout the marrow of both groups were the same. It was concluded that splenectomy had no effect on the usefulness of this method. The method of measuring /sup 59/Fe uptake in this study used the uptake of radioiron at 6 hr post-injection and the deduction of the activity due to circulating iron. This resulted in a technique capable of measuring changes in iron uptake with midline-air-exposures of 25 R.

Recycled iron fuels new production in the eastern equatorial Pacific Ocean.

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Rafter, Patrick A; Sigman, Daniel M; Mackey, Katherine R M

2017-10-24

Nitrate persists in eastern equatorial Pacific surface waters because phytoplankton growth fueled by nitrate (new production) is limited by iron. Nitrate isotope measurements provide a new constraint on the controls of surface nitrate concentration in this region and allow us to quantify the degree and temporal variability of nitrate consumption. Here we show that nitrate consumption in these waters cannot be fueled solely by the external supply of iron to these waters, which occurs by upwelling and dust deposition. Rather, a substantial fraction of nitrate consumption must be supported by the recycling of iron within surface waters. Given plausible iron recycling rates, seasonal variability in nitrate concentration on and off the equator can be explained by upwelling rate, with slower upwelling allowing for more cycles of iron regeneration and uptake. The efficiency of iron recycling in the equatorial Pacific implies the evolution of ecosystem-level mechanisms for retaining iron in surface ocean settings where it limits productivity.

Nitric oxide and plant iron homeostasis.

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Buet, Agustina; Simontacchi, Marcela

2015-03-01

Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. © 2015 New York Academy of Sciences.

Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs.

Science.gov (United States)

Yoshinaga, Masanori; Nakatsuka, Yoshinari; Vandenbon, Alexis; Ori, Daisuke; Uehata, Takuya; Tsujimura, Tohru; Suzuki, Yutaka; Mino, Takashi; Takeuchi, Osamu

2017-05-23

Iron metabolism is regulated by transcriptional and post-transcriptional mechanisms. The mRNA of the iron-controlling gene, transferrin receptor 1 (TfR1), has long been believed to be negatively regulated by a yet-unidentified endonuclease. Here, we show that the endonuclease Regnase-1 is critical for the degradation of mRNAs involved in iron metabolism in vivo. First, we demonstrate that Regnase-1 promotes TfR1 mRNA decay. Next, we show that Regnase-1 -/- mice suffer from severe iron deficiency anemia, although hepcidin expression is downregulated. The iron deficiency anemia is induced by a defect in duodenal iron uptake. We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression. Finally, we show that Regnase-1 is a HIF2α-inducible gene and thus provides a positive feedback loop for HIF2α activation via PHD3. Collectively, these results demonstrate that Regnase-1-mediated regulation of iron-related transcripts is essential for the maintenance of iron homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Monoclonal antibodies against the iron regulated outer membrane Proteins of Acinetobacter baumannii are bactericidal

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Goel Vikas

2001-08-01

Full Text Available Abstract Background Iron is an important nutrient required by all forms of life.In the case of human hosts,the free iron availability is 10-18M,which is far less than what is needed for the survival of the invading bacterial pathogen.To survive in such conditions, bacteria express new proteins in their outer membrane and also secrete iron chelators called siderophores. Results/ Discussion Acinetobacter baumannii ATCC 19606, a nosocomial pathogen which grows under iron restricted conditions, expresses four new outer membrane proteins,with molecular weight ranging from 77 kDa to 88 kDa, that are called Iron Regulated Outer Membrane Proteins (IROMPs. We studied the functional and immunological properties of IROMPs expressed by A.baumanii ATCC 19606.The bands corresponding to IROMPs were eluted from SDS-PAGE and were used to immunize BALB/c mice for the production of monoclonal antibodies. Hybridomas secreting specific antibodies against these IROMPs were selected after screening by ELISA and their reactivity was confirmed by Western Blot. The antibodies then generated belonged to IgM isotype and showed bactericidical and opsonising activities against A.baumanii in vitro.These antibodies also blocked siderophore mediated iron uptake via IROMPs in bacteria. Conclusion This proves that iron uptake via IROMPs,which is mediated through siderophores,may have an important role in the survival of A.baumanii inside the host,and helps establishing the infection.

Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

International Nuclear Information System (INIS)

Penno, E.; Johnsson, C.; Johansson, L.; Ahlstroem, H.

2006-01-01

Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection

Heme and non-heme iron transporters in non-polarized and polarized cells

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Yasui Yumiko

2010-06-01

Full Text Available Abstract Background Heme and non-heme iron from diet, and recycled iron from hemoglobin are important products of the synthesis of iron-containing molecules. In excess, iron is potentially toxic because it can produce reactive oxygen species through the Fenton reaction. Humans can absorb, transport, store, and recycle iron without an excretory system to remove excess iron. Two candidate heme transporters and two iron transporters have been reported thus far. Heme incorporated into cells is degraded by heme oxygenases (HOs, and the iron product is reutilized by the body. To specify the processes of heme uptake and degradation, and the reutilization of iron, we determined the subcellular localizations of these transporters and HOs. Results In this study, we analyzed the subcellular localizations of 2 isoenzymes of HOs, 4 isoforms of divalent metal transporter 1 (DMT1, and 2 candidate heme transporters--heme carrier protein 1 (HCP1 and heme responsive gene-1 (HRG-1--in non-polarized and polarized cells. In non-polarized cells, HCP1, HRG-1, and DMT1A-I are located in the plasma membrane. In polarized cells, they show distinct localizations: HCP1 and DMT1A-I are located in the apical membrane, whereas HRG-1 is located in the basolateral membrane and lysosome. 16Leu at DMT1A-I N-terminal cytosolic domain was found to be crucial for plasma membrane localization. HOs are located in smooth endoplasmic reticulum and colocalize with NADPH-cytochrome P450 reductase. Conclusions HCP1 and DMT1A-I are localized to the apical membrane, and HRG-1 to the basolateral membrane and lysosome. These findings suggest that HCP1 and DMT1A-I have functions in the uptake of dietary heme and non-heme iron. HRG-1 can transport endocytosed heme from the lysosome into the cytosol. These localization studies support a model in which cytosolic heme can be degraded by HOs, and the resulting iron is exported into tissue fluids via the iron transporter ferroportin 1, which is

Towards a Mechanistic Understanding of Anaerobic Nitrate Dependent Iron Oxidation: Balancing Electron Uptake and Detoxification

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Hans Karl Carlson

2012-02-01

Full Text Available The anaerobic oxidation of Fe(II by subsurface microorganisms is an important part of biogeochemical cycling in the environment, but the biochemical mechanisms used to couple iron oxidation to nitrate respiration are not well understood. Based on our own work and the evidence available in the literature, we propose a mechanistic model for anaerobic nitrate dependent iron oxidation. We suggest that anaerobic iron oxidizing microorganisms likely exist along a continuum including: 1 bacteria that inadvertently oxidize Fe(II by abiotic or biotic reactions with enzymes or chemical intermediates in their metabolic pathways (e.g. denitrification and suffer from toxicity or energetic penalty, 2 Fe(II tolerant bacteria that gain little or no growth benefit from iron oxidation but can manage the toxic reactions, and 3 bacteria that efficiently accept electrons from Fe(II to gain a growth advantage while preventing or mitigating the toxic reactions. Predictions of the proposed model are highlighted and experimental approaches are discussed.

Influence of chelating ligands on arsenic uptake by hydroponically grown rice seedlings (Oryza sativa L.): a preliminary study

Energy Technology Data Exchange (ETDEWEB)

Rahman, Mohammad A.; Hasegawa, Hiroshi; Ueda, Kazumasa; Maki, Teruya [Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa (Japan); Rahman, M.M. [Department of Botany, Faculty of Biological Sciences, Jahangirnagar University, Savar, Dhaka (Bangladesh)

2008-06-15

Ferric (oxyhydro-)oxides (FeO{sub x}) precipitate in the rhizosphere at neutral or alkaline pH and are adsorbed on the plant root surfaces. Consequently, the higher binding affinity of arsenate to FeO{sub x} and the low iron phytoavailability of the precipitated FeO{sub x} make the phytoremediation of arsenic difficult. In the present study, the influence of chelating ligands on arsenic and iron uptake by hydroponically grown rice seedlings (Oryza sativa L.) was investigated. When chelating ligands were not treated to the growth medium, about 63 and 71% of the total arsenic and iron were distributed in the root extract (outer root surfaces) of rice, respectively. On the other hand, ethylenediaminetetraacetic acid (EDTA), ethylenediaminedisuccinic acid (EDDS) and hydroxyiminodisuccinic acid (HIDS) desorbed a significant amount of arsenic from FeO{sub x} of the outer root surfaces. Therefore, the uptake of arsenic and iron into the roots and their subsequent translocation to the shoots of the rice seedlings increased significantly. The order of increasing arsenic uptake by chelating ligands was HIDS > EDTA > EDDS. Methylglycinediacetic acid (MGDA) and iminodisuccinic acid (IDS) might not be effective in arsenic solubilization from FeO{sub x}. The results suggest that EDDS and HIDS would be a good and environmentally safe choice to accelerate arsenic phytoavailability in the phytoremediation process because of their biodegradability and would be a competent alternative to the widely used non-biodegradable and environmentally persistent EDTA. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

Microbial Community Composition Impacts Pathogen Iron Availability during Polymicrobial Infection.

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Apollo Stacy

2016-12-01

Full Text Available Iron is an essential nutrient for bacterial pathogenesis, but in the host, iron is tightly sequestered, limiting its availability for bacterial growth. Although this is an important arm of host immunity, most studies examine how bacteria respond to iron restriction in laboratory rather than host settings, where the microbiome can potentially alter pathogen strategies for acquiring iron. One of the most important transcriptional regulators controlling bacterial iron homeostasis is Fur. Here we used a combination of RNA-seq and chromatin immunoprecipitation (ChIP-seq to characterize the iron-restricted and Fur regulons of the biofilm-forming opportunistic pathogen Aggregatibacter actinomycetemcomitans. We discovered that iron restriction and Fur regulate 4% and 3.5% of the genome, respectively. While most genes in these regulons were related to iron uptake and metabolism, we found that Fur also directly regulates the biofilm-dispersing enzyme Dispersin B, allowing A. actinomycetemcomitans to escape from iron-scarce environments. We then leveraged these datasets to assess the availability of iron to A. actinomycetemcomitans in its primary infection sites, abscesses and the oral cavity. We found that A. actinomycetemcomitans is not restricted for iron in a murine abscess mono-infection, but becomes restricted for iron upon co-infection with the oral commensal Streptococcus gordonii. Furthermore, in the transition from health to disease in human gum infection, A. actinomycetemcomitans also becomes restricted for iron. These results suggest that host iron availability is heterogeneous and dependent on the infecting bacterial community.

A relay network of extracellular heme-binding proteins drives C. albicans iron acquisition from hemoglobin.

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Kuznets, Galit; Vigonsky, Elena; Weissman, Ziva; Lalli, Daniela; Gildor, Tsvia; Kauffman, Sarah J; Turano, Paola; Becker, Jeffrey; Lewinson, Oded; Kornitzer, Daniel

2014-10-01

Iron scavenging constitutes a crucial challenge for survival of pathogenic microorganisms in the iron-poor host environment. Candida albicans, like many microbial pathogens, is able to utilize iron from hemoglobin, the largest iron pool in the host's body. Rbt5 is an extracellular glycosylphosphatidylinositol (GPI)-anchored heme-binding protein of the CFEM family that facilitates heme-iron uptake by an unknown mechanism. Here, we characterize an additional C. albicans CFEM protein gene, PGA7, deletion of which elicits a more severe heme-iron utilization phenotype than deletion of RBT5. The virulence of the pga7-/- mutant is reduced in a mouse model of systemic infection, consistent with a requirement for heme-iron utilization for C. albicans pathogenicity. The Pga7 and Rbt5 proteins exhibit distinct cell wall attachment, and discrete localization within the cell envelope, with Rbt5 being more exposed than Pga7. Both proteins are shown here to efficiently extract heme from hemoglobin. Surprisingly, while Pga7 has a higher affinity for heme in vitro, we find that heme transfer can occur bi-directionally between Pga7 and Rbt5, supporting a model in which they cooperate in a heme-acquisition relay. Together, our data delineate the roles of Pga7 and Rbt5 in a cell surface protein network that transfers heme from extracellular hemoglobin to the endocytic pathway, and provide a paradigm for how receptors embedded in the cell wall matrix can mediate nutrient uptake across the fungal cell envelope.

Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake

DEFF Research Database (Denmark)

Inturi, Swetha; Wang, Guankui; Chen, Fangfang

2015-01-01

demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface...... by epichlorohydrin decreased C3 opsonization in mouse serum, and consequently reduced the uptake by mouse leukocytes by more than 70% in vivo. Remarkably, the cross-linked particles did not show a decrease in C3 opsonization in human serum, but showed a significant decrease (over 60%) of the uptake by human...... leukocytes. The residual uptake of cross-linked nanoparticles was completely blocked by EDTA. These findings demonstrate species differences in complement-mediated nanoparticle recognition and uptake by leukocytes, and further show that human hemocompatibility could be improved by inhibitors of complement...

Influence of sodium humate on the growth of Scenedesmus quadricauda (Turp. Brèb. and Gonium pectorale in the case of different calciumand iron doses

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Krystyna Juraja

2015-01-01

Full Text Available The influence of sodium humate on calcium and iron uptake by two species of algae was studied. It was found that sodium humate influence differentially the growth of these algae in various culture conditions by regulating the iron uptake. The action of sodium humate is especially favourable in non optimal pH of the medium and its effectiveness increases with time.

Prion protein modulates glucose homeostasis by altering intracellular iron.

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Ashok, Ajay; Singh, Neena

2018-04-26

The prion protein (PrP C ), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP -/- ) were significantly lower than wild type (PrP +/+ ) controls. Silencing of PrP C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP C -dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP +/+ but not PrP -/- mice, indicating PrP C -mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP +/+ relative to PrP -/- mice, suggesting that PrP C -mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer's disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

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Mey, Alexandra R.; Wyckoff, Elizabeth E.

2015-01-01

SUMMARY Iron is an essential element for Vibrio spp., but the acquisition of iron is complicated by its tendency to form insoluble ferric complexes in nature and its association with high-affinity iron-binding proteins in the host. Vibrios occupy a variety of different niches, and each of these niches presents particular challenges for acquiring sufficient iron. Vibrio species have evolved a wide array of iron transport systems that allow the bacteria to compete for this essential element in each of its habitats. These systems include the secretion and uptake of high-affinity iron-binding compounds (siderophores) as well as transport systems for iron bound to host complexes. Transporters for ferric and ferrous iron not complexed to siderophores are also common to Vibrio species. Some of the genes encoding these systems show evidence of horizontal transmission, and the ability to acquire and incorporate additional iron transport systems may have allowed Vibrio species to more rapidly adapt to new environmental niches. While too little iron prevents growth of the bacteria, too much can be lethal. The appropriate balance is maintained in vibrios through complex regulatory networks involving transcriptional repressors and activators and small RNAs (sRNAs) that act posttranscriptionally. Examination of the number and variety of iron transport systems found in Vibrio spp. offers insights into how this group of bacteria has adapted to such a wide range of habitats. PMID:26658001

In Vitro Iron Bioavailability of Brazilian Food-Based by-Products.

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Chiocchetti, Gabriela M; De Nadai Fernandes, Elisabete A; Wawer, Anna A; Fairweather-Tait, Susan; Christides, Tatiana

2018-05-16

Background : Iron deficiency is a public health problem in many low- and middle-income countries. Introduction of agro-industrial food by-products, as additional source of nutrients, could help alleviate this micronutrient deficiency, provide alternative sources of nutrients and calories in developed countries, and be a partial solution for disposal of agro-industry by-products. Methods : The aim of this study was to determine iron bioavailability of 5 by-products from Brazilian agro-industry (peels from cucumber, pumpkin, and jackfruit, cupuaçu seed peel, and rice bran), using the in vitro digestion/ Caco-2 cell model; with Caco-2 cell ferritin formation as a surrogate marker of iron bioavailability. Total and dialyzable Fe, macronutrients, the concentrations of iron-uptake inhibitors (phytic acid, tannins, fiber) and their correlation with iron bioavailability were also evaluated. Results : The iron content of all by-products was high, but the concentration of iron and predicted bioavailability were not related. Rice bran and cupuaçu seed peel had the highest amount of phytic acid and tannins, and lowest iron bioavailability. Cucumber peels alone, and with added extrinsic Fe, and pumpkin peels with extrinsic added iron, had the highest iron bioavailability. Conclusion : The results suggest that cucumber and pumpkin peel could be valuable alternative sources of bioavailable Fe to reduce iron deficiency in at-risk populations.

Iron control on global productivity: an efficient inverse model of the ocean's coupled phosphate and iron cycles.

Science.gov (United States)

Pasquier, B.; Holzer, M.; Frants, M.

2016-02-01

We construct a data-constrained mechanistic inverse model of the ocean's coupled phosphorus and iron cycles. The nutrient cycling is embedded in a data-assimilated steady global circulation. Biological nutrient uptake is parameterized in terms of nutrient, light, and temperature limitations on growth for two classes of phytoplankton that are not transported explicitly. A matrix formulation of the discretized nutrient tracer equations allows for efficient numerical solutions, which facilitates the objective optimization of the key biogeochemical parameters. The optimization minimizes the misfit between the modelled and observed nutrient fields of the current climate. We systematically assess the nonlinear response of the biological pump to changes in the aeolian iron supply for a variety of scenarios. Specifically, Green-function techniques are employed to quantify in detail the pathways and timescales with which those perturbations are propagated throughout the world oceans, determining the global teleconnections that mediate the response of the global ocean ecosystem. We confirm previous findings from idealized studies that increased iron fertilization decreases biological production in the subtropical gyres and we quantify the counterintuitive and asymmetric response of global productivity to increases and decreases in the aeolian iron supply.

Decreased bone uptake of technetium-99m polyphosphate in thalassemia major

International Nuclear Information System (INIS)

Valdez, V.A.; Jacobstein, J.G.

1980-01-01

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renal enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings

Physico-chemical properties of the new generation IV iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose.

Science.gov (United States)

Neiser, Susann; Rentsch, Daniel; Dippon, Urs; Kappler, Andreas; Weidler, Peter G; Göttlicher, Jörg; Steininger, Ralph; Wilhelm, Maria; Braitsch, Michaela; Funk, Felix; Philipp, Erik; Burckhardt, Susanna

2015-08-01

The advantage of the new generation IV iron preparations ferric carboxymaltose (FCM), ferumoxytol (FMX), and iron isomaltoside 1000 (IIM) is that they can be administered in relatively high doses in a short period of time. We investigated the physico-chemical properties of these preparations and compared them with those of the older preparations iron sucrose (IS), sodium ferric gluconate (SFG), and low molecular weight iron dextran (LMWID). Mössbauer spectroscopy, X-ray diffraction, and Fe K-edge X-ray absorption near edge structure spectroscopy indicated akaganeite structures (β-FeOOH) for the cores of FCM, IIM and IS, and a maghemite (γ-Fe2O3) structure for that of FMX. Nuclear magnetic resonance studies confirmed the structure of the carbohydrate of FMX as a reduced, carboxymethylated, low molecular weight dextran, and that of IIM as a reduced Dextran 1000. Polarography yielded significantly different fingerprints of the investigated compounds. Reductive degradation kinetics of FMX was faster than that of FCM and IIM, which is in contrast to the high stability of FMX towards acid degradation. The labile iron content, i.e. the amount of iron that is only weakly bound in the polynuclear iron core, was assessed by a qualitative test that confirmed decreasing labile iron contents in the order SFG ≈ IS > LMWID ≥ FMX ≈ IIM ≈ FCM. The presented data are a step forward in the characterization of these non-biological complex drugs, which is a prerequisite to understand their cellular uptake mechanisms and the relationship between the structure and physiological safety as well as efficacy of these complexes.

Labeling Efficacy of Superparamagnetic Iron Oxide Nanoparticles to Human Neural Stem Cells: Comparison of Ferumoxides, Monocrystalline Iron Oxide, Cross-linked Iron Oxide (CLIO)-NH2 and tat-CLIO

International Nuclear Information System (INIS)

Song, Mi Yeoun; Moon, Woo Kyung; Kim, Yun Hee; Song, In Chan; Yoon, Byung Woo; Lim, Dong Yeol

2007-01-01

We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH 2 and tat-CLIO. The hNSCs (5x10 5 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 μg/ml of ferumoxides, MION or CLIO-NH 2 , and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15± 0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH 2 , respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH 2 into the hNSCs was comparable to that of tat-CLIO. For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH 2 and the transfection agent PLL

Labeling Efficacy of Superparamagnetic Iron Oxide Nanoparticles to Human Neural Stem Cells: Comparison of Ferumoxides, Monocrystalline Iron Oxide, Cross-linked Iron Oxide (CLIO)-NH2 and tat-CLIO

Science.gov (United States)

Song, Miyeoun; Kim, Yunhee; Lim, Dongyeol; Song, In-Chan; Yoon, Byung-Woo

2007-01-01

Objective We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH2 and tat-CLIO. Materials and Methods The hNSCs (5 × 105 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 µg/ml of ferumoxides, MION or CLIO-NH2, and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. Results The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15 ± 0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH2, respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH2 into the hNSCs was comparable to that of tat-CLIO. Conclusion For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH2 and the transfection agent PLL. PMID:17923778

Milk peptides increase iron solubility in water but do not affect DMT-1 expression in Caco-2 cells

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In vitro digestion of milk produces peptide fractions that enhance iron uptake by Caco-2 cells. Our objectives were to investigate whether these fractions a) exert their effect by increasing relative gene expression of DMT-1 in Caco-2 cells b) enhance iron dialyzability when added in meals. Peptid...

Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

International Nuclear Information System (INIS)

Laskey, J.D.; Ponka, P.; Schulman, H.M.

1986-01-01

In many types of cells the synthesis of σ-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from 125 I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or 59 Fe-Tf (20 μM). Furthermore, in induced Friend cells 100 μM Fe-SIH stimulated 2- 14 C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells

Central role for ferritin in the day/night regulation of iron homeostasis in marine phytoplankton

Science.gov (United States)

Botebol, Hugo; Lesuisse, Emmanuel; Šuták, Robert; Six, Christophe; Lozano, Jean-Claude; Schatt, Philippe; Vergé, Valérie; Kirilovsky, Amos; Morrissey, Joe; Léger, Thibaut; Camadro, Jean-Michel; Gueneugues, Audrey; Bowler, Chris; Blain, Stéphane; Bouget, François-Yves

2015-01-01

In large regions of the open ocean, iron is a limiting resource for phytoplankton. The reduction of iron quota and the recycling of internal iron pools are among the diverse strategies that phytoplankton have evolved to allow them to grow under chronically low ambient iron levels. Phytoplankton species also have evolved strategies to cope with sporadic iron supply such as long-term storage of iron in ferritin. In the picophytoplanktonic species Ostreococcus we report evidence from observations both in the field and in laboratory cultures that ferritin and the main iron-binding proteins involved in photosynthesis and nitrate assimilation pathways show opposite diurnal expression patterns, with ferritin being maximally expressed during the night. Biochemical and physiological experiments using a ferritin knock-out line subsequently revealed that this protein plays a central role in the diel regulation of iron uptake and recycling and that this regulation of iron homeostasis is essential for cell survival under iron limitation. PMID:26553998

Regulation of transepithelial transport of iron by hepcidin

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NATALIA P MENA

2006-01-01

Full Text Available Hepcidin (Hepc is a 25 amino acid cationic peptide with broad antibacterial and antifungal actions. A likely role for Hepc in iron metabolism was suggested by the observation that mice having disruption of the gene encoding the transcription factor USF2 failed to produce Hepc mRNA and developed spontaneous visceral iron overload. Lately, Hepc has been considered the "stores regulator," a putative factor that signals the iron content of the body to intestinal cells. In this work, we characterized the effect of Hepc produced by hepatoma cells on iron absorption by intestinal cells. To that end, human Hepc cDNA was cloned and overexpressed in HepG2 cells and conditioned media from Hepc-overexpressing cells was used to study the effects of Hepc on intestinal Caco-2 cells grown in bicameral inserts. The results indicate that Hepc released by HepG2 inhibited apical iron uptake by Caco-2 cells, probably by inhibiting the expression of the apical transporter DMT1. These results support a model in which Hepc released by the liver negatively regulates the expression of transporter DMT1 in the enterocyte

Analysis of a Ferric Uptake Regulator (Fur) Mutant ofDesulfovibrio vulgaris Hildenborough

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Bender, Kelly S.; Yen, Huei-Che Bill; Hemme, Christopher L.; Yang, Zamin K.; He, Zhili; He, Qiang; Zhou, Jizhong; Huang, Katherine H.; Alm, Eric J.; Hazen, Terry C.; Arkin, Adam P.; Wall, Judy D.

2007-09-21

Previous experiments examining the transcriptional profileof the anaerobe Desulfovibrio vulgaris demonstrated up-regulation of theFur regulon in response to various environmental stressors. To test theinvolvement of Fur in the growth response and transcriptional regulationof D. vulgaris, a targeted mutagenesis procedure was used for deletingthe fur gene. Growth of the resulting ?fur mutant (JW707) was notaffected by iron availability, but the mutant did exhibit increasedsensitivity to nitrite and osmotic stresses compared to the wild type.Transcriptional profiling of JW707 indicated that iron-bound Fur acts asa traditional repressor for ferrous iron uptake genes (feoAB) and othergenes containing a predicted Fur binding site within their promoter.Despite the apparent lack of siderophore biosynthesis genes within the D.vulgaris genome, a large 12-gene operon encoding orthologs to TonB andTolQR also appeared to be repressed by iron-bound Fur. While other genespredicted to be involved in iron homeostasis were unaffected by thepresence or absence of Fur, alternative expression patterns that could beinterpreted as repression or activation by iron-free Fur were observed.Both the physiological and transcriptional data implicate a globalregulatory role for Fur in the sulfate-reducing bacterium D.vulgaris.

The interplay between siderophore secretion and coupled iron and copper transport in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120.

Science.gov (United States)

Nicolaisen, Kerstin; Hahn, Alexander; Valdebenito, Marianne; Moslavac, Suncana; Samborski, Anastazia; Maldener, Iris; Wilken, Corinna; Valladares, Ana; Flores, Enrique; Hantke, Klaus; Schleiff, Enrico

2010-11-01

Iron uptake is essential for Gram-negative bacteria including cyanobacteria. In cyanobacteria, however, the iron demand is higher than in proteobacteria due to the function of iron as a cofactor in photosynthesis and nitrogen fixation, but our understanding of iron uptake by cyanobacteria stands behind the knowledge in proteobacteria. Here, two genes involved in this process in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 were identified. ORF all4025 encodes SchE, a putative cytoplasmic membrane-localized transporter involved in TolC-dependent siderophore secretion. Inactivation of schE resulted in an enhanced sensitivity to high metal concentrations and decreased secretion of hydroxamate-type siderophores. ORF all4026 encodes a predicted outer membrane-localized TonB-dependent iron transporter, IacT. Inactivation of iacT resulted in decreased sensitivity to elevated iron and copper levels. Expression of iacT from the artificial trc promoter (P(trc)) resulted in sensitization against tested metals. Further analysis showed that iron and copper effects are synergistic because a decreased supply of iron induced a significant decrease of copper levels in the iacT insertion mutant but an increase of those levels in the strain carrying P(trc)-iacT. Our results unravel a link between iron and copper homeostasis in Anabaena sp. PCC 7120. Copyright © 2010 Elsevier B.V. All rights reserved.

Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells

International Nuclear Information System (INIS)

Chen Haobin; Davidson, Todd; Singleton, Steven; Garrick, Michael D.; Costa, Max

2005-01-01

Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1α). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic

The Small Protein HemP Is a Transcriptional Activator for the Hemin Uptake Operon in Burkholderia multivorans ATCC 17616.

Science.gov (United States)

Sato, Takuya; Nonoyama, Shouta; Kimura, Akane; Nagata, Yuji; Ohtsubo, Yoshiyuki; Tsuda, Masataka

2017-08-15

Iron and heme play very important roles in various metabolic functions in bacteria, and their intracellular homeostasis is maintained because high concentrations of free forms of these molecules greatly facilitate the Fenton reaction-mediated production of large amounts of reactive oxygen species that severely damage various biomolecules. The ferric uptake regulator (Fur) from Burkholderia multivorans ATCC 17616 is an iron-responsive global transcriptional regulator, and its fur deletant exhibits pleiotropic phenotypes. In this study, we found that the phenotypes of the fur deletant were suppressed by an additional mutation in hemP The transcription of hemP was negatively regulated by Fur under iron-replete conditions and was constitutive in the fur deletant. Growth of a hemP deletant was severely impaired in a medium containing hemin as the sole iron source, demonstrating the important role of HemP in hemin utilization. HemP was required as a transcriptional activator that specifically binds the promoter-containing region upstream of a Fur-repressive hmuRSTUV operon, which encodes the proteins for hemin uptake. A hmuR deletant was still able to grow using hemin as the sole iron source, albeit at a rate clearly lower than that of the wild-type strain. These results strongly suggested (i) the involvement of HmuR in hemin uptake and (ii) the presence in ATCC 17616 of at least part of other unknown hemin uptake systems whose expression depends on the HemP function. Our in vitro analysis also indicated high-affinity binding of HemP to hemin, and such a property might modulate transcriptional activation of the hmu operon. IMPORTANCE Although the hmuRSTUV genes for the utilization of hemin as a sole iron source have been identified in a few Burkholderia strains, the regulatory expression of these genes has remained unknown. Our analysis in this study using B. multivorans ATCC 17616 showed that its HemP protein is required for expression of the hmuRSTUV operon, and the

A critical look at the calculation of the binding characteristics and concentration of iron complexing ligands in seawater with suggested improvements

NARCIS (Netherlands)

Gerringa, L.J.A.; Rijkenberg, M.J.A.; Thuróczy, C.-E.; Maas, L.R.M.

2014-01-01

Environmental context
The low concentration of iron in the oceans limits growth of phytoplankton. Dissolved organic molecules, called ligands, naturally present in seawater, bind iron thereby increasing its solubility and, consequently, its availability for biological uptake by phytoplankton. The

Intraarticular application of superparamagnetic nanoparticles and their uptake by synovial membrane-an experimental study in sheep

Energy Technology Data Exchange (ETDEWEB)

Schulze, Katja [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich (Switzerland); Koch, Annette [Department of Chemistry and Applied BioSciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Winterthurerstrasse 190, 8057 Zurich (Switzerland); Schoepf, Bernhard [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich (Switzerland); Petri, Alke [Laboratory of Powder Technology, Swiss Federal Institute of Technology (EPFL), Lausanne (Switzerland); Steitz, Benedikt [Laboratory of Powder Technology, Swiss Federal Institute of Technology (EPFL), Lausanne (Switzerland); Chastellain, Mathieu [Laboratory of Powder Technology, Swiss Federal Institute of Technology (EPFL), Lausanne (Switzerland); Hofmann, Margarethe [MatSearch, Chemin Jean Pavillard 14, 1009 Pully (Switzerland); Hofmann, Heinrich [Laboratory of Powder Technology, Swiss Federal Institute of Technology (EPFL), Lausanne (Switzerland); Rechenberg, Brigitte von [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich (Switzerland)]. E-mail: bvonrechenberg@vetclinics.unizh.ch

2005-05-15

A superparamagnetic iron oxide nanoparticle, coated with polyvinyl alcohol (PVA-SPION) and its fluorescently functionalized analogue (amino-PVA-Cy3.5-SPION) were compared in vivo as proof of principle for future use in magnetic drug targeting in inflammatory joint diseases. They were injected either intraarticularly or periarticularly and their uptake by cells of the synovial membrane was evaluated. Uptake was completed in 48 h and was enforced by an extracorporally applied magnet.

Intraarticular application of superparamagnetic nanoparticles and their uptake by synovial membrane-an experimental study in sheep

International Nuclear Information System (INIS)

Schulze, Katja; Koch, Annette; Schoepf, Bernhard; Petri, Alke; Steitz, Benedikt; Chastellain, Mathieu; Hofmann, Margarethe; Hofmann, Heinrich; Rechenberg, Brigitte von

2005-01-01

A superparamagnetic iron oxide nanoparticle, coated with polyvinyl alcohol (PVA-SPION) and its fluorescently functionalized analogue (amino-PVA-Cy3.5-SPION) were compared in vivo as proof of principle for future use in magnetic drug targeting in inflammatory joint diseases. They were injected either intraarticularly or periarticularly and their uptake by cells of the synovial membrane was evaluated. Uptake was completed in 48 h and was enforced by an extracorporally applied magnet

Examination and Elimination of Defects in Cone Casting Made of Ductile Cast Iron

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Guzik E.

2013-12-01

Full Text Available In the scope of existing cooperation with the Foundry of Cast Iron ZM “WSK Rzeszów” Ltd. there was carried out research work of microstructure and mechanical properties in the walls of a cone casting made of ductile cast iron. The particular attention was being put to the search of the potential brittle phases which have deleterious effect on ductility and dynamic properties of highly strained use of the casting prone to the potential risk of cracks during the highly strained use.

Fob1 and Fob2 proteins are virulence determinants of Rhizopus oryzae via facilitating iron uptake from ferrioxamine

Science.gov (United States)

Dialysis patients with chronic renal failure receiving deferoxamine for treating iron overload are uniquely predisposed for mucormycosis. Although not secreted by Mucorales, previous studies established that Rhizopus species utilize iron from ferrioxamine (iron-rich form of deferoxamine). Here we de...

Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

Science.gov (United States)

Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

2016-10-03

FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

Roles of iron in the survival, growth, and pathogenesis of Legionella pneumophila

International Nuclear Information System (INIS)

Quinn, F.D.

1985-01-01

The essentially of iron for living cells has long been recognized, and the availability of host-iron has been proposed as a contributing factor to virulence in bacterial, fungal, and protozoan infections. The mechanism by which legionella pneumophila causes disease is unknown. Growth of fresh clinical or environmental isolates in pure culture requires 20 times more iron than is needed for most other bacteria. Thus, increased plasma iron levels may be needed for multiplication within human hosts. It was observed that: (1) this organism can be more readily deprived of iron by iron binding agents than all other bacteria studied, and this inhibition can be reversed by the addition of iron; (2) normal human blood serum kills L. pneumophila and the bactericidal action is decreased when complement is inactivated or enough iron to saturate serum transferrin is added to the system; (3) in assays with a radioactive isotope of iron ( 55 Fe), no specific iron sequestering system was detected; (4) in analysis of outer membrane proteins with 55 Fe, SDS-polyacrylamide gel electrophoresis, and autoradiography, no specific outer membrane proteins responsible for iron acquisition were observed; and (5) in assays for protease, iron does not stimulate production of extracellular proteases. These observations indicate that L. pneumophila has no specific iron uptake mechanism, but instead relies on passive diffusion and/or non-specific mechanisms to obtain its iron

Almond milk fermented with different potentially probiotic bacteria improves iron uptake by intestinal epithelial (Caco-2 cells

Directory of Open Access Journals (Sweden)

Neus Bernat

2015-04-01

Full Text Available New fermented almond milks were developed, using different potentially probiotic bacteria, in order to meet the current demand for healthy, versatile non-dairy products. An in vitro digestion/Caco-2 cell model was used to evaluate the effect of both non-fermented and fermented almond milks on the mitochondrial enzymatic activities of enterocytes. Moreover, macrophages were challenged with the in-vitro digested samples and the production of pro-inflammatory biomarkers TNF-a and IL-6 was quantified. Enzymatic activities of cell cultures seemed to be stimulated by the exposure to both fermented and non-fermented almond milks. Both biomarkers decreased (p< 0.05 in fermented almond milks with either B. bifidum or B. longum. Results showed that fermented almond products favored the energetic metabolism of enterocytes and had a lower inflammatory response than non-fermented almond milk, suggesting its benefits for the management of allergies/intolerances. Moreover, the fermentation process enhanced the uptake of iron by Caco-2 cells, especially when using L. rhamnosus and either B. bifidum or B. longum as starters, thus improving the product bioactivity. Therefore, new non-dairy fermented products with functional properties were developed, which might be positioned as alternatives to cow-milk products for sensitized groups of population (allergic and/or intolerant to cow milk or anemic population, among others.

The effects of dietary iron concentration on gastrointestinal and branchial assimilation of both iron and cadmium in zebrafish (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Cooper, C.A. [Division of Health and Life Sciences, King' s College London, 150 Stamford Street, London SE1 9NN (United Kingdom)]. E-mail: chris.cooper@ex.ac.uk; Handy, R.D. [School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom); Bury, N.R. [Division of Health and Life Sciences, King' s College London, 150 Stamford Street, London SE1 9NN (United Kingdom)

2006-08-23

Zebrafish (Danio rerio) were fed either a diet containing 33 mg Fe kg{sup -1} (low) or 95 mg Fe kg{sup -1} (normal) for 10 weeks, after which short-term Cd and Fe uptake by the gastrointestinal tract and gill was assessed. Carcass metal content and transcript levels of the iron importer, Divalent Metal Transporter 1 (DMT1) and an iron exporter, ferroportin1, in both the gastrointestinal tract and gill were also measured. Fish fed the low Fe diet accumulated 13 times more Cd into their livers via the gastrointestinal tract than those fed the normal Fe diet. However, no significant increase in liver Fe accumulation was measured. Concomitantly, when exposed to 48 nmol Cd L{sup -1} fish fed the low Fe diet exhibited a {approx}4-fold increase in Cd accumulation on the gill and in the liver, compared to those fed a normal diet. In addition, fish fed the low Fe diet also significantly accumulated more Fe on the gill (nine-fold increase) and into the carcass (four-fold increase) when exposed to 96 nmol Fe L{sup -1}, compared to fish fed a normal diet. Surprisingly, carcass Fe, Ca and Mg concentrations were increased in fish fed the low Fe diet, which suggests that Fe body levels may not be a good indicator of whether a fish is more or less susceptible to increased non-essential metal accumulation via an Fe uptake pathway. However, significantly elevated transcript levels of DMT1 and ferroportin1 (2.7- and 3.8-fold induction, respectively) were seen in the gastrointestinal tract, and DMT1 in the gills (1.8-fold induction) of zebrafish fed a low Fe diet. The correlation between Cd uptake and DMT1 expression suggests that one route of uptake of Cd, either from the diet or from the water, could be via DMT1.

Iron forms in some egyptian soils

International Nuclear Information System (INIS)

EL Kholi, A.F.; Massoud, M.A.; EL-Naggar, H.A.; Gadallah, A.

1990-01-01

The present study is an attempt to find out the available forms of iron (Fe 2+ and Fe 3+ ) in five egyptian soils samples, representing alluvial, calcareous and sandy soils. Concerning the iron content of soil either Fe 2+ or Fe 3+ , the tested soil types were relatively arranged in the order alluvial> calcareous> sandy soil. In spite of the considerable variations in the soil content of iron cations, the Fe 2+ /Fe 3+ ratio was almost kept constant around 0.83. The uniformity of the ferrous : ferric ratio in the different tested soil types indicates their similarity in their redox-potential, pH and their environmental conditions, particularly, the aeration and partial O 2 - pressure degree. Fe 2+ /Fe 3+ being less than unity suggests that the Fe 2+ Fe 3+ reaction tends towards the forward direction, i.e., to the Fe 3+ formation. As a result of the pot experiment, significant correlations have been found between the laboratory determined soil Fe 2+ and both of the plant Fe-uptake and the plant dry matter weight

Oxidized Carbo-Iron causes reduced reproduction and lower tolerance of juveniles in the amphipod Hyalella azteca

Energy Technology Data Exchange (ETDEWEB)

Weil, Mirco, E-mail: m.weil@ect.de [ECT Oekotoxikologie GmbH, Böttgerstrasse 2-14, 65439 Flörsheim (Germany); Meißner, Tobias, E-mail: tmeiss@gmx.net [Fraunhofer Institute for Ceramic Technologies and Systems, Winterbergstrasse 28, 01277 Dresden (Germany); Springer, Armin, E-mail: armin.springer@nano.tu-dresden.de [Dresden University of Technology, Budapesterstrasse 27, 01069 Dresden (Germany); Bundschuh, Mirco, E-mail: mirco.bundschuh@slu.se [Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, Uppsala (Sweden); Institute for Environmental Sciences, University of Koblenz-Landau, Forststrasse 7, 76829 Landau (Germany); Hübler, Lydia, E-mail: lydia.huebler@gmail.com [ECT Oekotoxikologie GmbH, Böttgerstrasse 2-14, 65439 Flörsheim (Germany); Schulz, Ralf, E-mail: schulz@uni-landau.de [Institute for Environmental Sciences, University of Koblenz-Landau, Forststrasse 7, 76829 Landau (Germany); Duis, Karen, E-mail: k-duis@ect.de [ECT Oekotoxikologie GmbH, Böttgerstrasse 2-14, 65439 Flörsheim (Germany)

2016-12-15

Highlights: • Effects on growth, reproduction and survival at ≥12.5 mg of oxidized Carbo-Iron/L were studied. • Carbo-Iron significantly increases sensitivity of offspring from exposed amphipods. • Toxicity is most likely mediated by an impaired uptake of nutrients and energy. - Abstract: For in situ remediation of groundwater contaminated by halogenated hydrocarbons Carbo-Iron{sup ®}, a composite of microscale activated carbon and nano Fe{sup 0}, was developed. Against the background of intended release of Carbo-Iron into the environment in concentrations in the g/L-range, potential ecotoxicological consequences were evaluated in the present study. The nano Fei{sup 0} in Carbo-Iron acts as reducing agent and is oxidized in aqueous systems by chlorinated solvents, groundwater constituents (e.g. dissolved oxygen) and anaerobic corrosion. As Carbo-Iron is generally oxidized rapidly after application into the environment, the oxidized state is environmentally most relevant, and Carbo-Iron was used in its oxidized form in the ecotoxicological tests. The amphipod Hyalella azteca was selected as a surrogate test species for functionally important groundwater crustaceans. Effects of Carbo-Iron on H. azteca were determined in a 10-d acute test, a 7-d feeding activity test and a 42-d chronic test. Additionally, a 56-d life cycle test was performed with a modified design to further evaluate effects of Carbo-Iron on adult H. azteca and their offspring. The size of Carbo-Iron particles in stock and test suspensions was determined via dynamic light scattering. Potential uptake of particles into test organisms was investigated using transmission and scanning electron microscopy. At the termination of the feeding and acute toxicity test (i.e. after 7 and 10 d of exposure, respectively), Carbo-Iron had a significant effect on the weight, length and feeding rate of H. azteca at the highest test concentration of 100 mg/L. While an uptake of Carbo-Iron into the gut was

Extraosseous radiotracer uptake on bone scan in beta-thalassemia: report of one case; Fixation extraosseuse du radiotraceur lors de la realisation d'une scintigraphie du squelette chez un patient atteint de beta-thalassemie: a propos d'un cas

Energy Technology Data Exchange (ETDEWEB)

Guezguez, M.; Nouira, M.; Sfar, R.; Chatti, K.; Ben Fradj, M.; Ben Ali, K.; Ajmi, S.; Essabbah, H. [CHU Sahloul, Service de Medecine Nucleaire, Sousse (Tunisia); Zrour, S. [EPS F. Bourguiba, Service de Rhumatologie, Monastir (Tunisia)

2009-10-15

Red blood cell transfusion, main therapeutic modality of beta-thalassemia, leads to iron overload which may perturb several metabolic ways. The aim of this paper is to illustrate the uptake abnormalities observed on bone scan of thalassaemic patients and to discuss mechanisms of extraosseous accumulation of the radiopharmaceutical in this pathology. We report a 16-year-old child suffering from beta-thalassemia major undergoing transfusion therapy. A bone scan was indicated to look for osseous infection. This study revealed a little skeletal uptake and abnormal liver, splenic and renal accumulation. A repeat bone scan, performed three weeks later showed a better skeletal uptake which enabled the discovery of focal abnormalities and made the diagnostic easier. The effect of iron overload on radiopharmaceuticals uptake in bone scan is known since 1975. Dissociation of {sup 99m}Tc from the carrier ligand due to the presence of iron excess seems the most plausible hypothesis. Free {sup 99m}Tc can be bound to other tissular substrates which can explain extraosseous uptake. The normally available pool for bone is reduced and then the skeletal uptake decreased. This report limits considerably the sensitivity of the bone scan. A well-led iron chelation and eventually the use of diuretic drug may guarantee a better quality of bone scan images. (authors)

Ultrastructural and some functional changes in tumor cells treated with stabilized iron oxide nanoparticles.

Science.gov (United States)

Yurchenko, O V; Todor, I N; Khayetsky, I K; Tregubova, N A; Lukianova, N Yu; Chekhun, V F

2010-12-01

To study the ultrastructure and some functional indexes of tumor cells treated with stabilized iron nanoparticles in vitro. 3-[4,5dimethylthiazol-2-1]-2,5-diphenyltetrazolium bromide (MTT)-test, electron microscopy, polarography with applying of closed Clark's electrode. It was shown that cultivation of cells with stabilized Fe(3)O(4) leads to intracellular accumulation of ferromagnetic nanoparticles. The most active ferromagnetic uptake by cells has been observed after 24 and 48 h of incubation. The presence of ferromagnetic in cells led to altered mitochondrial structure that caused the decrease of oxygen uptake rate in the cells of all studied lines. Ferromagnetic released from the majority of cells via exocytosis or clasmacytosis after a certain period of time. The number of dead cells or cells with severe damage was moderate, so cytotoxic action of stabilized iron oxide nanoparticles was minimal toward the studied cell lines. the presence of ferromagnetic nanoparticles in culture medium led to alterations in mitochondria ultrastructural organization and decrease of oxygen uptake by mitochondria in sensitive and anticancer-drugs resistant cells.

Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung-Min [Department of Biological Sciences, University of Columbia, NY (United States); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Attieh, Zouhair K. [Department of Laboratory Science and Technology, American University of Science and Technology, Ashrafieh (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Son, Hee Sook [Department of Food Science and Human Nutrition, College of Human Ecology, Chonbuk National University (Korea, Republic of); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Chen, Huijun [Medical School, Nanjing University, Nanjing 210008, Jiangsu Province (China); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Bacouri-Haidar, Mhenia [Department of Biology, Faculty of Sciences (I), Lebanese University, Hadath (Lebanon); Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States); Vulpe, Chris D., E-mail: vulpe@berkeley.edu [Department of Nutritional Science and Toxicology, University of California, Berkeley, CA (United States)

2012-05-11

Highlights: Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in non-polarized cells. Black-Right-Pointing-Pointer Hephaestin localizes in the perinuclear space in iron deficient and polarized cells. Black-Right-Pointing-Pointer Hephaestin with apical iron moves near to basolateral membrane of polarized cells. Black-Right-Pointing-Pointer Peri-basolateral location of hephaestin is accessible to the extracellular space. Black-Right-Pointing-Pointer Hephaestin is involved in iron mobilization from the intestine to circulation. -- Abstract: While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO{sub 4}) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a

Uranium uptake by hydroponically cultivated crop plants

Energy Technology Data Exchange (ETDEWEB)

Soudek, Petr; Petrova, Sarka [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic); Benesova, Dagmar [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic); Faculty of Environment Technology, Institute of Chemical Technology, Technicka 5, 166 28 Prague 6 (Czech Republic); Dvorakova, Marcela [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic); Vanek, Tomas, E-mail: vanek@ueb.cas.cz [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic)

2011-06-15

Hydroponicaly cultivated plants were grown on medium containing uranium. The appropriate concentrations of uranium for the experiments were selected on the basis of a standard ecotoxicity test. The most sensitive plant species was determined to be Lactuca sativa with an EC{sub 50} value about 0.1 mM. Cucumis sativa represented the most resistant plant to uranium (EC{sub 50} = 0.71 mM). Therefore, we used the uranium in a concentration range from 0.1 to 1 mM. Twenty different plant species were tested in hydroponic solution supplemented by 0.1 mM or 0.5 mM uranium concentration. The uranium accumulation of these plants varied from 0.16 mg/g DW to 0.011 mg/g DW. The highest uranium uptake was determined for Zea mays and the lowest for Arabidopsis thaliana. The amount of accumulated uranium was strongly influenced by uranium concentration in the cultivation medium. Autoradiography showed that uranium is mainly localized in the root system of the plants tested. Additional experiments demonstrated the possibility of influencing the uranium uptake from the cultivation medium by amendments. Tartaric acid was able to increase uranium uptake by Brassica oleracea and Sinapis alba up to 2.8 times or 1.9 times, respectively. Phosphate deficiency increased uranium uptake up to 4.5 times or 3.9 times, respectively, by Brassica oleracea and S. alba. In the case of deficiency of iron or presence of cadmium ions we did not find any increase in uranium accumulation. - Highlights: > The uranium accumulation in twenty different plant species varied from 0.160 to 0.011 mg/g DW. > Uranium is mainly localized in the root system. > Tartaric acid was able to increase uranium uptake by Brassica oleracea and Sinapis alba. > The phosphates deficiency increase the uranium uptake.

Uranium uptake by hydroponically cultivated crop plants

International Nuclear Information System (INIS)

Soudek, Petr; Petrova, Sarka; Benesova, Dagmar; Dvorakova, Marcela; Vanek, Tomas

2011-01-01

Hydroponicaly cultivated plants were grown on medium containing uranium. The appropriate concentrations of uranium for the experiments were selected on the basis of a standard ecotoxicity test. The most sensitive plant species was determined to be Lactuca sativa with an EC 50 value about 0.1 mM. Cucumis sativa represented the most resistant plant to uranium (EC 50 = 0.71 mM). Therefore, we used the uranium in a concentration range from 0.1 to 1 mM. Twenty different plant species were tested in hydroponic solution supplemented by 0.1 mM or 0.5 mM uranium concentration. The uranium accumulation of these plants varied from 0.16 mg/g DW to 0.011 mg/g DW. The highest uranium uptake was determined for Zea mays and the lowest for Arabidopsis thaliana. The amount of accumulated uranium was strongly influenced by uranium concentration in the cultivation medium. Autoradiography showed that uranium is mainly localized in the root system of the plants tested. Additional experiments demonstrated the possibility of influencing the uranium uptake from the cultivation medium by amendments. Tartaric acid was able to increase uranium uptake by Brassica oleracea and Sinapis alba up to 2.8 times or 1.9 times, respectively. Phosphate deficiency increased uranium uptake up to 4.5 times or 3.9 times, respectively, by Brassica oleracea and S. alba. In the case of deficiency of iron or presence of cadmium ions we did not find any increase in uranium accumulation. - Highlights: → The uranium accumulation in twenty different plant species varied from 0.160 to 0.011 mg/g DW. → Uranium is mainly localized in the root system. → Tartaric acid was able to increase uranium uptake by Brassica oleracea and Sinapis alba. → The phosphates deficiency increase the uranium uptake.

Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

Science.gov (United States)

Chen, Eunice Y.; Hodge, Sasson; Tai, Katherine; Hou, Huagang; Khan, Nadeem; Hoopes, P. Jack; Samkoe, Kimberley S.

2013-02-01

Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.

Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis.

Science.gov (United States)

Metzendorf, Christoph; Zeigerer, Anja; Seifert, Sarah; Sparla, Richard; Najafi, Bahar; Canonne-Hergaux, François; Zerial, Marino; Muckenthaler, Martina U

2017-06-22

Liver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool.

RGD-conjugated iron oxide magnetic nanoparticles for magnetic resonance imaging contrast enhancement and hyperthermia.

Science.gov (United States)

Zheng, S W; Huang, M; Hong, R Y; Deng, S M; Cheng, L F; Gao, B; Badami, D

2014-03-01

The purpose of this study was to develop a specific targeting magnetic nanoparticle probe for magnetic resonance imaging and therapy in the form of local hyperthermia. Carboxymethyl dextran-coated ultrasmall superparamagnetic iron oxide nanoparticles with carboxyl groups were coupled to cyclic arginine-glycine-aspartic peptides for integrin α(v)β₃ targeting. The particle size, magnetic properties, heating effect, and stability of the arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide were measured. The arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide demonstrates excellent stability and fast magneto-temperature response. Magnetic resonance imaging signal intensity of Bcap37 cells incubated with arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide was significantly decreased compared with that incubated with plain ultrasmall superparamagnetic iron oxide. The preferential uptake of arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide by target cells was further confirmed by Prussian blue staining and confocal laser scanning microscopy.

Iron plaque formed under aerobic conditions efficiently immobilizes arsenic in Lupinus albus L roots.

Science.gov (United States)

Fresno, Teresa; Peñalosa, Jesús M; Santner, Jakob; Puschenreiter, Markus; Prohaska, Thomas; Moreno-Jiménez, Eduardo

2016-09-01

Arsenic is a non-threshold carcinogenic metalloid. Thus, human exposure should be minimised, e.g. by chemically stabilizing As in soil. Since iron is a potential As immobiliser, it was investigated whether root iron plaque, formed under aerobic conditions, affects As uptake, metabolism and distribution in Lupinus albus plants. White lupin plants were cultivated in a continuously aerated hydroponic culture containing Fe/EDDHA or FeSO4 and exposed to arsenate (5 or 20 μM). Only FeSO4 induced surficial iron plaque in roots. LA-ICP-MS analysis accomplished on root sections corroborated the association of As to this surficial Fe. Additionally, As(V) was the predominant species in FeSO4-treated roots, suggesting less efficient As uptake in the presence of iron plaque. Fe/EDDHA-exposed roots neither showed such surficial FeAs co-localisation nor As(V) accumulation; in contrast As(III) was the predominant species in root tissue. Furthermore, FeSO4-treated plants showed reduced shoot-to-root As ratios, which were >10-fold lower compared to Fe/EDDHA treatment. Our results highlight the role of an iron plaque formed in roots of white lupin under aerobic conditions on As immobilisation. These findings, to our knowledge, have not been addressed before for this plant and have potential implications on soil remediation (phytostabilisation) and food security (minimising As in crops). Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential of Phytase-Mediated Iron Release from Cereal-Based Foods: A Quantitative View

Science.gov (United States)

Nielsen, Anne V. F.; Tetens, Inge; Meyer, Anne S.

2013-01-01

The major part of iron present in plant foods such as cereals is largely unavailable for direct absorption in humans due to complexation with the negatively charged phosphate groups of phytate (myo-inositol (1,2,3,4,5,6)-hexakisphosphate). Human biology has not evolved an efficient mechanism to naturally release iron from iron phytate complexes. This narrative review will evaluate the quantitative significance of phytase-catalysed iron release from cereal foods. In vivo studies have shown how addition of microbially derived phytases to cereal-based foods has produced increased iron absorption via enzyme-catalysed dephosphorylation of phytate, indicating the potential of this strategy for preventing and treating iron deficiency anaemia. Despite the immense promise of this strategy and the prevalence of iron deficiency worldwide, the number of human studies elucidating the significance of phytase-mediated improvements in iron absorption and ultimately in iron status in particularly vulnerable groups is still low. A more detailed understanding of (1) the uptake mechanism for iron released from partially dephosphorylated phytate chelates, (2) the affinity of microbially derived phytases towards insoluble iron phytate complexes, and (3) the extent of phytate dephosphorylation required for iron release from inositol phosphates is warranted. Phytase-mediated iron release can improve iron absorption from plant foods. There is a need for development of innovative strategies to obtain better effects. PMID:23917170

Iron exchange between transferrin molecules mediated by phosphate compounds and other cell metabolites.

Science.gov (United States)

Morgan, E H

1977-08-25

The ability of a large number of cellular metabolites to release iron from transferrin was investigated by measuring the rate at which they could mediate iron exchange between two types of transferrin. Rabbit transferrin labelled with 59Fe was incubated with human apotransferrin in the presence of the metabolites. After varying periods of incubation the human transferrin was separated from the rabbit transferrin by immunoprecipitation. GTP, 2,3-diphosphoglycerate, ATP, ADP and citrate produced the most rapid exchange of iron between the two types of transferrin, but many other compounds showed some degree of activity. Iron exchange mediated by the organic phosphates had the characteristics of a single first-order reaction and was sensitive to changes of incubation temperature and pH. The activation energy for the exchange reaction was approx. 13 kcal/mol. The rate of iron exchange from the oxalate - iron - transferrin complex was much lower than from bicarbonate - iron - transferrin. It is concluded that several organic phosphates have the capacity of releasing iron from transferrin. These compounds may represent the means by which the iron is released during the process of cellular uptake.

Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons.

Science.gov (United States)

Tao, Ling-Xue; Huang, Xiao-Tian; Chen, Yu-Ting; Tang, Xi-Can; Zhang, Hai-Yan

2016-11-01

Iron dyshomeostasis is one of the primary causes of neuronal death in Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a nutraceutical in the United Sates. Here, we investigated the protective effects of HupA against iron overload-induced injury in neurons. Rat cortical neurons were treated with ferric ammonium citrate (FAC), and cell viability was assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine triphosphate (ATP) assays were performed to assess mitochondrial function. The labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron uptake protein expression were measured to determine iron metabolism changes. The modified Ellman's method was used to evaluate AChE activity. HupA significantly attenuated the iron overload-induced decrease in neuronal cell viability. This neuroprotective effect of HupA occurred concurrently with a decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly blocked the upregulation of the LIP level and other aberrant iron metabolism changes induced by iron overload. Additionally, another specific AChE inhibitor, donepezil (Don), at a concentration that caused AChE inhibition equivalent to that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that were induced by excessive iron. We provide the first demonstration of the protective effects of HupA against iron overload-induced neuronal damage. This beneficial role of HupA may be attributed to its attenuation of oxidative stress and mitochondrial dysfunction and elevation of LIP, and these effects are not associated with its AChE-inhibiting effect.

59Fe uptake by Salmonella typhimurium strains of different epidemiological sources

International Nuclear Information System (INIS)

Rabsch, W.; Reissbrodt, R.

1985-01-01

All Salmonella typhimurium strains tested were able to use iron from transferrin. In buffered nutrient broth - poor in iron-content - the strains were tested in 59 FeCl 3 and 59 Fe-transferrin uptake in different growth phases. In the early log phase the strains are able to catch the 59 Fe 3+ in a very great amount as it is necessary for the growth. The content of 59 Fe per cell was in the late log phase reduced until to a value, which seen to be enough for growth. The acquisition of 59 Fe-transferrin between the early and late log phase tested by 4 S. typhimurium strains was different. (author)

LABILE IRON IN CELLS AND BODY FLUIDS . Physiology, Pathology and Pharmacology

Directory of Open Access Journals (Sweden)

Zvi Ioav Cabantchik

2014-03-01

Full Text Available In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI composition varies with metal concentration and substances with chelating groups but also with pH and the redox potential. Although physiologically in the lower µM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI levels are continually regulated by an iron-responsive machinery that balances iron uptake versus deposition into ferritin. However, LCI rises aberrantly in some cell types due to faulty cell utilization pathways or infiltration by pathological iron forms that are found in hemosiderotic plasma. As LCI attains pathological levels, it can catalyze reactive O species (ROS formation that, at particular threshold, can surpass cellular anti-oxidant capacities and seriously damage its constituents. While in normal plasma and interstitial fluids, virtually all iron is securely carried by circulating transferrin (that renders iron essentially non-labile, in systemic iron overload (IO, the total plasma iron binding capacity is often surpassed by a massive iron influx from hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As plasma transferrin approaches iron saturation, labile plasma iron (LPI emerges in forms that can infiltrate cells by unregulated routes and raise LCI to toxic levels. Despite the limited knowledge available on LPI speciation in different types and degrees of iron overload, LPI measurements can be and are in fact used for identifying systemic IO and for initiating/adjusting chelation regimens to attain full-day LPI protection. A recent application of labile iron assay is the detection of labile components in iv iron formulations per se as well as in plasma (LPI following parenteral iron

Sugars increase non-heme iron bioavailability in human epithelial intestinal and liver cells.

Directory of Open Access Journals (Sweden)

Tatiana Christides

Full Text Available Previous studies have suggested that sugars enhance iron bioavailability, possibly through either chelation or altering the oxidation state of the metal, however, results have been inconclusive. Sugar intake in the last 20 years has increased dramatically, and iron status disorders are significant public health problems worldwide; therefore understanding the nutritional implications of iron-sugar interactions is particularly relevant. In this study we measured the effects of sugars on non-heme iron bioavailability in human intestinal Caco-2 cells and HepG2 hepatoma cells using ferritin formation as a surrogate marker for iron uptake. The effect of sugars on iron oxidation state was examined by measuring ferrous iron formation in different sugar-iron solutions with a ferrozine-based assay. Fructose significantly increased iron-induced ferritin formation in both Caco-2 and HepG2 cells. In addition, high-fructose corn syrup (HFCS-55 increased Caco-2 cell iron-induced ferritin; these effects were negated by the addition of either tannic acid or phytic acid. Fructose combined with FeCl3 increased ferrozine-chelatable ferrous iron levels by approximately 300%. In conclusion, fructose increases iron bioavailability in human intestinal Caco-2 and HepG2 cells. Given the large amount of simple and rapidly digestible sugars in the modern diet their effects on iron bioavailability may have important patho-physiological consequences. Further studies are warranted to characterize these interactions.

Sorption of ferrous iron by EPS from the acidophilic bacterium Acidiphilium Sp.: A mechanism proposal

Energy Technology Data Exchange (ETDEWEB)

Tapia, J.M.; MuNoz, J.; Gonzlez, F.; Blazquez, M.L.; Ballester, A.

2016-07-01

The aim of this work was to assess the uptake of Fe(II) by extracellular polymeric substances (EPS) from the acidophilic bacterium Acidiphillium 3.2Sup(5). These EPS were extracted using EDTA. EPS of A. 3.2Sup(5) loaded in sorption tests with Fe(II), were characterized using the following experimental techniques: scanning electron microscopy (SEM) with energy dispersive X-ray microanalysis (EDX), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental results indicate that EPS adsorb ferrous iron according to Freundlich model with a metal sorption uptake of K = 1.14 mg1−1/n L1/n g−1 and a sorption intensity of 1/n = 1.26. In addition, ferrous iron sorption by EPS took place by preferential interaction with the carboxyl group which promotes the formation of ferrous iron oxalates (FeC2O4). Since the interaction reaction was reversible (Log K = 0.77 ± 0.33), that means that the cation sorption can be reversed at convenience. (Author)

Molecular evidence and physiological characterization of iron absorption in isolated enterocytes of rainbow trout (Oncorhynchus mykiss): Implications for dietary cadmium and lead absorption

International Nuclear Information System (INIS)

Kwong, Raymond W.M.; Andres, Jose A.; Niyogi, Som

2010-01-01

Recent studies suggested the probable involvement of an apical iron (Fe 2+ ) transporter, the divalent metal transporter-1 (DMT1), in the uptake of several divalent metals in fish. The present study examined the gastrointestinal expression of the DMT1 gene, and investigated the kinetics of Fe 2+ uptake and its interactions with cadmium and lead in isolated enterocytes of freshwater rainbow trout (Oncorhynchus mykiss). The expressions of two DMT1 isoforms (Nramp-β and -γ) were recorded along the entire gastrointestinal tract of fish as well as in the enterocytes. Fe 2+ uptake in isolated enterocytes was saturable and sensitive to the proton gradient and membrane potential, suggesting DMT1-mediated transport. Both cadmium and lead inhibited Fe 2+ uptake in isolated enterocytes in a concentration-dependent manner, and lead appeared to be a stronger inhibitor than cadmium. The kinetic characterization of Fe 2+ uptake revealed that the apparent affinity of uptake was significantly decreased (increased K m ) in the presence of either cadmium or lead, whereas the maximum uptake rate (J max ) remained unchanged-indicating that the interaction between Fe 2+ and cadmium or lead is competitive in nature. Overall, our study suggests that the uptake of dietary cadmium and lead may occur via the iron-transporting pathway in fish.

Mechanisms of Hg(II) uptake and methylation in methylating bacteria

Energy Technology Data Exchange (ETDEWEB)

Morel, Francois M. M. [Princeton Univ., NJ (United States). Geosciences

2016-10-14

The goal of this project was to understand the critical factors which control the availability and transport of Hg(II) into cells, a first step in the production of the neurotoxin, methylmercury. Specifically, this research focused on understanding the mechanism of bacterial mercury uptake and how mercury speciation affects the specificity and kinetics of mercury transport. Our research has shown that Hg(II) uptake in three different iron and sulfate-reducing proteobacteria occurs by the following mechanism (1) : Hg(II) uptake is an active transport process requiring energy, (2) it is dependent upon the structure of the Hg binding ligand, and (3) it is mediated by a heavy metal transporter such as one which transports the essential metal, Zn(II). In order to determine whether this mechanism extends to more diverse phylogenetic groups, we have begun examining Hg(II) uptake and bioavailability in two representative Hg methylating strains within the Firmicutes. These organisms have remarkably different membrane structures distinct from the Proteobacteria. Our results show low uptake rates in these two species of Firmicutes relative to the previously characterized Proteobacteria. This may explain the low methylation rates and yields observed in these organisms. Most surprisingly, however, these organisms appear to take up Hg(II) passively, as the addition of a protonophore failed to reduce Hg(II) uptake in these organisms. This is quite different to what has been observed previously for the Proteobacteria and suggests a different mechanism for Hg(II) uptake in the Firmicutes. We are continuing to understand and describe Hg(II) uptake in these organisms. A manuscript is expected to be submitted on this research in June 2016.

HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication.

Science.gov (United States)

Mehta, Kosha J; Farnaud, Sebastien; Patel, Vinood B

2017-10-01

In liver hepatocytes, the HFE gene regulates cellular and systemic iron homeostasis by modulating cellular iron-uptake and producing the iron-hormone hepcidin in response to systemic iron elevation. However, the mechanism of iron-sensing in hepatocytes remain enigmatic. Therefore, to study the effect of iron on HFE and hepcidin (HAMP) expressions under distinct extracellular and intracellular iron-loading, we examined the effect of holotransferrin treatment (1, 2, 5 and 8 g/L for 6 h) on intracellular iron levels, and mRNA expressions of HFE and HAMP in wild-type HepG2 and previously characterized iron-loaded recombinant-TfR1 HepG2 cells. Gene expression was analyzed by real-time PCR and intracellular iron was measured by ferrozine assay. Data showed that in the wild-type cells, where intracellular iron content remained unchanged, HFE expression remained unaltered at low holotransferrin treatments but was upregulated upon 5 g/L (p HFE and HAMP expressions were elevated only at low 1 g/L treatment (p HFE (p HFE mRNA was independently elevated by extracellular and intracellular iron-excess. Thus, it may be involved in sensing both, extracellular and intracellular iron. Repression of HAMP expression under simultaneous intracellular and extracellular iron-loading resembles non-hereditary iron-excess pathologies.

Exploring cellular uptake of iron oxide nanoparticles associated with rhodium citrate in breast cancer cells.

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Chaves, Natalia L; Estrela-Lopis, Irina; Böttner, Julia; Lopes, Cláudio Ap; Guido, Bruna C; de Sousa, Aparecido R; Báo, Sônia N

2017-01-01

Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite-rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line. MRC NPs uptake in breast cancer cells was more effective than in normal cells, with regard to both the amount of internalized material and the achievement of more strategic intracellular distribution. Moreover, this process occurred through a clathrin-dependent endocytosis pathway with different basal expression levels of this protein in the cell lines tested.

The dental public health implications of cosmetic dentistry: a scoping review of the literature.

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Doughty, J; Lala, R; Marshman, Z

2016-09-01

The popularity of cosmetic surgery has seen a rapid increase recently, with the trend mirrored in dentistry. The Department of Health expressed concerns about the potential for biological and psychosocial harm of these cosmetic procedures. Furthermore, the dental public health implications (DPH) of the growing uptake of cosmetic dental procedures have not been explored. Conduct a scoping review to explore the DPH implications of cosmetic dentistry and identify gaps for future research. A fivestage scoping review was conducted of studies identified using the search terms cosmetic AND dentistry. Data from the studies meeting the inclusion criteria were extracted, collated and summarised into themes. Fifty-seven papers met the inclusion criteria (11 cross-sectional studies, 10 literature reviews and 36 opinion pieces). The DPH implications were summarised into five emergent themes: dento-legal and ethical, marketing, psychosocial, biological and workforce. These themes revealed patients' increased expectations, expanding commercialisation of the profession, psychological risks to vulnerable patients, the iatrogenic consequences of invasive cosmetic dental procedures and workforce implications of the current trends. The scoping review found that existing literature on cosmetic dentistry is predominately anecdotal - professional opinions and discussions. Despite this, our findings demonstrated workforce training and governance implications due to increased demand for cosmetic dentistry. Further empirical research is needed to understand the DPH implications of the increasing demand and uptake of cosmetic dental procedures to guide evidence-based policy to safeguard patients and improve the quality of dental services. Copyright© 2016 Dennis Barber Ltd

The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

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Laftah, A.H.; Simpson, R.J.; Peters, T.J.; Raja, K.B.

2008-01-01

The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p < 0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p < 0.005, p < 0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p < 0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p < 0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p < 0.05, p < 0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p < 0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p < 0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p < 0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption

Bacterial Iron Uptake Pathways: Gates for the Import of Bactericide Compounds.

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Schalk, Isabelle J; Mislin, Gaëtan L A

2017-06-08

Bacterial resistance to most antibiotics in clinical use has reached alarming proportions. A challenge for modern medicine will be to discover new antibiotics or strategies to combat multidrug resistant bacteria, especially Gram-negative bacteria for which the situation is particularly critical. Vectorization of bactericide compounds by siderophores (iron chelators produced by bacteria) is a promising strategy able to considerably increase the efficacy of drugs. Such a Trojan horse strategy can also extend activity of specific Gram-positive antibiotics to Gram-negative bacteria.

Interaction of aromatic amines with iron oxides: implications for prebiotic chemistry.

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Shanker, Uma; Singh, Gurinder; Kamaluddin

2013-06-01

The interaction of aromatic amines (aniline, p-chloroaniline, p-toludine and p-anisidine) with iron oxides (goethite, akaganeite and hematite) has been studied. Maximum uptake of amines was observed around pH 7. The adsorption data obtained at neutral pH were found to follow Langmuir adsorption. Anisidine was found to be a better adsorbate probably due to its higher basicity. In alkaline medium (pH > 8), amines reacted on goethite and akaganeite to give colored products. Analysis of the products by GC-MS showed benzoquinone and azobenzene as the reaction products of aniline while p-anisidine afforded a dimer. IR analysis of the amine-iron oxide hydroxide adduct suggests that the surface acidity of iron oxide hydroxides is responsible for the interaction. The present study suggests that iron oxide hydroxides might have played a role in the stabilization of organic molecules through their surface activity and in prebiotic condensation reactions.

Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

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Hoopes, P. Jack; Petryk, Alicia A.; Tate, Jennifer A.; Savellano, Mark S.; Strawbridge, Rendall R.; Giustini, Andrew J.; Stan, Radu V.; Gimi, Barjor; Garwood, Michael

2013-02-01

The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3-10 fold range. Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an MRI technique which provides a

In situ functionalization and PEO coating of iron oxide nanocrystals using seeded emulsion polymerization.

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Kloust, Hauke; Schmidtke, Christian; Feld, Artur; Schotten, Theo; Eggers, Robin; Fittschen, Ursula E A; Schulz, Florian; Pöselt, Elmar; Ostermann, Johannes; Bastús, Neus G; Weller, Horst

2013-04-16

Herein we demonstrate that seeded emulsion polymerization is a powerful tool to produce multiply functionalized PEO coated iron oxide nanocrystals. Advantageously, by simple addition of functional surfactants, functional monomers, or functional polymerizable linkers-solely or in combinations thereof-during the seeded emulsion polymerization process, a broad range of in situ functionalized polymer-coated iron oxide nanocrystals were obtained. This was demonstrated by purposeful modulation of the zeta potential of encapsulated iron oxide nanocrystals and conjugation of a dyestuff. Successful functionalization was unequivocally proven by TXRF. Furthermore, the spatial position of the functional groups can be controlled by choosing the appropriate spacers. In conclusion, this methodology is highly amenable for combinatorial strategies and will spur rapid expedited synthesis and purposeful optimization of a broad scope of nanocrystals.

Siderophores mediate reduced and increased uptake of cadmium by Streptomyces tendae F4 and sunflower (Helianthus annuus), respectively.

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Dimkpa, C O; Merten, D; Svatos, A; Büchel, G; Kothe, E

2009-11-01

As a toxic metal, cadmium (Cd) affects microbial and plant metabolic processes, thereby potentially reducing the efficiency of microbe or plant-mediated remediation of Cd-polluted soil. The role of siderophores produced by Streptomyces tendae F4 in the uptake of Cd by bacteria and plant was investigated to gain insight into the influence of siderophores on Cd availability to micro-organisms and plants. The bacterium was cultured under siderophore-inducing conditions in the presence of Cd. The kinetics of siderophore production and identification of the siderophores and their metal-bound forms were performed using electrospray ionization mass spectrometry. Inductively coupled plasma spectroscopy was used to measure iron (Fe) and Cd contents in the bacterium and in sunflower plant grown in Cd-amended soil. Siderophores significantly reduced the Cd uptake by the bacterium, while supplying it with iron. Bacterial culture filtrates containing three hydroxamate siderophores secreted by S. tendae F4 significantly promoted plant growth and enhanced uptake of Cd and Fe by the plant, relative to the control. Furthermore, application of siderophores caused slightly more Cd, but similar Fe uptake, compared with EDTA. Bioinoculation with Streptomyces caused a dramatic increase in plant Fe content, but resulted only in slight increase in plant Cd content. It is concluded that siderophores can help reduce toxic metal uptake in bacteria, while simultaneously facilitating the uptake of such metals by plants. Also, EDTA is not superior to hydroxamate siderophores in terms of metal solubilization for plant uptake. The study showed that microbial processes could indirectly influence the availability and amount of toxic metals taken up from the rhizosphere of plants. Furthermore, although EDTA is used for chelator-enhanced phytoremediation, microbial siderophores would be ideal for this purpose.

Higher concentrations of nanoscale zero-valent iron (nZVI) in soil induced rice chlorosis due to inhibited active iron transportation

International Nuclear Information System (INIS)

Wang, Jie; Fang, Zhanqiang; Cheng, Wen; Yan, Xiaomin; Tsang, Pokeung Eric; Zhao, Dongye

2016-01-01

In this study, the effects of concentrations 0, 100, 250, 500, 750 and 1000 mg kg"−"1 of nanoscale zero-valent iron (nZVI) on germination, seedlings growth, physiology and toxicity mechanisms were investigated. The results showed that nZVI had no effect on germination, but inhibited the rice seedlings growth in higher concentrations (>500 mg kg"−"1 nZVI). The highest suppression rate of the length of roots and shoots reached 46.9% and 57.5%, respectively. The 1000mg kg"−"1 nZVI caused the highest suppression rates for chlorophyll and carotenoids, at 91.6% and 85.2%, respectively. In addition, the activity of antioxidant enzymes was altered by the translocation of nanoparticles and changes in active iron content. Visible symptoms of iron deficiency were observed at higher concentrations, at which the active iron content decreased 61.02% in the shoots, but the active iron content not decreased in roots. Interestingly, the total and available amounts of iron in the soil were not less than those in the control. Therefore, the plants iron deficiency was not caused by (i) deficiency of available iron in the soil and (ii) restraint of the absorption that plant takes in the available iron, while induced by (ⅲ) the transport of active iron from the root to the shoot was blocked. The cortex tissues were seriously damaged by nZVI which was transported from soil to the root, these were proved by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). This current study shows that the mechanism of iron deficiency in rice seedling was due to transport of active iron from the root to the shoot blocked, which was caused by the uptake of nZVI. - Highlights: • Higher concentrations of nZVI induced iron deficiency in rice seedlings visibly. • nZVI was taken in rice seedlings and transported form root to shoot. • The pathway of active iron transport from root to shoot was inhibited. • The cortex tissues

Expression of multidrug resistance efflux pump gene norA is iron responsive in Staphylococcus aureus.

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Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu; He, Chuan

2012-04-01

Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl(3) repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus.

PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

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Dan Cheng

Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

Genetic/metabolic effect of iron metabolism and rare anemias

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Clara Camaschella

2013-03-01

Full Text Available Advances in iron metabolism have allowed a novel classification of iron disorders and to identify previously unknown diseases. These disorders include genetic iron overload (hemochromatosis and inherited iron-related anemias, in some cases accompanied by iron overload. Rare inherited anemias may affect the hepcidin pathway, iron absorption, transport, utilization and recycling. Among the genetic iron-related anemias the most common form is likely the iron-refractory iron-deficiency anemia (IRIDA, due to mutations of the hepcidin inhibitor TMPRSS6 encoding the serine protease matriptase-2. IRIDA is characterized by hepcidin up-regulation, decrease iron absorption and macrophage recycling and by microcytic- hypochromic anemia, unresponsive to oral iron. High serum hepcidin levels may suggest the diagnosis, which requires demonstrating the causal TMPRSS6 mutations by gene sequencing. Other rare microcytic hypochromic anemias associated with defects of iron transport-uptake are the rare hypotransferrinemia, and DMT1 and STEAP3 mutations. The degree of anemia is variable and accompanied by secondary iron overload even in the absence of blood transfusions. This is due to the iron-deficient or expanded erythropoiesis that inhibits hepcidin transcription, increases iron absorption, through the erythroid regulator, as in untransfused beta-thalassemia. Sideroblastic anemias are due to decreased mitochondrial iron utilization for heme or sulfur cluster synthesis. Their diagnosis requires demonstrating ringed sideroblasts by Perl’s staining of the bone marrow smears. The commonest X-linked form is due to deltaamino- levulinic-synthase-2-acid (ALAS2 mutations. The recessive, more severe form, affects SLC25A38, which encodes a potential mitochondrial importer of glycine, an amino acid essential for ALA synthesis and thus results in heme deficiency. Two disorders affect iron/sulfur cluster biogenesis: deficiency of the ATP-binding cassette B7 (ABCB7 causes X

The long term tsunami impact: Evolution of iron speciation and major elements concentration in tsunami deposits from Thailand.

Science.gov (United States)

Kozak, Lidia; Niedzielski, Przemyslaw

2017-08-01

The article describes the unique studies of the chemical composition changes of new geological object (tsunami deposits in south Thailand - Andaman Sea Coast) during four years (2005-2008) from the beginning of formation of it (deposition of tsunami transported material, 26 December 2004). The chemical composition of the acid leachable fraction of the tsunami deposits has been studied in the scope of concentration macrocompounds - concentration of calcium, magnesium, iron, manganese and iron speciation - the occurrence of Fe(II), Fe(III) and non-ionic iron species described as complexed iron (Fe complex). The changes of chemical composition and iron speciation in the acid leachable fraction of tsunami deposits have been observed with not clear tendencies of changes direction. For iron speciation changes the transformation of the Fe complex to Fe(III) has been recorded with no significant changes of the level of Fe(II). Copyright © 2017 Elsevier Ltd. All rights reserved.

Acquisition of iron from transferrin regulates reticulocyte heme synthesis

International Nuclear Information System (INIS)

Ponka, P.; Schulman, H.M.

1985-01-01

Fe-salicylaldehyde isonicotinoylhydrazone (SIH), which can donate iron to reticulocytes without transferrin as a mediator, has been utilized to test the hypothesis that the rate of iron uptake from transferrin limits the rate of heme synthesis in erythroid cells. Reticulocytes take up 59 Fe from [ 59 Fe]SIH and incorporate it into heme to a much greater extent than from saturating concentrations of [ 59 Fe]transferrin. Also, Fe-SIH stimulates [2- 14 C]glycine into heme when compared to the incorporation observed with saturating levels of Fe-transferrin. In addition, delta-aminolevulinic acid does not stimulate 59 Fe incorporation into heme from either [ 59 Fe]transferrin or [ 59 Fe]SIH but does reverse the inhibition of 59 Fe incorporation into heme caused by isoniazid, an inhibitor of delta-aminolevulinic acid synthase. Taken together, these results suggest the hypothesis that some step(s) in the pathway of iron from extracellular transferrin to intracellular protoporphyrin limits the overall rate of heme synthesis in reticulocytes

SCOPE: a scorecard for osteoporosis in Europe.

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Kanis, J A; Borgström, F; Compston, J; Dreinhöfer, K; Nolte, E; Jonsson, L; Lems, W F; McCloskey, E V; Rizzoli, R; Stenmark, J

2013-01-01

The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. The scorecard for osteoporosis in Europe (SCOPE) is an independent project that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis. The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap). There was a marked difference in fracture risk among the EU27. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27, only a minority of patients at high risk receive treatment for osteoporosis even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. The scorecard will enable healthcare professionals and policy makers to assess their country's general approach to the disease and provide indicators to inform future provision of healthcare.

Molecular evidence and physiological characterization of iron absorption in isolated enterocytes of rainbow trout (Oncorhynchus mykiss): Implications for dietary cadmium and lead absorption

Energy Technology Data Exchange (ETDEWEB)

Kwong, Raymond W.M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK., S7N 5B3 (Canada); Andres, Jose A. [Department of Biology, University of Saskatchewan, Saskatoon, SK., S7N 5E2 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, SK., S7N 5E2 (Canada)

2010-09-01

Recent studies suggested the probable involvement of an apical iron (Fe{sup 2+}) transporter, the divalent metal transporter-1 (DMT1), in the uptake of several divalent metals in fish. The present study examined the gastrointestinal expression of the DMT1 gene, and investigated the kinetics of Fe{sup 2+} uptake and its interactions with cadmium and lead in isolated enterocytes of freshwater rainbow trout (Oncorhynchus mykiss). The expressions of two DMT1 isoforms (Nramp-{beta} and -{gamma}) were recorded along the entire gastrointestinal tract of fish as well as in the enterocytes. Fe{sup 2+} uptake in isolated enterocytes was saturable and sensitive to the proton gradient and membrane potential, suggesting DMT1-mediated transport. Both cadmium and lead inhibited Fe{sup 2+} uptake in isolated enterocytes in a concentration-dependent manner, and lead appeared to be a stronger inhibitor than cadmium. The kinetic characterization of Fe{sup 2+} uptake revealed that the apparent affinity of uptake was significantly decreased (increased K{sub m}) in the presence of either cadmium or lead, whereas the maximum uptake rate (J{sub max}) remained unchanged-indicating that the interaction between Fe{sup 2+} and cadmium or lead is competitive in nature. Overall, our study suggests that the uptake of dietary cadmium and lead may occur via the iron-transporting pathway in fish.

Mechanistic insights into a novel exporter-importer system of Mycobacterium tuberculosis unravel its role in trafficking of iron.

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Aisha Farhana

2008-05-01

Full Text Available Elucidation of the basic mechanistic and biochemical principles underlying siderophore mediated iron uptake in mycobacteria is crucial for targeting this principal survival strategy vis-à-vis virulence determinants of the pathogen. Although, an understanding of siderophore biosynthesis is known, the mechanism of their secretion and uptake still remains elusive.Here, we demonstrate an interplay among three iron regulated Mycobacterium tuberculosis (M.tb proteins, namely, Rv1348 (IrtA, Rv1349 (IrtB and Rv2895c in export and import of M.tb siderophores across the membrane and the consequent iron uptake. IrtA, interestingly, has a fused N-terminal substrate binding domain (SBD, representing an atypical subset of ABC transporters, unlike IrtB that harbors only the permease and ATPase domain. SBD selectively binds to non-ferrated siderophores whereas Rv2895c exhibits relatively higher affinity towards ferrated siderophores. An interaction between the permease domain of IrtB and Rv2895c is evident from GST pull-down assay. In vitro liposome reconstitution experiments further demonstrate that IrtA is indeed a siderophore exporter and the two-component IrtB-Rv2895c system is an importer of ferrated siderophores. Knockout of msmeg_6554, the irtA homologue in Mycobacterium smegmatis, resulted in an impaired M.tb siderophore export that is restored upon complementation with M.tb irtA.Our data suggest the interplay of three proteins, namely IrtA, IrtB and Rv2895c in synergizing the balance of siderophores and thus iron inside the mycobacterial cell.

Ocean iron fertilization in the context of the Kyoto protocol and the post-Kyoto process

International Nuclear Information System (INIS)

Bertram, Christine

2010-01-01

Ocean iron fertilization is currently discussed as a potential measure to mitigate climate change by enhancing oceanic CO 2 uptake. Its mitigation potential is not yet well explored, and carbon offsets generated through iron fertilization activities could currently not be traded on regulated carbon markets. Still, commercial interests in ocean iron fertilization already exist, which underlines the need to investigate a possible regulatory framework for it. To this end, I first discuss important basic aspects of ocean iron fertilization, namely its scientific background, quantitative potential, side effects, and costs. In a second step, I review regulatory aspects connected to ocean iron fertilization, like its legal status and open access issues. Moreover, I analyze how the regulations for afforestation and reforestation activities within the framework of the Kyoto Clean Development Mechanism (CDM) could be applied to ocean iron fertilization. Main findings are that the quantitative potential of ocean iron fertilization is limited, that costs are higher than initially hoped, and that potential adverse side effects are severe. Moreover, the legal status of ocean iron fertilization is currently not well defined, open access might cause inefficiencies, and the CDM regulations could not be easily applied to ocean iron fertilization.

Refinement of adsorptive coatings for fluorescent riboflavin-receptor-targeted iron oxide nanoparticles.

Science.gov (United States)

Tsvetkova, Yoanna; Beztsinna, Nataliia; Jayapaul, Jabadurai; Weiler, Marek; Arns, Susanne; Shi, Yang; Lammers, Twan; Kiessling, Fabian

2016-01-01

Flavin mononucleotide (FMN) is a riboflavin derivative that can be exploited to target the riboflavin transporters (RFTs) and the riboflavin carrier protein (RCP) in cells with high metabolic activity. In this study we present the synthesis of different FMN-coated ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) and their efficiency as targeting contrast agents. Since FMN alone cannot stabilize the nanoparticles, we used adenosine phosphates--AMP, ADP and ATP--as spacers to obtain colloidally stable nanoparticles. Nucleotides with di- and triphosphate groups were intended to increase the USPIO charge and thus improve zeta potential and stability. However, all nanoparticles formed negatively charged clusters with similar properties in terms of zeta potential (-28 ± 2 mV), relaxivity (228-259 mM(-1) s(-1) at 3 T) and hydrodynamic radius (53-85 nm). Molecules with a higher number of phosphate groups, such as ADP and ATP, have a higher adsorption affinity towards iron oxide, which, instead of providing more charge, led to partial desorption and replacement of FMN. Hence, we obtained USPIOs carrying different amounts of targeting agent, which significantly influenced the nanoparticles' uptake. The nanoparticles' uptake by different cancer cells and HUVECs was evaluated photometrically and with MR relaxometry, showing that the cellular uptake of the USPIOs increases with the FMN amount on their surface. Thus, for USPIOs targeted with riboflavin derivatives the use of spacers with increasing numbers of phosphate groups does not improve either zeta potential or the particles' stability, but rather detaches the targeting moieties from their surface, leading to lower cellular uptake. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles

International Nuclear Information System (INIS)

Brillet, P-Y.; Gazeau, F.; Luciani, A.; Bessoud, B.; Cuenod, C.-A.; Siauve, N.; Pons, J.-N.; Poupon, J.; Clement, O.

2005-01-01

This study was designed to compare tumor enhancement by superparamagnetic iron oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In vitro, relaxometry and media with increasing complexity were used to assess the changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with subcutaneously implanted tumors were imaged for 24 h after injection of particles to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo, our results with ferumoxtran showed an early T2 peak (1 h), suggesting intravascular particles and a second peak in T1 (12 h), suggesting intrainterstitial accumulation of particles. With AP, the late peak (24 h) suggested an intracellular accumulation of particles. In vitro, anionic iron oxide nanoparticles are suitable for cellular labeling due to a high cellular uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of tumors due to a favorable biodistribution. (orig.)

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

Science.gov (United States)

Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

2014-01-01

Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

Iron Supplementation during Three Consecutive Days of Endurance Training Augmented Hepcidin Levels

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Aya Ishibashi

2017-07-01

Full Text Available Iron supplementation contributes an effort to improving iron status among athletes, but it does not always prevent iron deficiency. In the present study, we explored the effect of three consecutive days of endurance training (twice daily on the hepcidin-25 (hepcidin level. The effect of iron supplementation during this period was also determined. Fourteen male endurance athletes were enrolled and randomly assigned to either an iron-treated condition (Fe condition, n = 7 or a placebo condition (Control condition; CON, n = 7. They engaged in two 75-min sessions of treadmill running at 75% of maximal oxygen uptake on three consecutive days (days 1–3. The Fe condition took 12 mg of iron twice daily (24 mg/day, and the CON condition did not. On day 1, both conditions exhibited significant increases in serum hepcidin and plasma interleukin-6 levels after exercise (p < 0.05. In the CON condition, the hepcidin level did not change significantly throughout the training period. However, in the Fe condition, the serum hepcidin level on day 4 was significantly higher than that of the CON condition (p < 0.05. In conclusion, the hepcidin level was significantly elevated following three consecutive days of endurance training when moderate doses of iron were taken.

Iron Supplementation during Three Consecutive Days of Endurance Training Augmented Hepcidin Levels.

Science.gov (United States)

Ishibashi, Aya; Maeda, Naho; Kamei, Akiko; Goto, Kazushige

2017-07-30

Iron supplementation contributes an effort to improving iron status among athletes, but it does not always prevent iron deficiency. In the present study, we explored the effect of three consecutive days of endurance training (twice daily) on the hepcidin-25 (hepcidin) level. The effect of iron supplementation during this period was also determined. Fourteen male endurance athletes were enrolled and randomly assigned to either an iron-treated condition (Fe condition, n = 7) or a placebo condition (Control condition; CON, n = 7). They engaged in two 75-min sessions of treadmill running at 75% of maximal oxygen uptake on three consecutive days (days 1-3). The Fe condition took 12 mg of iron twice daily (24 mg/day), and the CON condition did not. On day 1, both conditions exhibited significant increases in serum hepcidin and plasma interleukin-6 levels after exercise ( p < 0.05). In the CON condition, the hepcidin level did not change significantly throughout the training period. However, in the Fe condition, the serum hepcidin level on day 4 was significantly higher than that of the CON condition ( p < 0.05). In conclusion, the hepcidin level was significantly elevated following three consecutive days of endurance training when moderate doses of iron were taken.

Integrated Care Planning for Cancer Patients: A Scoping Review

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Anum Irfan Khan

2017-11-01

Full Text Available Introduction: There has been a growing emphasis on the use of integrated care plans to deliver cancer care. However little is known about how integrated care plans for cancer patients are developed including featured core activities, facilitators for uptake and indicators for assessing impact. Methods: Given limited consensus around what constitutes an integrated care plan for cancer patients, a scoping review was conducted to explore the components of integrated care plans and contextual factors that influence design and uptake. Results: Five types of integrated care plans based on the stage of cancer care: surgical, systemic, survivorship, palliative and comprehensive (involving a transition between stages are described in current literature. Breast, esophageal and colorectal cancers were common disease sites. Multi-disciplinary teams, patient needs assessment and transitional planning emerged as key features. Provider buy-in and training alongside informational technology support served as important facilitators for plan uptake. Provider-level measurement was considerably less robust compared to patient and system-level indicators. Conclusions: Similarities in design features, components and facilitators across the various types of integrated care plans indicates opportunities to leverage shared features and enable a management lens that spans the trajectory of a patient’s journey rather than a phase-specific silo approach to care.

Facilitation of trace metal uptake in cells by inulin coating of metallic nanoparticles

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Santillán-Urquiza, Esmeralda; Arteaga-Cardona, Fernando; Torres-Duarte, Cristina; Cole, Bryan; Wu, Bing; Méndez-Rojas, Miguel A.; Cherr, Gary N.

2017-09-01

Trace elements such as zinc and iron are essential for the proper function of biochemical processes, and their uptake and bioavailability are dependent on their chemical form. Supplementation of trace metals through nanostructured materials is a new field, but its application raises concerns regarding their toxicity. Here, we compared the intracellular zinc uptake of different sources of zinc: zinc sulfate, and ZnO and core-shell α-Fe2O3@ZnO nanoparticles, coated or uncoated with inulin, an edible and biocompatible polysaccharide. Using mussel haemocytes, a well-known model system to assess nanomaterial toxicity, we simultaneously assessed zinc accumulation and multiple cellular response endpoints. We found that intracellular zinc uptake was strongly enhanced by inulin coating, in comparison to the uncoated nanoparticles, while no significant effects on cell death, cell viability, mitochondrial membrane integrity, production of reactive oxygen species or lysosome abundance were observed at concentrations up to 20 ppm. Since no significant increments in toxicity were observed, the coated nanomaterials may be useful to increase in vivo zinc uptake for nutritional applications.

Iron oxide nanoparticles surface coating and cell uptake affect biocompatibility and inflammatory responses of endothelial cells and macrophages

Energy Technology Data Exchange (ETDEWEB)

Orlando, Antonina [University of Milano-Bicocca, Department of Health Sciences (Italy); Colombo, Miriam; Prosperi, Davide [University of Milano-Bicocca, Department of Biotechnology and Biosciences (Italy); Gregori, Maria; Panariti, Alice; Rivolta, Ilaria; Masserini, Massimo; Cazzaniga, Emanuela, E-mail: emanuela.cazzaniga@unimib.it [University of Milano-Bicocca, Department of Health Sciences (Italy)

2015-09-15

Engineered iron oxide nanoparticles (IONP) offer the possibility of a wide range of medical uses, from clinical imaging to magnetically based hyperthermia for tumor treatment. These applications require their systemic administration in vivo. An important property of nanoparticles is their stability in biological media. For this purpose, a multicomponent nanoconstruct combining high colloidal stability and improved physical properties was synthesized and characterized. IONP were coated with an amphiphilic polymer (PMA), which confers colloidal stability, and were pegylated in order to obtain the nanoconstruct PEG-IONP-PMA. The aim of this study was to utilize cultured human endothelial cells (HUVEC) and murine macrophages, taken as model of cells exposed to NP after systemic administration, to assess the biocompatibility of PEG-IONP-PMA (23.1 ± 1.4 nm) or IONP-PMA (15.6 ± 3.4 nm). PEG-IONP-PMA, tested at different concentrations as high as 20 μg mL{sup −1}, exhibited no cytotoxicity or inflammatory responses. By contrast, IONP-PMA showed a concentration-dependent increase of cytotoxicity and of TNF-α production by macrophages and NO production by HUVECs. Cell uptake analysis suggested that after PEGylation, IONP were less internalized either by macrophages or by HUVEC. These results suggest that the choice of the polymer and the chemistry of surface functionalization are a crucial feature to confer to IONP biocompatibility.

Iron and stony-iron meteorites

DEFF Research Database (Denmark)

Ruzicka, Alex M.; Haack, Henning; Chabot, Nancy L.

2017-01-01

By far most of the melted and differentiated planetesimals that have been sampled as meteorites are metal-rich iron meteorites or stony iron meteorites. The parent asteroids of these meteorites accreted early and differentiated shortly after the solar system formed, producing some of the oldest...... and interpretations for iron and stony iron meteorites (Plate 13.1). Such meteorites provide important constraints on the nature of metal-silicate separation and mixing in planetesimals undergoing partial to complete differentiation. They include iron meteorites that formed by the solidification of cores...... (fractionally crystallized irons), irons in which partly molten metal and silicates of diverse types were mixed together (silicate-bearing irons), stony irons in which partly molten metal and olivine from cores and mantles were mixed together (pallasites), and stony irons in which partly molten metal...

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

International Nuclear Information System (INIS)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-01-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

Energy Technology Data Exchange (ETDEWEB)

Katebi, Samira; Esmaeili, Abolghasem, E-mail: aesmaeili@sci.ui.ac.ir; Ghaedi, Kamran

2016-03-15

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

Effect of Biofertilizers on Macro and Micro Nutrients Uptake and Essential Oil Content in Dracocephalum moldavica L.

Directory of Open Access Journals (Sweden)

S Rahimzadeh

2013-08-01

Full Text Available In order to investigation the effect of different fertilization treatments on nutrient and essential oil contents in dragonhead drug (Dracocephalum moldavica L., an experiment was conducted in the station of agricultural research in Urmia on 2008. Treatments (nitroxin, barvar phosphate biofertilizer, biosulfur, nitroxin+ barvar phosphate biofertilizer, barvar phosphate biofertilizer + biosulfur, nitroxin+ biosulfur, nitroxin+ barvar phosphate biofertilizer + biosulfur, chemical fertilizer, control were arranged based on randomized complete block design with 4 replications. Results indicated that uptake of Nitrogen, Phosphorus, Potassium, Iron, Copper, Manganese and essential oil content were affected by studied treatments significantly but uptake of zinc by plant was not affected. Means comparison showed the highest values of Nitrogen (3.55%, Potassium (3.47% and Iron (4.56 ppm in Nitroxin treatment, Phosphorus (0.26% and Copper (0.33 ppm in barvar phosphate biofertilizer + biosulfur treatment, Manganese (0.48 ppm in chemical origin of nitrogen+phosphorus+ potassium treatment and essential oil content (0.48% in nitroxin+ barvar phosphate biofertilizer + biosulfur treatment

Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

DEFF Research Database (Denmark)

Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem

2014-01-01

The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

Kinetics of Transferrin and Transferrin-Receptor during Iron Transport through Blood Brain Barrier

Science.gov (United States)

Khan, Aminul; Liu, Jin; Dutta, Prashanta

2017-11-01

Transferrin and its receptors play an important role during the uptake and transcytosis of iron by blood brain barrier (BBB) endothelial cells to maintain iron homeostasis in BBB endothelium and brain. In the blood side of BBB, ferric iron binds with the apo-transferrin to form holo-transferrin which enters the endothelial cell via transferrin receptor mediated endocytosis. Depending on the initial concentration of iron inside the cell endocytosed holo-transferrin can either be acidified in the endosome or exocytosed through the basolateral membrane. Acidification of holo-transferrin in the endosome releases ferrous irons which may either be stored and used by the cell or transported into brain side. Exocytosis of the holo-transferrin through basolateral membrane leads to transport of iron bound to transferrin into brain side. In this work, kinetics of internalization, recycling and exocytosis of transferrin and its receptors are modeled by laws of mass action during iron transport in BBB endothelial cell. Kinetic parameters for the model are determined by least square analysis. Our results suggest that the cell's initial iron content determines the extent of the two possible iron transport pathways, which will be presented in this talk Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

Evaluation of renal uptake on 111InCl3 bone marrow scintigraphy in patients with aplastic anemia and myelodysplastic syndrome

International Nuclear Information System (INIS)

Koizumi, Mitsuru; Goto, Masafumi; Nomura, Toshiharu; Watari, Tsutomu; Saito, Kenji

1993-01-01

High renal uptake on bone marrow scan with indium-111 chloride is often shown in patients with bone marrow abnormality. We evaluated the renal uptake on bone marrow scan in 27 cases of aplastic anemia, 20 cases of myelodysplastic syndrome (MDS) and 10 cases of other diseases. The high renal uptake was observed in patients not only with aplastic anemia but also with MDS. The renal uptake correlated with blood transfusion units, unsaturated iron binding capacity (UIBC), blood pool imaging and bone marrow uptake. The renal uptake correlated with UIBC better than with the blood transfusion units. Following mechanism of the renal uptake is proposed that frequent blood transfusion makes low UIBC, and the low UIBC causes the failure to chelate indium with transferrin. The fast blood clearance of un-chelated indium via kidneys is followed. Hypoplastic bone marrow may also play an important role for the high renal uptake because all patients with the high renal uptake could not be explained by above mentioned mechanism. Caution should be paid to the scans with the high renal uptake because both aplastic anemia and MDS patients show the high renal uptake. (author)

Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening

NARCIS (Netherlands)

van Schendel, Rachèl V.; Kleinveld, Johanna H.; Dondorp, Wybo J.; Pajkrt, Eva; Timmermans, Danielle R. M.; Holtkamp, Kim C. A.; Karsten, Margreet; Vlietstra, Anne L.; Lachmeijer, Augusta M. A.; Henneman, Lidewij

2014-01-01

Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The

Size-Dependent Accumulation of PEGylated Silane-Coated Magnetic Iron Oxide Nanoparticles in Murine Tumors

DEFF Research Database (Denmark)

Larsen, Esben Kjær Unmack; Nielsen, T.; Wittenborn, T.

2009-01-01

following intravenous injection. Biocompatible iron oxide MNPs coated with PEG were prepared by replacing oleic acid with a biocompatible and commercially available silane-PEG to provide an easy and effective method for chemical coating. The colloidal stable PEGylated MNPs were magnetically separated...... into two distinct size subpopulations of 20 and 40 nm mean diameters with increased phagocytic uptake observed for the 40 nm size range in vitro. MRI detection revealed greater iron accumulation in murine tumors for 40 nm nanoparticles after intravenous injection. The enhanced MRI contrast of the larger...

Maternal Iron Nutriture as a Critical Modulator of FASD Risk in Alcohol-Exposed Pregnancies

Science.gov (United States)

Helfrich, Kaylee K.; Saini, Nipun; Kling, Pamela J.; Smith, Susan M.

2018-01-01

Alcohol consumption during pregnancy places the fetus at risk for permanent physical, cognitive, and behavioral impairments, collectively termed fetal alcohol spectrum disorders (FASD). However, prenatal alcohol exposure (PAE) outcomes vary widely, and growing evidence suggests that maternal nutrition is a modifying factor. Certain nutrients, such as iron, may modulate FASD outcomes. Untreated gestational iron deficiency (ID) causes persistent neurodevelopmental deficits in the offspring that affect many of the same domains damaged by PAE. Although chronic alcohol consumption enhances iron uptake and elevates liver iron stores in adult alcoholics, alcohol-abusing premenopausal women often have low iron reserves due to menstruation, childbirth, and poor diet. Recent investigations show that low iron reserves in during pregnancy are strongly associated with a worsening of several hallmark features in FASD including reduced growth and impaired associative learning. This review discusses recent clinical and animal model findings that maternal ID worsens fetal outcomes in response to PAE. It also discusses underlying mechanisms by which PAE disrupts maternal and fetal iron homeostasis. We suggest that alcohol-exposed, ID pregnancies contribute to the severe end of the FASD spectrum. PMID:29017023

Multi-domain CGFS-type glutaredoxin Grx4 regulates iron homeostasis via direct interaction with a repressor Fep1 in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyoung-Dong; Kim, Hyo-Jin; Lee, Kyung-Chang [Laboratory of Molecular Microbiology, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742 (Korea, Republic of); Roe, Jung-Hye, E-mail: jhroe@snu.ac.kr [Laboratory of Molecular Microbiology, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742 (Korea, Republic of)

2011-05-20

Research highlights: {yields} Monothiol glutaredoxin Grx4 allows Fep1-mediated de-repression of iron uptake genes at low iron. {yields} Grx4 directly interacts with Fep1 in vivo and in vitro. {yields} The Cys172 in the CGFS motif of Grx4 is necessary for cell proliferation and iron regulation. {yields} The Cys172 of Grx4 is required for normal interaction with Fep1. -- Abstract: The fission yeast Schizosaccharomyces pombe contains two CGFS-type monothiol glutaredoxins, Grx4 and Grx5, which are localized primarily in the nucleus and mitochondria, respectively. We observed involvement of Grx4 in regulating iron-responsive gene expression, which is modulated by a repressor Fep1. Lack of Grx4 caused defects not only in growth but also in the expression of both iron-uptake and iron-utilizing genes regardless of iron availability. In order to unravel how Grx4 is involved in Fep1-mediated regulation, interaction between them was investigated. Co-immunoprecipitation and bimolecular fluorescence complementation (BiFC) revealed that Grx4 physically interacts with Fep1 in vivo. BiFC revealed localized nuclear dots produced by interaction of Grx4 with Fep1. Mutation of cysteine-172 in the CGFS motif to serine (C172S) produced effects similarly observed under Grx4 depletion, such as the loss of iron-dependent gene regulation and the absence of nuclear dots in BiFC analysis. These results suggest that the ability of Grx4 to bind iron, most likely Fe-S cofactor, could be critical in interacting with and modulating the activity of Fep1.

Preferential magnetic nanoparticle uptake by bone marrow derived macrophages sub-populations: effect of surface coating on polarization, toxicity, and in vivo MRI detection

Energy Technology Data Exchange (ETDEWEB)

Al Faraj, Achraf, E-mail: aalfaraj@ksu.edu.sa [College of Applied Medical Sciences, King Saud University, Molecular and Cellular Imaging Lab, Department of Radiological Sciences (Saudi Arabia)

2013-07-15

Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of different diseases, which make them attractive vehicles to deliver contrast agents or drugs for diagnostic or therapeutic purposes. In this study, the effect of polyethylene glycol functionalization of magnetic iron oxide nanoparticles and their further surface modification with carboxylic groups on bone marrow-derived M1 and M2 macrophages phenotype, labeling efficiency, uptake mechanism, biocompatibility, and their in vivo MR detection was assessed. An enhanced labeling efficiency was observed for carboxylic surface-modified superparamagnetic iron oxide (SPIO) compared to PEGylated SPIO and to a higher extent to plain SPIO along with a higher uptake by M2 subsets. Magnetic nanoparticles were found located in the periphery of the vesicles dispersed in the cytoplasm in TEM. Investigation of the labeling mechanism by inhibiting different uptake pathways revealed that endocytosis via scavenger receptor A, a process known to be clathrin mediated, plays a central role in the cellular uptake kinetics of both macrophages subpopulations. Biocompatibility evaluation showed no variation in cell viability and mitochondrial membrane potential with a low release of ROS. Flow cytometry and measurement of iNOS and Arginase 1 activity as marker of M1 and M2 macrophages polarization confirmed that magnetic labeling of macrophages subsets did not affect their polarization. In addition, no variation was observed in the biodistribution of magnetic iron oxide-labeled M1 and M2 macrophages subsets when monitored using noninvasive magnetic resonance imaging with a better detection for the enhanced SPIO-PEG-COOH-labeled cells.

Preferential magnetic nanoparticle uptake by bone marrow derived macrophages sub-populations: effect of surface coating on polarization, toxicity, and in vivo MRI detection

International Nuclear Information System (INIS)

Al Faraj, Achraf

2013-01-01

Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of different diseases, which make them attractive vehicles to deliver contrast agents or drugs for diagnostic or therapeutic purposes. In this study, the effect of polyethylene glycol functionalization of magnetic iron oxide nanoparticles and their further surface modification with carboxylic groups on bone marrow-derived M1 and M2 macrophages phenotype, labeling efficiency, uptake mechanism, biocompatibility, and their in vivo MR detection was assessed. An enhanced labeling efficiency was observed for carboxylic surface-modified superparamagnetic iron oxide (SPIO) compared to PEGylated SPIO and to a higher extent to plain SPIO along with a higher uptake by M2 subsets. Magnetic nanoparticles were found located in the periphery of the vesicles dispersed in the cytoplasm in TEM. Investigation of the labeling mechanism by inhibiting different uptake pathways revealed that endocytosis via scavenger receptor A, a process known to be clathrin mediated, plays a central role in the cellular uptake kinetics of both macrophages subpopulations. Biocompatibility evaluation showed no variation in cell viability and mitochondrial membrane potential with a low release of ROS. Flow cytometry and measurement of iNOS and Arginase 1 activity as marker of M1 and M2 macrophages polarization confirmed that magnetic labeling of macrophages subsets did not affect their polarization. In addition, no variation was observed in the biodistribution of magnetic iron oxide-labeled M1 and M2 macrophages subsets when monitored using noninvasive magnetic resonance imaging with a better detection for the enhanced SPIO–PEG–COOH-labeled cells

Paving a Path to Understanding Metabolic Responses to Iron Bioavailability: Global Proteomic Analysis of Crocosphaera watsonii

Science.gov (United States)

Gauglitz, J.; McIlvin, M. R.; Moran, D. M.; Waterbury, J. B.; Saito, M. A.

2016-02-01

Marine diazotrophic cyanobacteria provide a key source of new nitrogen into the oceans and are important contributors to primary production. The geographic distribution of these cyanobacteria is impacted by available iron and phosphorus as well as environmental conditions such as temperature, however available iron concentrations are thought to be particularly critical due to the high demand for iron in cellular processes. Iron bioavailability and microorganismal adaptations to low iron environments may thus play a key role in dictating community structure, however the mechanisms by which cyanobacteria acquire iron and regulate its uptake are not well defined. In this study, the unicellular diazotroph, Crocosphaera watsonii WH8501, was acclimated to a range of bioavailable iron concentrations (from 0.001nM to 8.13nM Fe') using trace metal clean culturing techniques and the proteomes were analyzed by LC/MS-MS. Physiological and proteomic data indicate three distinct phenotypic ranges: iron-replete, iron-limited, and iron-starved. Trends in photosynthetic, carbon fixation and iron storage proteins across the iron gradient indicate that the C. watsonii proteome responds directly to iron availability. Further analysis of relative protein expression, which describes the physiological state of the cell, will lead to insights into how C. watsonii is able to adapt to iron-limited conditions and the resulting biogeochemical implications will be discussed.

Overexpression of Arabidopsis VIT1 increases accumulation of iron in cassava roots and stems.

Science.gov (United States)

Narayanan, Narayanan; Beyene, Getu; Chauhan, Raj Deepika; Gaitán-Solis, Eliana; Grusak, Michael A; Taylor, Nigel; Anderson, Paul

2015-11-01

Iron is extremely abundant in the soil, but its uptake in plants is limited due to low solubility in neutral or alkaline soils. Plants can rely on rhizosphere acidification to increase iron solubility. AtVIT1 was previously found to be involved in mediating vacuolar sequestration of iron, which indicates a potential application for iron biofortification in crop plants. Here, we have overexpressed AtVIT1 in the starchy root crop cassava using a patatin promoter. Under greenhouse conditions, iron levels in mature cassava storage roots showed 3-4 times higher values when compared with wild-type plants. Significantly, the expression of AtVIT1 showed a positive correlation with the increase in iron concentration of storage roots. Conversely, young leaves of AtVIT1 transgenic plants exhibit characteristics of iron deficiency such as interveinal chlorosis of leaves (yellowing) and lower iron concentration when compared with the wild type plants. Interestingly, the AtVIT1 transgenic plants showed 4 and 16 times higher values of iron concentration in the young stem and stem base tissues, respectively. AtVIT1 transgenic plants also showed 2-4 times higher values of iron content when compared with wild-type plants, with altered partitioning of iron between source and sink tissues. These results demonstrate vacuolar iron sequestration as a viable transgenic strategy to biofortify crops and to help eliminate micronutrient malnutrition in at-risk human populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Iron deficiency regulated OsOPT7 is essential for iron homeostasis in rice.

Science.gov (United States)

Bashir, Khurram; Ishimaru, Yasuhiro; Itai, Reiko Nakanishi; Senoura, Takeshi; Takahashi, Michiko; An, Gynheung; Oikawa, Takaya; Ueda, Minoru; Sato, Aiko; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K

2015-05-01

The molecular mechanism of iron (Fe) uptake and transport in plants are well-characterized; however, many components of Fe homeostasis remain unclear. We cloned iron-deficiency-regulated oligopeptide transporter 7 (OsOPT7) from rice. OsOPT7 localized to the plasma membrane and did not transport Fe(III)-DMA or Fe(II)-NA and GSH in Xenopus laevis oocytes. Furthermore OsOPT7 did not complement the growth of yeast fet3fet4 mutant. OsOPT7 was specifically upregulated in response to Fe-deficiency. Promoter GUS analysis revealed that OsOPT7 expresses in root tips, root vascular tissue and shoots as well as during seed development. Microarray analysis of OsOPT7 knockout 1 (opt7-1) revealed the upregulation of Fe-deficiency-responsive genes in plants grown under Fe-sufficient conditions, despite the high Fe and ferritin concentrations in shoot tissue indicating that Fe may not be available for physiological functions. Plants overexpressing OsOPT7 do not exhibit any phenotype and do not accumulate more Fe compared to wild type plants. These results indicate that OsOPT7 may be involved in Fe transport in rice.

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency.

Science.gov (United States)

Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-11-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Chemical composition and effects of micronized corn bran on iron bioavailability in rats

Directory of Open Access Journals (Sweden)

Gilson Irineu de Oliveira Junior

2014-09-01

Full Text Available The degermination of corn grains by dry milling generates 5% of a fibrous residue. After segregation and micronization, corn bran becomes a potential source of dietary fiber consumption. However, its effect on iron bioavailability has not been reported in the literature. The objective of the present study was to determine the nutritional composition of corn bran and its effects on iron bioavailability using the hemoglobin depletion-repletion method in rats. The animals were divided into two groups: cellulose (control and corn bran (experimental. The bran had high content of total dietary fiber, especially the insoluble fraction, and low phytate content. Hemoglobin uptake did not differ between groups at the end of repletion period, and the iron relative bioavailability value of the corn bran diet was 104% in comparison to that of the control group. The product evaluated proved to be a potential source of dietary fiber and it showed no negative effects on iron bioavailability.

Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology.

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Chung-Yi Yang

Full Text Available Superparamagnetic iron oxide (SPIO nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45-60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R(2 = 0. 8048. For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.

Photoreductive dissolution of iron oxides trapped in ice and its environmental implications.

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Kim, Kitae; Choi, Wonyong; Hoffmann, Michael R; Yoon, Ho-Il; Park, Byong-Kwon

2010-06-01

The availability of iron has been thought to be a main limiting factor for the productivity of phytoplankton and related with the uptake of atmospheric CO(2) and algal blooms in fresh and sea waters. In this work, the formation of bioavailable iron (Fe(II)(aq)) from the dissolution of iron oxide particles was investigated in the ice phase under both UV and visible light irradiation. The photoreductive dissolution of iron oxides proceeded slowly in aqueous solution (pH 3.5) but was significantly accelerated in polycrystalline ice, subsequently releasing more bioavailable ferrous iron upon thawing. The enhanced photogeneration of Fe(II)(aq) in ice was confirmed regardless of the type of iron oxides [hematite, maghemite (gamma-Fe(2)O(3)), goethite (alpha-FeOOH)] and the kind of electron donors. The ice-enhanced dissolution of iron oxides was also observed under visible light irradiation, although the dissolution rate was much slower compared with the case of UV radiation. The iron oxide particles and organic electron donors (if any) in ice are concentrated and aggregated in the liquid-like grain boundary region (freeze concentration effect) where protons are also highly concentrated (lower pH). The enhanced photodissolution of iron oxides should occur in this confined boundary region. We hypothesized that electron hopping through the interconnected grain boundaries of iron oxide particles facilitates the separation of photoinduced charge pairs. The outdoor experiments carried out under ambient solar radiation of Ny-Alesund (Svalbard, 78 degrees 55'N) also showed that the generation of dissolved Fe(II)(aq) via photoreductive dissolution is enhanced when iron oxides are trapped in ice. Our results imply that the ice(snow)-covered surfaces and ice-cloud particles containing iron-rich mineral dusts in the polar and cold environments provide a source of bioavailable iron when they thaw.

Control of Fur synthesis by the non-coding RNA RyhB and iron-responsive decoding.

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Vecerek, Branislav; Moll, Isabella; Bläsi, Udo

2007-02-21

The Fe2+-dependent Fur protein serves as a negative regulator of iron uptake in bacteria. As only metallo-Fur acts as an autogeneous repressor, Fe2+scarcity would direct fur expression when continued supply is not obviously required. We show that in Escherichia coli post-transcriptional regulatory mechanisms ensure that Fur synthesis remains steady in iron limitation. Our studies revealed that fur translation is coupled to that of an upstream open reading frame (uof), translation of which is downregulated by the non-coding RNA (ncRNA) RyhB. As RyhB transcription is negatively controlled by metallo-Fur, iron depletion creates a negative feedback loop. RyhB-mediated regulation of uof-fur provides the first example for indirect translational regulation by a trans-encoded ncRNA. In addition, we present evidence for an iron-responsive decoding mechanism of the uof-fur entity. It could serve as a backup mechanism of the RyhB circuitry, and represents the first link between iron availability and synthesis of an iron-containing protein.

Capture and storage of hydrogen gas by zero-valent iron.

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Reardon, Eric J

2014-02-01

Granular Fe(o), used to reductively degrade a variety of contaminants in groundwater, corrodes in water to produce H2(g). A portion enters the Fe(o) lattice where it is stored in trapping sites such as lattice defects and microcracks. The balance is dissolved by the groundwater where it may exsolve as a gas if its solubility is exceeded. Gas exsolution can reduce the effectiveness of the Fe(o) treatment zone by reducing contact of the contaminant with iron surfaces or by diverting groundwater flow. It also represents a lost electron resource that otherwise could be involved in reductive degradation of contaminants. It is advantageous to select an iron for remediation purposes that captures a large proportion of the H2(g) it generates. This study examines various aspects of the H2(g) uptake process and has found 1) H2(g) does not have to be generated at the water/iron interface to enter the lattice. It can enter directly from the gas/water phases, 2) exposure of granular sponge iron to H2(g) reduces the dormant period for the onset of iron corrosion, 3) the large quantities of H2(g) generated by nano-Fe(o) injected into a reactive barrier of an appropriate granular iron can be captured in the lattice of that iron, and 4) lattice-bound hydrogen represents an additional electron resource to Fe(o) for remediation purposes and may be accessible using physical or chemical means. Copyright © 2013 Elsevier B.V. All rights reserved.

A proteome analysis of the response of a Pseudomonas aeruginosa oxyR mutant to iron limitation.

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Vinckx, Tiffany; Wei, Qing; Matthijs, Sandra; Noben, Jean-Paul; Daniels, Ruth; Cornelis, Pierre

2011-06-01

In Pseudomonas aeruginosa the response to oxidative stress is orchestrated by the LysR regulator OxyR by activation of the transcription of two catalase genes (katA and katB), of the alkyl-hydroxyperoxidases ahpCF and ahpB. Next to the expected high sensitivity to oxidative stress generated by reactive oxygen species (ROS: H(2)O(2), O(2)(-)), the oxyR mutant shows a defective growth under conditions of iron limitation (Vinckx et al. 2008). Although production and uptake of the siderophore pyoverdine is not affected by the absence of oxyR, the mutant is unable to satisfy its need for iron when grown under iron limiting conditions. In order to get a better insight into the effects caused by iron limitation on the physiological response of the oxyR mutant we decided to compare the proteomes of the wild type and the mutant grown in the iron-poor casamino acids medium (CAA), in CAA plus H(2)O(2), and in CAA plus the strong iron chelator ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) (EDDHA). Especially in the presence of hydrogen peroxide the oxyR cells increase the production of stress proteins (Dps and IbpA). The superoxide dismutase SodM is produced in higher amounts in the oxyR mutant grown in CAA plus H(2)O(2). The PchB protein, a isochorismate-pyruvate lyase involved in the siderophore pyochelin biosynthesis is not detectable in the extracts from the oxyR mutant grown in the presence of hydrogen peroxide. When cells were grown in the presence of EDDHA, we observed a reduction of the ferric uptake regulator (Fur), and an increase in the two subunits of the succinyl-CoA synthetase and the fumarase FumC1.

Transcriptome Analysis of the Intracellular Facultative Pathogen Piscirickettsia salmonis: Expression of Putative Groups of Genes Associated with Virulence and Iron Metabolism.

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Alvaro Machuca

Full Text Available The intracellular facultative bacteria Piscirickettsia salmonis is one of the most important pathogens of the Chilean aquaculture. However, there is a lack of information regarding the whole genomic transcriptional response according to different extracellular environments. We used next generation sequencing (NGS of RNA (RNA-seq to study the whole transcriptome of an isolate of P. salmonis (FAVET-INBIOGEN using a cell line culture and a modified cell-free liquid medium, with or without iron supplementation. This was done in order to obtain information about the factors there are involved in virulence and iron acquisition. First, the isolate was grown in the Sf21 cell line; then, the bacteria were cultured into a cell-free liquid medium supplemented or not with iron. We identified in the transcriptome, genes associated with type IV secretion systems, genes related to flagellar structure assembly, several proteases and sigma factors, and genes related to the development of drug resistance. Additionally, we identified for the first time several iron-metabolism associated genes including at least two iron uptake pathways (ferrous iron and ferric iron uptake that are actually expressed in the different conditions analyzed. We further describe putative genes that are related with the use and storage of iron in the bacteria, which have not been previously described. Several sets of genes related to virulence were expressed in both the cell line and cell-free culture media (for example those related to flagellar structure; such as basal body, MS-ring, C-ring, proximal and distal rod, and filament, which may play roles in other basic processes rather than been restricted to virulence.

New Insights on Iron Study in Myelodysplasia

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Noha M. El Husseiny

2014-12-01

Full Text Available OBJECTIVE: Hepcidin plays a pivotal role in iron homeostasis. It is predominantly produced by hepatocytes and inhibits iron release from macrophages and iron uptake by intestinal epithelial cells. Competitive ELISA is the current method of choice for the quantification of serum hepcidin because of its lower detection limit, low costs, and high throughput. This study aims to discuss the role of hepcidin in the pathogenesis of iron overload in recently diagnosed myelodysplasia (MDS cases. METHODS: The study included 21 recently diagnosed MDS patients and 13 healthy controls. Ferritin, hepcidin, and soluble transferrin receptor (sTFR were measured in all subjects. RESULTS: There were 7 cases of hypocellular MDS, 8 cases of refractory cytopenia with multilineage dysplasia, and 6 cases of refractory anemia with excess blasts. No difference was observed among the 3 MDS subtypes in terms of hepcidin, sTFR, and ferritin levels (p>0.05. Mean hepcidin levels in the MDS and control groups were 55.8±21.5 ng/mL and 19.9±2.6 ng/ mL, respectively. Mean sTFR was 45.7±8.8 nmol/L in MDS patients and 31.1±5.6 nmol/L in the controls. Mean ferritin levels were significantly higher in MDS patients than in controls (539.14±83.5 ng/mL vs. 104.6±42.9 ng/mL, p0.05. CONCLUSION: Hepcidin may not be the main cause of iron overload in MDS. Further studies are required to test failure of production or peripheral unresponsiveness to hepcidin in MDS cases.

Uptake, distribution, and incorporation of 59Fe in tissue and blood of rainbow trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Walker, R.L.

1975-01-01

A study was designed to evaluate the storage iron facilities in various tissues and to trace the distribution of radioiron in tissues and blood following an intraperitoneal (i.p.) injection of 59 Fe. Iron deficiency anemia was induced in an experimental group of rainbow trout in order to measure its effect on red blood cell production and mobilization of storage iron. Most of the 59 Fe was absorbed from the peritoneal cavity within 24 hrs. after the i.p. injection. Equilibrium between the plasma 59 Fe pool and that of the tissue was established by day 8. Experimental fish RBC 59 Fe content increased to 70 to 80 percent of the initial injected dose by day 16 compared to 50 percent in the controls. This was attributed to the difference in reticulocyte count which was 10 to 12 percent for the bled and 2 to 3 percent for control fish. The rate that iron is incorporated into hemoglobin by immature red cells is much slower (about half) than the rate of RBC 59 Fe uptake, thus, iron is temporarily stored in the cytoplasm. The iron for hemoglobin formation was obtained from liver iron stores which dropped from 12 percent to less than 1 percent of the initial injected dose by day 16. Total iron concentration in liver decreased from 200 to less than 100 μg Fe/g. The decrease in liver iron may have stimulated iron absorption by the intestine and pyloric caeca. There is evidence for a feedback mechanism mediated by transferrin

Iron and stony-iron meteorites

DEFF Research Database (Denmark)

Benedix, Gretchen K.; Haack, Henning; McCoy, T. J.

2014-01-01

Without iron and stony-iron meteorites, our chances of ever sampling the deep interior of a differentiated planetary object would be next to nil. Although we live on a planet with a very substantial core, we will never be able to sample it. Fortunately, asteroid collisions provide us with a rich...... sampling of the deep interiors of differentiated asteroids. Iron and stony-iron meteorites are fragments of a large number of asteroids that underwent significant geological processing in the early solar system. Parent bodies of iron and some stony-iron meteorites completed a geological evolution similar...... to that continuing on Earth – although on much smaller length- and timescales – with melting of the metal and silicates; differentiation into core, mantle, and crust; and probably extensive volcanism. Iron and stony-iron meteorites are our only available analogues to materials found in the deep interiors of Earth...

Evaluation of renal uptake on [sup 111]InCl[sub 3] bone marrow scintigraphy in patients with aplastic anemia and myelodysplastic syndrome

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Koizumi, Mitsuru; Goto, Masafumi; Nomura, Toshiharu; Watari, Tsutomu; Saito, Kenji (Dokkyo Univ. School of Medicine, Mibu, Tochigi (Japan))

1993-04-01

High renal uptake on bone marrow scan with indium-111 chloride is often shown in patients with bone marrow abnormality. We evaluated the renal uptake on bone marrow scan in 27 cases of aplastic anemia, 20 cases of myelodysplastic syndrome (MDS) and 10 cases of other diseases. The high renal uptake was observed in patients not only with aplastic anemia but also with MDS. The renal uptake correlated with blood transfusion units, unsaturated iron binding capacity (UIBC), blood pool imaging and bone marrow uptake. The renal uptake correlated with UIBC better than with the blood transfusion units. Following mechanism of the renal uptake is proposed that frequent blood transfusion makes low UIBC, and the low UIBC causes the failure to chelate indium with transferrin. The fast blood clearance of un-chelated indium via kidneys is followed. Hypoplastic bone marrow may also play an important role for the high renal uptake because all patients with the high renal uptake could not be explained by above mentioned mechanism. Caution should be paid to the scans with the high renal uptake because both aplastic anemia and MDS patients show the high renal uptake. (author).

Recognition and uptake of free and nanoparticle‐bound betalactoglobulin – a food allergen – by human monocytes

DEFF Research Database (Denmark)

Marengo, Mauro; Bonomi, Francesco; Iametti, Stefania

2011-01-01

Scope: To improve our understanding of the interaction of food allergens with cells of the immune system, the endocytosis by human monocytes of bovine β‐lactoglobulin (BLG) and ovomucoid (OM) – two major food allergens – and human serum albumin (HSA) was studied. Methods and results: BLG......, and HSA were conjugated to MNPs also labeled with a fluorescent probe. The uptake of these materials by human monocytes was monitored through flow cytometry, and compared with fluorescent MNPs and the free fluorescently labeled proteins, confirming higher uptake of the BLG‐conjugated MNPs versus non......‐conjugated MNPs. OM but not HSA conjugation to particles enhanced uptake of the MNPs. Confocal microscopy provided direct evidence of the actual internalization of BLG–MNP conjugates into the cytoplasm. Conclusions: These results contribute to the current understanding of the interaction between food allergens...

Effect of an industrial chemical waste on the uptake of cations by green oat

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HORTENSIA RADULESCU

2007-06-01

Full Text Available Calcium carbonate, obtained as a waste in the industrial manufacture of magnesium carbonate and magnesium oxide from dolomites, can be applied in agriculture. The appreciable amounts of calcium and magnesium in this waste, together with impurities such as iron, zinc, manganese, chromium and copper compounds can be useful in soil amendment and plant nutrition. This paper presents preliminary results of the testing of several waste doses on soil, pursuing their effect on the uptake of cations by green oat (Avena sativa L.. The obtained results show an increase in the amount of calcium, magnesium, zinc and copper found in green oat plants, as well as a decrease of the content of iron and manganese with increasing waste dose. These results may be explained by lower absorptions of iron andmanganese because of the antagonistic effect created by high amounts of calcium and magnesium, as well as by the presence of copper and zinc.

Obligatory reduction of ferric chelates in iron uptake by soybeans.

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Chaney, R L; Brown, J C; Tiffin, L O

1972-08-01

The contrasting Fe(2+) and Fe(3+) chelating properties of the synthetic chelators ethylenediaminedi (o-hydroxyphenylacetate) (EDDHA) and 4,7-di(4-phenylsulfonate)-1, 10-phenanthroline (bathophenanthrolinedisulfonate) (BPDS) were used to determine the valence form of Fe absorbed by soybean roots supplied with Fe(3+)-chelates. EDDHA binds Fe(3+) strongly, but Fe(2+) weakly; BPDS binds Fe(2+) strongly but Fe(3+) weakly. Addition of an excess of BPDS to nutrient solutions containing Fe(3+)-chelates inhibited soybean Fe uptake-translocation by 99+%; [Fe(II) (BPDS)(3)](4-) accumulated in the nutrient solution. The addition of EDDHA caused little or no inhibition. These results were observed with topped and intact soybeans. Thus, separation and absorption of Fe from Fe(3+)-chelates appear to require reduction of Fe(3+)-chelate to Fe(2+)-chelate at the root, with Fe(2+) being the principal form of Fe absorbed by soybean.

Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

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Nils Bohmer

2015-01-01

Full Text Available Nanomedicine is a rapidly growing field in nanotechnology, which has great potential in the development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer as a model cell line. Cells were transfected with specific siRNAs against Caveolin-1, Dynamin 2, Flotillin-1, Clathrin, PIP5Kα and CDC42. Knockdown of Caveolin-1 reduces endocytosis of superparamagnetic iron oxide nanoparticles (SPIONs and silica-coated iron oxide nanoparticles (SCIONs between 23 and 41%, depending on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis in HeLa cells of iron oxide nanoparticles, used in this study, is mainly mediated by Caveolin-1 and CDC42. It is shown here for the first time, which proteins of the endocytotic pathway mediate the endocytosis of silica-coated iron oxide nanoparticles in HeLa cells in vitro. In future studies more experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles.

The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.

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Christal A Worthen

2014-03-01

Full Text Available Fine tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron-sensor, transferrin receptor 2 (TfR2, is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH. With the loss of functional TfR2, the liver produces about two-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin in the bloodstream, and hepatocytes treated with transferrin respond with a two-fold increase in hepcidin expression through stimulation of the BMP-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein (HFE, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

Vitreous Humor Changes Expression of Iron-Handling Proteins in Lens Epithelial Cells

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Goralska, Malgorzata; Fleisher, Lloyd N.; McGahan, M. Christine

2017-01-01

Purpose In humans, vitrectomy is associated with development of nuclear cataracts. Iron catalyzes free radical formation causing oxidative damage, which is implicated in cataract formation. This study was designed to determine if vitreous humor, which can initiate differentiation of lens epithelial cells, would have an effect on iron-handling proteins. Methods Cultured canine lens epithelial cells were treated with collected canine vitreous humor. Lysates of treated and control cells were separated by SDS-PAGE. Ferritin H- and L-chains, transferrin receptor 1, and aquaporin 0 were immunodetected and quantitated with specific antibodies. Morphologic changes in treated cells were assessed. Results Treatment of lens epithelial cells with a 33% (vol/vol) solution of vitreous humor changed the morphology of lens cells and induced expression of aquaporin 0, a marker of fiber cell differentiation that was undetectable in control cells. Treatment did not modify the size of iron-handling proteins but significantly increased content of ferritin from 2.9- to 8.8-fold over control and decreased levels of transferrin receptor by 37% to 59%. Conclusions Vitreous humor may significantly limit iron uptake by transferrin/transferrin receptor pathway, and by increasing ferritin levels could profoundly increase the iron-storage capacity of ferritin in lens cells. Vitreous humor may play a significant protective role against iron-catalyzed oxidative damage of lens epithelial cells and therefore in the formation of cataracts. PMID:28245299

Polyaminoquinoline iron chelators for vectorization of antiproliferative agents: design, synthesis, and validation.

Science.gov (United States)

Corcé, Vincent; Morin, Emmanuelle; Guihéneuf, Solène; Renault, Eric; Renaud, Stéphanie; Cannie, Isabelle; Tripier, Raphaël; Lima, Luís M P; Julienne, Karine; Gouin, Sébastien G; Loréal, Olivier; Deniaud, David; Gaboriau, François

2012-09-19

Iron chelation in tumoral cells has been reported as potentially useful during antitumoral treatment. Our aim was to develop new polyaminoquinoline iron chelators targeting tumoral cells. For this purpose, we designed, synthesized, and evaluated the biological activity of a new generation of iron chelators, which we named Quilamines, based on an 8-hydroxyquinoline (8-HQ) scaffold linked to linear polyamine vectors. These were designed to target tumor cells expressing an overactive polyamine transport system (PTS). A set of Quilamines bearing variable polyamine chains was designed and assessed for their ability to interact with iron. Quilamines were also screened for their cytostatic/cytotoxic effects and their selective uptake by the PTS in the CHO cell line. Our results show that both the 8-HQ moiety and the polyamine part participate in the iron coordination. HQ1-44, the most promising Quilamine identified, presents a homospermidine moiety and was shown to be highly taken up by the PTS and to display an efficient antiproliferative activity that occurred in the micromolar range. In addition, cytotoxicity was only observed at concentrations higher than 100 μM. We also demonstrated the high complexation capacity of HQ1-44 with iron while much weaker complexes were formed with other cations, indicative of a high selectivity. We applied the density functional theory to study the binding energy and the electronic structure of prototypical iron(III)-Quilamine complexes. On the basis of these calculations, Quilamine HQ1-44 is a strong tridentate ligand for iron(III) especially in the form of a 1:2 complex.

Policies for biosimilar uptake in Europe: An overview.

Science.gov (United States)

Moorkens, Evelien; Vulto, Arnold G; Huys, Isabelle; Dylst, Pieter; Godman, Brian; Keuerleber, Simon; Claus, Barbara; Dimitrova, Maria; Petrova, Guenka; Sović-Brkičić, Ljiljana; Slabý, Juraj; Šebesta, Robin; Laius, Ott; Karr, Allan; Beck, Morgane; Martikainen, Jaana E; Selke, Gisbert W; Spillane, Susan; McCullagh, Laura; Trifirò, Gianluca; Vella Bonanno, Patricia; Mack, Asbjørn; Fogele, Antra; Viksna, Anita; Władysiuk, Magdalena; Mota-Filipe, Helder; Meshkov, Dmitry; Kalaba, Marija; Mencej Bedrač, Simona; Fürst, Jurij; Zara, Corrine; Skiöld, Peter; Magnússon, Einar; Simoens, Steven

2017-01-01

Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further

Surface decoration of amine-rich carbon nitride with iron nanoparticles for arsenite (As{sup III}) uptake: The evolution of the Fe-phases under ambient conditions

Energy Technology Data Exchange (ETDEWEB)

Georgiou, Y., E-mail: yiannisgeorgiou@hotmail.com [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Mouzourakis, E., E-mail: emouzou@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Bourlinos, A.B., E-mail: bourlino@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Regional Centre of Advanced Technologies and Materials, Faculty of Science, Department of Physical Chemistry and Experimental Physics, Palacky University in Olomouc, 77146 (Czech Republic); Zboril, R., E-mail: radek.zboril@upol.cz [Regional Centre of Advanced Technologies and Materials, Faculty of Science, Department of Physical Chemistry and Experimental Physics, Palacky University in Olomouc, 77146 (Czech Republic); Karakassides, M.A., E-mail: mkarakas@cc.uoi.gr [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece); Douvalis, A.P., E-mail: adouval@uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Bakas, Th., E-mail: tbakas@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece); Deligiannakis, Y., E-mail: ideligia@cc.uoi.gr [Physics Department, University of Ioannina, Ioannina 45110 (Greece)

2016-07-15

Highlights: • Novel hybrid based on carbon nitride and iron nanoparticles (gC{sub 3}N{sub 4}-rFe). • gC{sub 3}N{sub 4}-rFe superior As{sup III} sorbent(76.5 mg g{sup −1}). • Surface complexation modeling of As{sup III} adsorption. • Dual mode EPR,monitoring of Fe{sup 2+} and Fe{sup 3+} evolution. - Abstract: A novel hybrid material (gC{sub 3}N{sub 4}-rFe) consisting of amine-rich graphitic carbon nitride (gC{sub 3}N{sub 4}), decorated with reduced iron nanoparticles (rFe) is presented. XRD and TEM show that gC{sub 3}N{sub 4}-rFe bears aggregation-free Fe-nanoparticles (10 nm) uniformly dispersed over the gC{sub 3}N{sub 4} surface. In contrast, non-supported iron nanoparticles are strongly aggregated, with non-uniform size distribution (20–100 nm). {sup 57}Fe-Mössbauer spectroscopy, dual-mode electron paramagnetic resonance (EPR) and magnetization measurements, allow a detailed mapping of the evolution of the Fe-phases after exposure to ambient O{sub 2}. The as-prepared gC{sub 3}N{sub 4}-rFe bears Fe{sup 2+} and Fe° phases, however only after long exposure to ambient O{sub 2}, a Fe-oxide layer is formed around the Fe° core. In this [Fe°/Fe-oxide] core-shell configuration, the gC{sub 3}N{sub 4}-rFe hybrid shows enhanced As{sup III} uptake capacity of 76.5 mg g{sup −1}, i.e., ca 90% higher than the unmodified carbonaceous support, and 300% higher than the non-supported Fe-nanoparticles. gC{sub 3}N{sub 4}-rFe is a superior As{sup III} sorbent i.e., compared to its single counterparts or vs. graphite/graphite oxide or activated carbon analogues (11–36 mg g{sup −1}). The present results demonstrate that the gC{sub 3}N{sub 4} matrix is not simply a net that holds the particles, but rather an active component that determines particle formation dynamics and ultimately their redox profile, size and surface dispersion homogeneity.

Quality and Safety Assurance of Iron Casts and Manufacturing Processes

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Kukla S.

2016-06-01

Full Text Available The scope of this work focuses on the aspects of quality and safety assurance of the iron cast manufacturing processes. Special attention was given to the processes of quality control and after-machining of iron casts manufactured on automatic foundry lines. Due to low level of automation and huge work intensity at this stage of the process, a model area was established which underwent reorganization in accordance with the assumptions of the World Class Manufacturing (WCM. An analysis of work intensity was carried out and the costs were divided in order to identify operations with no value added, particularly at individual manufacturing departments. Also an analysis of ergonomics at work stations was carried out to eliminate activities that are uncomfortable and dangerous to the workers' health. Several solutions were proposed in terms of rationalization of work organization at iron cast after-machining work stations. The proposed solutions were assessed with the use of multi-criteria assessment tools and then the best variant was selected based on the assumed optimization criteria. The summary of the obtained results reflects benefits from implementation of the proposed solutions.

Actinide uptake by transferrin and ferritin metalloproteins

International Nuclear Information System (INIS)

Den Auwer, C.; Llorens, I.; Moisy, Ph.; Vidaud, C.; Goudard, F.; Barbot, C.; Solari, P.L.; Funke, H.

2005-01-01

In order to better understand the mechanisms of actinide uptake by specific biomolecules, it is essential to explore the intramolecular interactions between the cation and the protein binding site. Although this has long been done for widely investigated transition metals, very few studies have been devoted to complexation mechanisms of actinides by active chelation sites of metalloproteins. In this field, X-ray absorption spectroscopy has been extensively used as a structural and electronic metal cation probe. The two examples that are presented here are related to two metalloproteins in charge of iron transport and storage in eukaryote cells: transferrin and ferritin. U(VI)O 2 2+ , Np(IV) and Pu(IV) have been selected because of their possible role as contaminant from the geosphere. (orig.)

Variation for N Uptake System in Maize: Genotypic Response to N Supply

KAUST Repository

Garnett, Trevor; Plett, Darren; Conn, Vanessa; Conn, Simon; Rabie, Huwaida; Rafalski, J. Antoni; Dhugga, Kanwarpal; Tester, Mark A.; Kaiser, Brent N.

2015-01-01

An understanding of the adaptations made by plants in their nitrogen (N) uptake systems in response to reduced N supply is important to the development of cereals with enhanced N uptake efficiency (NUpE). Twenty seven diverse genotypes of maize (Zea mays, L.) were grown in hydroponics for 3 weeks with limiting or adequate N supply. Genotypic response to N was assessed on the basis of biomass characteristics and the activities of the nitrate (NO−3) and ammonium (NH+4) high-affinity transport systems. Genotypes differed greatly for the ability to maintain biomass with reduced N. Although, the N response in underlying biomass and N transport related characteristics was less than that for biomass, there were clear relationships, most importantly, lines that maintained biomass at reduced N maintained net N uptake with no change in size of the root relative to the shoot. The root uptake capacity for both NO−3 and NH+4 increased with reduced N. Transcript levels of putative NO−3 and NH+4 transporter genes in the root tissue of a subset of the genotypes revealed that predominately ZmNRT2 transcript levels responded to N treatments. The correlation between the ratio of transcripts of ZmNRT2.2 between the two N levels and a genotype's ability to maintain biomass with reduced N suggests a role for these transporters in enhancing NUpE. The observed variation in the ability to capture N at low N provides scope for both improving NUpE in maize and also to better understand the N uptake system in cereals.

Variation for N Uptake System in Maize: Genotypic Response to N Supply

KAUST Repository

Garnett, Trevor

2015-11-09

An understanding of the adaptations made by plants in their nitrogen (N) uptake systems in response to reduced N supply is important to the development of cereals with enhanced N uptake efficiency (NUpE). Twenty seven diverse genotypes of maize (Zea mays, L.) were grown in hydroponics for 3 weeks with limiting or adequate N supply. Genotypic response to N was assessed on the basis of biomass characteristics and the activities of the nitrate (NO−3) and ammonium (NH+4) high-affinity transport systems. Genotypes differed greatly for the ability to maintain biomass with reduced N. Although, the N response in underlying biomass and N transport related characteristics was less than that for biomass, there were clear relationships, most importantly, lines that maintained biomass at reduced N maintained net N uptake with no change in size of the root relative to the shoot. The root uptake capacity for both NO−3 and NH+4 increased with reduced N. Transcript levels of putative NO−3 and NH+4 transporter genes in the root tissue of a subset of the genotypes revealed that predominately ZmNRT2 transcript levels responded to N treatments. The correlation between the ratio of transcripts of ZmNRT2.2 between the two N levels and a genotype\\'s ability to maintain biomass with reduced N suggests a role for these transporters in enhancing NUpE. The observed variation in the ability to capture N at low N provides scope for both improving NUpE in maize and also to better understand the N uptake system in cereals.

Study of /sup 201/Tl uptake by bone and bone marrow on /sup 201/Tl scintigraphy. With special reference to bone marrow abnormalities

Energy Technology Data Exchange (ETDEWEB)

Fujii, Tadashige; Tanaka, Masao; Hirose, Yoshiki; Hirayama, Jiro; Handa, Kenjiro; Nakanishi, Fumiko; Yano, Kesato; Ueda, Hitoshi

1989-04-01

Thallium-201 (Tl-201) uptake in the bone and bone marrow was examined in a total of 93 patients with various diseases. Sternal uptake of Tl-201 was observed when patients had bone marrow abnormality especially associated with hematopoietic disease. It was associated with proliferation of immature cells and of various types of bone marrow cells, especially erythroblastic and plasma cells. Whole-body Tl-201 scanning showed a high uptake (82%) in the sternum, chest, lumbar vertebrae, and pelvis. Thallium-201 was definitively taken up by the sternum in polycythemia (5/41), hemolytic anemia (2/2), iron deficiency anemia (2/2), and multiple myeloma (2/5). For leukemia, Tl-201 uptake was slight or negative. Thallium-201 scanning proved useful in visualizing bone marrow abnormality, although careful interpretation of bone and bone marrow uptake is required. (Namekawa, K).

Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

LENUS (Irish Health Repository)

McGrath, T

2018-01-01

We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

Enhanced ferrihydrite dissolution by a unicellular, planktonic cyanobacterium: a biological contribution to particulate iron bioavailability.

Science.gov (United States)

Kranzler, Chana; Kessler, Nivi; Keren, Nir; Shaked, Yeala

2016-12-01

Iron (Fe) bioavailability, as determined by its sources, sinks, solubility and speciation, places severe environmental constraints on microorganisms in aquatic environments. Cyanobacteria are a widespread group of aquatic, photosynthetic microorganisms with especially high iron requirements. While iron exists predominantly in particulate form, little is known about its bioavailability to cyanobacteria. Some cyanobacteria secrete iron solubilizing ligands called siderophores, yet many environmentally relevant strains do not have this ability. This work explores the bioavailability of amorphous synthetic Fe-oxides (ferrihydrite) to the non-siderophore producing, unicellular cyanobacterium, Synechocystis sp PCC 6803. Iron uptake assays with 55 ferrihydrite established dissolution as a critical prerequisite for iron transport. Dissolution assays with the iron binding ligand, desferrioxamine B, demonstrated that Synechocystis 6803 enhances ferrihydrite dissolution, exerting siderophore-independent biological influence on ferrihydrite bioavailability. Dissolution mechanisms were studied using a range of experimental conditions; both cell-particle physical proximity and cellular electron flow were shown to be important determinants of bio-dissolution by Synechocystis 6803. Finally, the effects of ferrihydrite stability on bio-dissolution rates and cell physiology were measured, integrating biological and chemical aspects of ferrihydrite bioavailability. Collectively, these findings demonstrate that Synechocystis 6803 actively dissolves ferrihydrite, highlighting a significant biological component to mineral phase iron bioavailability in aquatic environments. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Influence of silicon treatment on antimony uptake and translocation in rice genotypes with different radial oxygen loss.

Science.gov (United States)

Zhang, Liping; Yang, Qianqian; Wang, Shiliang; Li, Wanting; Jiang, Shaoqing; Liu, Yan

2017-10-01

Antimony (Sb) pollution in soil may have a negative impact on the health of people consuming rice. This study investigated the effect of silicon (Si) application on rice biomass, iron plaque formation, and Sb uptake and speciation in rice plants with different radial oxygen loss (ROL) using pot experiments. The results demonstrated that Si addition increased the biomass of straw and grain, but had no obvious impact on the root biomass. Indica genotypes with higher ROL underwent greater iron plaque formation and exhibited more Sb sequestration in iron plaque. Silicon treatments increased iron levels in iron plaque from the different genotypes but decreased the total Sb concentration in root, straw, husk, and grain. In addition, Si treatment reduced the inorganic Sb concentrations but slightly increased the trimethylantimony (TMSb) concentrations in rice straw. Moreover, rice straw from hybrid genotypes accumulated higher concentrations of TMSb and inorganic Sb than that from indica genotypes. The conclusions from this study indicate that Sb contamination in rice can be efficiently reduced by applying Si treatment and selecting genotypes with high ROL. Copyright © 2017 Elsevier Inc. All rights reserved.

Iron Fertilization of the Southern Ocean: Regional Simulation and Analysis of C-Sequestration in the Ross Sea

Energy Technology Data Exchange (ETDEWEB)

Kevin Arrigo

2012-03-13

A modified version of the dynamic 3-dimensional mesoscale Coupled Ice, Atmosphere, and Ocean model (CIAO) of the Ross Sea ecosystem has been used to simulate the impact of environmental perturbations upon primary production and biogenic CO2 uptake. The Ross Sea supports two taxonomically, and spatially distinct phytoplankton populations; the haptophyte Phaeocystis antarctica and diatoms. Nutrient utilization ratios predict that P. antarctica and diatoms will be driven to nitrate and phosphate limitation, respectively. Model and field data have confirmed that the Ross Sea is iron limited with only two-thirds of the macronutrients consumed by the phytoplankton by the end of the growing season. In this study, the CIAO model was improved to simulate a third macronutrient (phosphate), dissolved organic carbon, air-sea gas exchange, and the carbonate system. This enabled us to effectively model pCO2 and subsequently oceanic CO2 uptake via gas exchange, allowing investigations into the affect of alleviating iron limitation on both pCO2 and nutrient drawdown.

Scope Definition

DEFF Research Database (Denmark)

Bjørn, Anders; Owsianiak, Mikołaj; Laurent, Alexis

2018-01-01

The scope definition is the second phase of an LCA. It determines what product systems are to be assessed and how this assessment should take place. This chapter teaches how to perform a scope definition. First, important terminology and key concepts of LCA are introduced. Then, the nine items...... making up a scope definition are elaborately explained: (1) Deliverables. (2) Object of assessment, (3) LCI modelling framework and handling of multifunctional processes, (4) System boundaries and completeness requirements, (5) Representativeness of LCI data, (6) Preparing the basis for the impact...... assessment, (7) Special requirements for system comparisons, (8) Critical review needs and (9) Planning reporting of results. The instructions relate both to the performance and reporting of a scope definition and are largely based on ILCD....

Iron availability, nitrate uptake, and exportable new production in the subarctic Pacific. [phytoplankton population growth support and atmospheric CO2 removal

Science.gov (United States)

Banse, Karl

1991-01-01

This paper presents a critique of experimental data and papers by Martin et al. (1989, 1990), who suggested that the phytoplankton growth is iron-limited and that, small additions of iron to large subarctic ocean areas might be a way of removing significant amounts of atmospheric CO2 by increasing phytoplancton growth. Data are presented to show that, in the summer of 1987, the phytoplankton assemblage as a whole was not iron limited, as measured by the bulk removal of nitrate or by the increase of chlorophyll. It is suggested that grazing normally prevents the phytoplankton from reaching concentrations that reduce the iron (and nitrate) to levels that depress division rates drastically.

The PICALM protein plays a key role in iron homeostasis and cell proliferation.

Directory of Open Access Journals (Sweden)

Paula B Scotland

Full Text Available The ubiquitously expressed phosphatidylinositol binding clathrin assembly (PICALM protein associates with the plasma membrane, binds clathrin, and plays a role in clathrin-mediated endocytosis. Alterations of the human PICALM gene are present in aggressive hematopoietic malignancies, and genome-wide association studies have recently linked the PICALM locus to late-onset Alzheimer's disease. Inactivating and hypomorphic Picalm mutations in mice cause different degrees of severity of anemia, abnormal iron metabolism, growth retardation and shortened lifespan. To understand PICALM's function, we studied the consequences of PICALM overexpression and characterized PICALM-deficient cells derived from mutant fit1 mice. Our results identify a role for PICALM in transferrin receptor (TfR internalization and demonstrate that the C-terminal PICALM residues are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TfR internalization. Murine embryonic fibroblasts (MEFs that are deficient in PICALM display several characteristics of iron deficiency (increased surface TfR expression, decreased intracellular iron levels, and reduced cellular proliferation, all of which are rescued by retroviral PICALM expression. The proliferation defect of cells that lack PICALM results, at least in part, from insufficient iron uptake, since it can be corrected by iron supplementation. Moreover, PICALM-deficient cells are particularly sensitive to iron chelation. Taken together, these data reveal that PICALM plays a critical role in iron homeostasis, and offer new perspectives into the pathogenesis of PICALM-associated diseases.

Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias

International Nuclear Information System (INIS)

Muta, K.; Nishimura, J.; Ideguchi, H.; Umemura, T.; Ibayashi, H.

1987-01-01

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125 I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects. Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125 I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast

Fe uptake from meso and D,L-racemic Fe(o,o-EDDHA) isomers by strategy I and II plants.

Science.gov (United States)

Cerdán, Mar; Alcañiz, Sara; Juárez, Margarita; Jordá, Juana D; Bermúdez, Dolores

2006-02-22

One of the most efficient fertilizers to correct Fe deficiency in calcareous soils and waters with high bicarbonate content is based on ferric ethylenediamine-N,N'-bis(o-hydroxyphenylacetic) acid [Fe(o,o-EDDHA)]. Fe(o,o-EDDHA) forms two groups of geometric isomers known as meso and D,L-racemic. To determine the Fe uptake from meso and D,L-racemic Fe(o,o-EDDHA), four iron-efficient plants, two plants representative of strategy I (tomato and pepper) and two plants representative of strategy II (wheat and oats), were grown in hydroponic culture. Results indicated that strategy II plants took up iron from both Fe(o,o-EDDHA) isomers equally. However, strategy I plants took mainly the iron associated with the meso form (the lowest stability isomer).

Impact of two iron(III) chelators on the iron, cadmium, lead and nickel accumulation in poplar grown under heavy metal stress in hydroponics.

Science.gov (United States)

Mihucz, Victor G; Csog, Árpád; Fodor, Ferenc; Tatár, Enikő; Szoboszlai, Norbert; Silaghi-Dumitrescu, Luminiţa; Záray, Gyula

2012-04-15

Poplar (Populus jacquemontiana var. glauca cv. Kopeczkii) was grown in hydroponics containing 10 μM Cd(II), Ni(II) or Pb(II), and Fe as Fe(III) EDTA or Fe(III) citrate in identical concentrations. The present study was designed to compare the accumulation and distribution of Fe, Cd, Ni and Pb within the different plant compartments. Generally, Fe and heavy-metal accumulation were higher by factor 2-7 and 1.6-3.3, respectively, when Fe(III) citrate was used. Iron transport towards the shoot depended on the Fe(III) chelate and, generally, on the heavy metal used. Lead was accumulated only in the root. The amounts of Fe and heavy metals accumulated by poplar were very similar to those of cucumber grown in an identical way, indicating strong Fe uptake regulation of these two Strategy I plants: a cultivar and a woody plant. The Strategy I Fe uptake mechanism (i.e. reducing Fe(III) followed by Fe(II) uptake), together with the Fe(III) chelate form in the nutrient solution had significant effects on Fe and heavy metal uptake. Poplar appears to show phytoremediation potential for Cd and Ni, as their transport towards the shoot was characterized by 51-54% and 26-48% depending on the Fe(III) supply in the nutrient solution. Copyright © 2012 Elsevier GmbH. All rights reserved.

Full-scope training simulators

International Nuclear Information System (INIS)

Ugedo, E.

1986-01-01

The following topics to be covered in this report are: Reasons justifying the use of full-scope simulators for operator qualification. Full-scope simulator description: the control room, the physical models, the computer complex, the instructor's console. Main features of full-scope simulators. Merits of simulator training. The role of full-scope simulators in the training programs. The process of ordering and acquiring a full-scope simulator. Maintaining and updating simulator capabilities. (orig./GL)

Genome-based analysis of heme biosynthesis and uptake in prokaryotic systems.

Science.gov (United States)

Cavallaro, Gabriele; Decaria, Leonardo; Rosato, Antonio

2008-11-01

Heme is the prosthetic group of many proteins that carry out a variety of key biological functions. In addition, for many pathogenic organisms, heme (acquired from the host) may constitute a very important source of iron. Organisms can meet their heme demands by taking it up from external sources, by producing the cofactor through a dedicated biosynthetic pathway, or both. Here we analyzed the distribution of proteins specifically involved in the processes of heme biosynthesis and heme uptake in 474 prokaryotic organisms. These data allowed us to identify which organisms are capable of performing none, one, or both processes, based on the similarity to known systems. Some specific instances where one or more proteins along the pathways had unusual modifications were singled out. For two key protein domains involved in heme uptake, we could build a series of structural models, which suggested possible alternative modes of heme binding. Future directions for experimental work are given.

PROJECT SCOPE MANAGEMENT PROCESS

Directory of Open Access Journals (Sweden)

Yana Derenskaya

2018-01-01

Full Text Available The purpose of the article is to define the essence of project scope management process, its components, as well as to develop an algorithm of project scope management in terms of pharmaceutical production. Methodology. To carry out the study, available information sources on standards of project management in whole and elements of project scope management in particular are analysed. Methods of system and structural analysis, logical generalization are used to study the totality of subprocesses of project scope management, input and output documents, and to provide each of them. Methods of network planning are used to construct a precedence diagram of project scope management process. Results of the research showed that components of the project scope management are managing the scope of the project product and managing the content of project work. It is the second component is investigated in the presented work as a subject of research. Accordingly, it is defined that project scope management process is to substantiate and bring to the realization the necessary amount of work that ensures the successful implementation of the project (achievement of its goal and objectives of individual project participants. It is also determined that the process of managing the project scope takes into account the planning, definition of the project scope, creation of the structure of project work, confirmation of the scope and management of the project scope. Participants of these subprocesses are: customer, investor, and other project participants – external organizations (contractors of the project; project review committee; project manager and project team. It is revealed that the key element of planning the project scope is the formation of the structure of design work, the justification of the number of works, and the sequence of their implementation. It is recommended to use the following sequence of stages for creating the structure of project work

Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

Science.gov (United States)

Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

2018-01-01

Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

Absorption of manganese and iron in a mouse model of hemochromatosis.

Directory of Open Access Journals (Sweden)

Jonghan Kim

Full Text Available Hereditary hemochromatosis, an iron overload disease associated with excessive intestinal iron absorption, is commonly caused by loss of HFE gene function. Both iron and manganese absorption are regulated by iron status, but the relationships between the transport pathways of these metals and how they are affected by HFE-associated hemochromatosis remain poorly understood. Loss of HFE function is known to alter the intestinal expression of DMT1 (divalent metal transporter-1 and Fpn (ferroportin, transporters that have been implicated in absorption of both iron and manganese. Although the influence of HFE deficiency on dietary iron absorption has been characterized, potential effects on manganese metabolism have yet to be explored. To investigate the role of HFE in manganese absorption, we characterized the uptake and distribution of the metal in Hfe (-/- knockout mice after intravenous, intragastric, and intranasal administration of (54Mn. These values were compared to intravenous and intragastric administration of (59Fe. Intestinal absorption of (59Fe was increased and clearance of injected (59Fe was also increased in Hfe(-/- mice compared to controls. Hfe (-/- mice displayed greater intestinal absorption of (54Mn compared to wild-type Hfe(+/+ control mice. After intravenous injection, the distribution of (59Fe to heart and liver was greater in Hfe (-/- mice but no remarkable differences were observed for (54Mn. Although olfactory absorption of (54Mn into blood was unchanged in Hfe (-/- mice, higher levels of intranasally-instilled (54Mn were associated with Hfe(-/- brain compared to controls. These results show that manganese transport and metabolism can be modified by HFE deficiency.

Genetics Home Reference: iron-refractory iron deficiency anemia

Science.gov (United States)

... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

Optimal copper supply is required for normal plant iron deficiency responses

OpenAIRE

Waters, Brian M; Armbrust, Laura C

2013-01-01

Iron (Fe) and copper (Cu) homeostasis are tightly linked across biology. Understanding crosstalk between Fe and Cu nutrition could lead to strategies for improved growth on soils with low or excess metals, with implications for agriculture and phytoremediation. Here, we show that Cu and Fe nutrition interact to increase or decrease Fe and/or Cu accumulation in leaves and Fe uptake processes. Leaf Cu concentration increased under low Fe supply, while high Cu lowered leaf Fe concentration. Ferr...

Effect of dietary iron source and iron status on iron bioavailability tests in the rat

International Nuclear Information System (INIS)

Zhang, D.; Hendricks, D.G.; Mahoney, A.W.

1986-01-01

Weanling male rats were made anemic in 7 days by feeding a low iron diet and bleeding. Healthy rats were fed the low iron diet supplemented with ferrous sulfate (29 ppm Fe). Each group was subdivided and fed for 10 days on test diets containing about 29 ppm iron that were formulated with meat:spinach mixtures or meat:soy mixtures to provided 100:0, 75:25, 50:50, 25:75, or 0:100% of the dietary iron from these sources or from a ferrous sulfate diet. After 3 days on the diets all rats were dosed orally with 2 or 5 micro curries of 59 Fe after a 18 hour fast and refeeding for 1.5 hours. Iron status influenced liver iron, carcass iron, liver radio activity and percent of radioactive dose retained. Diet influenced fecal iron and apparent absorption of iron. In iron bioavailability studies assessment methodology and iron status of the test subject greatly influences the estimates of the value of dietary sources of iron

Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

Science.gov (United States)

Aznar, Aude; Chen, Nicolas W.G.; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

2014-01-01

Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H2O2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001

The treatment of iron deficiency without anaemia (in otherwise healthy persons).

Science.gov (United States)

Clénin, German E

2017-06-21

Iron deficiency is the most widespread and frequent nutritional disorder in the world. It affects a high proportion of children and women in developing countries and is also significantly prevalent in the industrialised world, with a clear predominance in adolescents and menstruating females. Iron is essential for optimal cognitive function and physical performance, not only as a binding site of oxygen but also as a critical constituent of many enzymes. Therefore iron deficiency at all its levels - nonanaemic iron deficiency, iron deficiency with microcytosis or hypochromia and iron deficiency anaemia - should be treated. In the presence of normal stores, however, preventative iron administration is inefficient, has side effects and seems to be harmful. In symptomatic patients with fatigue or in a population at risk for iron deficiency (adolescence, heavy or prolonged menstruation, high performance sport, vegetarian or vegan diet, eating disorder, underweight), a baseline set of blood tests including haemoglobin concentration, haematocrit, mean cellular volume, mean cellular haemoglobin, percentage of hypochromic erythrocytes and serum ferritin levels are important to monitor iron deficiency. To avoid false negative results (high ferritin levels in spite of iron deficiency), an acute phase reaction should be excluded by history and measurement of C-reactive protein. An algorithm leads through this diagnostic process and the decision making for a possible treatment. For healthy males and females aged >15 years, a ferritin cut-off of 30 µg/l is appropriate. For children from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 µg/l, respectively, are recommended. As a first step in treatment, counselling and oral iron therapy are usually combined. Integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial. In order to prevent reduced compliance, mainly as a result of

Iron-Catalyzed C-O Bond Activation: Opportunity for Sustainable Catalysis.

Science.gov (United States)

Bisz, Elwira; Szostak, Michal

2017-10-23

Oxygen-based electrophiles have emerged as some of the most valuable cross-coupling partners in organic synthesis due to several major strategic and environmental benefits, such as abundance and potential to avoid toxic halide waste. In this context, iron-catalyzed C-O activation/cross-coupling holds particular promise to achieve sustainable catalytic protocols due to its natural abundance, inherent low toxicity, and excellent economic and ecological profile. Recently, tremendous progress has been achieved in the development of new methods for functional-group-tolerant iron-catalyzed cross-coupling reactions by selective C-O cleavage. These methods establish highly attractive alternatives to traditional cross-coupling reactions by using halides as electrophilic partners. In particular, new easily accessible oxygen-based electrophiles have emerged as substrates in iron-catalyzed cross-coupling reactions, which significantly broaden the scope of this catalysis platform. New mechanistic manifolds involving iron catalysis have been established; thus opening up vistas for the development of a wide range of unprecedented reactions. The synthetic potential of this sustainable mode of reactivity has been highlighted by the development of new strategies in the construction of complex motifs, including in target synthesis. The most recent advances in sustainable iron-catalyzed cross-coupling of C-O-based electrophiles are reviewed, with a focus on both mechanistic aspects and synthetic utility. It should be noted that this catalytic manifold provides access to motifs that are often not easily available by other methods, such as the assembly of stereodefined dienes or C(sp 2 )-C(sp 3 ) cross-couplings, thus emphasizing the synthetic importance of this mode of reactivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis, iron(III) complexation properties, molecular dynamics simulations and P. aeruginosa siderophore-like activity of two pyoverdine analogs.

Science.gov (United States)

Antonietti, Viviane; Boudesocque, Stéphanie; Dupont, Laurent; Farvacques, Natacha; Cézard, Christine; Da Nascimento, Sophie; Raimbert, Jean-François; Socrier, Larissa; Robin, Thierry-Johann; Morandat, Sandrine; El Kirat, Karim; Mullié, Catherine; Sonnet, Pascal

2017-09-08

P. aeruginosa ranks among the top five organisms causing nosocomial infections. Among the many novel strategies for developing new therapeutics against infection, targeting iron uptake mechanism seems promising as P. aeruginosa needs iron for its growth and survival. To scavenge iron, the bacterium produces siderophores possessing a very high affinity towards Fe(III) ions such as pyoverdines. In this work, we decided to study two pyoverdine analogs, aPvd2 and aPvd3, structurally close to the endogen pyoverdine. The pFe constants calculated with the values of formation showed a high affinity of aPvd3 towards Fe(III). Molecular dynamics calculations demonstrated that aPvd3-Fe forms with Fe(III) stable 1:1 complexes in water, whereas aPvd2 does not. Only aPvd3 is able to increase the bacterial growth and represents thus an alternative to pyoverdine for iron acquisition by the bacterium. The aPvd2-3 interaction studies with a lipid membrane indicated that they were unable to interact and to cross the plasma membrane of bacteria by passive diffusion. Consequently, the penetration of aPvd3 is ruled by a transport membrane protein. These results showed that aPvd3 may be used to inhibit pyoverdine uptake or to promote the accumulation and release of antibiotics into the cell following a Trojan horse strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Speciation And Uptake of Arsenic Accumulated By Corn Seedlings Using XAS And DRC-ICP-MS

Energy Technology Data Exchange (ETDEWEB)

Parsons, J.G.; Martinez-Martinez, A.; Peralta-Videa, J.R.; Gardea-Torresdey, J.L.

2009-05-21

ICP-MS was used to investigate the uptake of As(III) and As(V) from hydroponics growth media by corn seedlings. It was found that arsenic uptake by the plant roots for the arsenic(V) and arsenic(III) treatments were 95 and 112 ppm, respectively. However, in the shoots of the arsenic (V) treatments had 18 ppm whereas arsenic(III) treatments had 12 ppm. XANES studies showed that As for both treatments arsenic was present as a mixture of an As(III) sulfur complex and an As(V) oxygen complex. The XANES data was corroborated by the EXAFS studies showing the presence of both oxygen and sulfur ligands coordinated to the arsenic. Iron concentrations were found to increase by 4 fold in the As(V) contaminated growth media and 7 fold in the As(III) treatment compared to the control iron concentration of 500 ppm. Whereas, the total iron concentration in the shoots was found to decrease by approximately the same amount for both treatments from 360 ppm in the control to approximately 125 ppm in both arsenic treatments. Phosphorus concentrations were found to decrease in both the roots and shoots compared to the control plants. The total sulfur in the roots was found to increase in the arsenic(III) and arsenic(V) treatments to 560 ppm and 800 ppm, respectively, compared to the control plants 358 ppm. In addition, the total sulfur in shoots of the plants was found to remain relatively constant at approximately 1080 ppm. The potassium concentrations in the plants were found to increase in the roots and decrease in the shoots.

Iron absorption in relation to iron status

International Nuclear Information System (INIS)

Magnusson, B.; Bjoern-Rasmussen, E.; Hallberg, L.; Rossander, L.

1981-01-01

The absorption from a 3 mg dose of ferrous iron was measured in 250 male subjects. The absorption was related to the log concentration of serum ferritin in 186 subjects of whom 99 were regular blood donors (r= -0.76), and to bone marrow haemosiderin grading in 52 subjects with varying iron status. The purpose was to try and establish a percentage absorption from such a dose that is representative of subjects who are borderline iron deficient. This information is necessary for food iron absorption studies in order (1) to calculate the absorption of iron from the diet at a given iron status and (2) compare the absorption of iron from different meals studied in different groups of subjects by different investigarors. The results suggest that an absorption of about 40% of a 3 mg reference dose of ferrous iron is given in a fasting state, roughly corresponds to the absorption in borderline-iron-deficient subjects. The results indicate that this 40% absorption value corresponds to a serum ferritin level of 30 μg/l and that food iron absorption in a group of subjects should be expressed preferably as the absorption corresponding to a reference-dose absorption of 45%, or possibly a serum ferritin level of 30 μg/l. (author)

Iron deficiency anemia in an athlete associated with Campylobacter pylori-negative chronic gastritis

International Nuclear Information System (INIS)

Mack, D.; Sherman, P.

1989-01-01

A 14-year-old athletic boy with a 1-year history of decreased exercise tolerance presented with unexplained iron deficiency anemia. Panendoscopy, colonoscopy, and barium contrast studies of the gastrointestinal tract were normal. However, persistent uptake of radionuclide using a 99m technetium-sucralfate scan suggested inflammation localized to the stomach. Mucosal biopsies demonstrated acute and chronic gastritis that was not associated with the presence of Campylobacter pylori

Standard Practice for Characterizing Neutron Exposures in Iron and Low Alloy Steels in Terms of Displacements Per Atom (DPA), E 706(ID)

CERN Document Server

American Society for Testing and Materials. Philadelphia

2001-01-01

1.1 This practice describes a standard procedure for characterizing neutron irradiations of iron (and low alloy steels) in terms of the exposure index displacements per atom (dpa) for iron. 1.2 Although the general procedures of this practice apply to any material for which a displacement cross section d(E) is known (see Practice E 521), this practice is written specifically for iron. 1.3 It is assumed that the displacement cross section for iron is an adequate approximation for calculating displacements in steels that are mostly iron (95 to 100 %) in radiation fields for which secondary damage processes are not important. 1.4 Procedures analogous to this one can be formulated for calculating dpa in charged particle irradiations. (See Practice E 521.) 1.5 The application of this practice requires knowledge of the total neutron fluence and flux spectrum. Refer to Practice E 521 for determining these quantities. 1.6 The correlation of radiation effects data is beyond the scope of this practice. This stand...

An iron-57 Moessbauer spectroscopic study of titania-supported iron- and iron-iridium catalysts

International Nuclear Information System (INIS)

Berry, F.J.; Jobson, S.

1992-01-01

57 Fe Moessbauer spectroscopy shows that titania-supported iron is reduced by treatment in hydrogen at significantly lower temperatures than corresponding silica- and alumina-supported catalysts. The metallic iron formed under hydrogen at 600deg C is partially converted to carbide by treatment in carbon monoxide and hydrogen. In contrast to its alumina- and silica-supported counterparts, the remainder of the titania-supported iron is unchanged by this gaseous mixture. The 57 Fe Moessbauer spectra of EXAFS show that iron and iridium in the titania-supported iron-iridium catalysts are reduced in hydrogen at even lower temperatures and, after treatment at 600deg C, are predominantly present as the iron-iridium alloy. The treatment of these reduced catalysts in carbon monoxide and hydrogen is shown by Moessbauer spectroscopy and EXAFS to induce the segregation of iron from the iron-iridium alloy and its conversion to iron oxide. (orig.)

HapX-Mediated Iron Homeostasis Is Essential for Rhizosphere Competence and Virulence of the Soilborne Pathogen Fusarium oxysporum[C][W][OA

Science.gov (United States)

López-Berges, Manuel S.; Capilla, Javier; Turrà, David; Schafferer, Lukas; Matthijs, Sandra; Jöchl, Christoph; Cornelis, Pierre; Guarro, Josep; Haas, Hubertus; Di Pietro, Antonio

2012-01-01

Soilborne fungal pathogens cause devastating yield losses and are highly persistent and difficult to control. During the infection process, these organisms must cope with limited availability of iron. Here we show that the bZIP protein HapX functions as a key regulator of iron homeostasis and virulence in the vascular wilt fungus Fusarium oxysporum. Deletion of hapX does not affect iron uptake but causes derepression of genes involved in iron-consuming pathways, leading to impaired growth under iron-depleted conditions. F. oxysporum strains lacking HapX are reduced in their capacity to invade and kill tomato (Solanum lycopersicum) plants and immunodepressed mice. The virulence defect of ΔhapX on tomato plants is exacerbated by coinoculation of roots with a biocontrol strain of Pseudomonas putida, but not with a siderophore-deficient mutant, indicating that HapX contributes to iron competition of F. oxysporum in the tomato rhizosphere. These results establish a conserved role for HapX-mediated iron homeostasis in fungal infection of plants and mammals. PMID:22968717

FLEXIBLE SCOPE IN ACCREDITATION - INTRODUCING VAGUENESS OR BETTER EXPRESSION OF SCOPE

Directory of Open Access Journals (Sweden)

Miloš Jelić

2007-09-01

Full Text Available Historically, laboratory accreditation has been grounded on fixed scope of accreditation to establish precisely and unambiguously the range of tests and calibrations covered by a granted accreditation. By the time elapsed it was noticed that such approach sometimes appears to be restrictive since it constrains new or modified methods to be added to a laboratory's scope, even where competence in this general area has already been demonstrated. Accreditation of a flexible scope places more of the responsibility onto the laboratory itself because it imposes to the laboratory to establish and maintain management system that can control its proposed approach. Flexible scope of accreditation yields benefit to all accreditation stakeholders but, on the other hand, introduces more requiring interpretations of relevant standard clauses and includes the bounds of the scope which are defined in more distinct way.

Does lead use the intestinal absorptive pathways of iron? Impact of iron status on murine 210Pb and 59Fe absorption in duodenum and ileum in vivo

International Nuclear Information System (INIS)

Elsenhans, Bernd; Janser, Heinz; Windisch, Wilhelm; Schuemann, Klaus

2011-01-01

Highlights: → Absorption of 210 Pb increases much less than that of 59 Fe in murine duodena. → 210 Pb-absorption is almost equally high in murine duodenal and ileal segments. → 59 Fe absorption is much lower in ileal than in duodenal segments. → There must be an additional DMT1-independet pathway for intestinal Pb absorption. -- Abstract: Background: Human isotope studies and epidemiological trials are controversial as to whether lead absorption shares the absorptive pathways of iron and whether body lead content can be reduced by iron supplementation. Aim: To compare the impact of iron-deficiency on 59 Fe- and 210 Pb-absorption rates in duodenal and ileal segments. Methods: 59 Fe- and 210 Pb-absorption was determined in ligated duodenal and ileal segments from juvenile and adult iron-deficient and iron-adequate C57Bl6 wild-type mice (n = 6) in vivo at luminal concentrations corresponding to human exposure (Fe: 1 and 100 μmol/L; Pb: 1 μmol/L). Results and discussion: 59 Fe-absorption increased 10-15-fold in iron-deficient duodena from adult and adolescent mice. Ileal 59 Fe-absorption was 4-6 times lower than in iron-adequate duodena showing no adaptation to iron-deficiency. This in accordance to expectation as the divalent metal transport 1 (DMT1) shows low ileal expression levels. Juvenile 59 Fe-absorption was about twice as high as in adult mice. In contrast, duodenal 210 Pb-absorption was increased only 1.5-1.8-fold in iron-deficiency in juvenile and adult mice and, again in contrast to 59 Fe, ileal 210 Pb-absorption was as high as in iron-adequate duodena. Conclusions: The findings suggest a DMT1-independent pathway to mediate lead absorption along the entire small intestine in addition to DMT1-mediated duodenal uptake. Ileal lead absorption appears substantial, due the much longer residence of ingesta in the distal small intestine. Differences in lead-solubility and -binding to luminal ligands can, thus, explain the conflicting findings regarding the

Erythroid cell mitochondria receive endosomal iron by a "kiss-and-run" mechanism.

Science.gov (United States)

Hamdi, Amel; Roshan, Tariq M; Kahawita, Tanya M; Mason, Anne B; Sheftel, Alex D; Ponka, Prem

2016-12-01

In erythroid cells, more than 90% of transferrin-derived iron enters mitochondria where ferrochelatase inserts Fe 2+ into protoporphyrin IX. However, the path of iron from endosomes to mitochondrial ferrochelatase remains elusive. The prevailing opinion is that, after its export from endosomes, the redox-active metal spreads into the cytosol and mysteriously finds its way into mitochondria through passive diffusion. In contrast, this study supports the hypothesis that the highly efficient transport of iron toward ferrochelatase in erythroid cells requires a direct interaction between transferrin-endosomes and mitochondria (the "kiss-and-run" hypothesis). Using a novel method (flow sub-cytometry), we analyze lysates of reticulocytes after labeling these organelles with different fluorophores. We have identified a double-labeled population definitively representing endosomes interacting with mitochondria, as demonstrated by confocal microscopy. Moreover, we conclude that this endosome-mitochondrion association is reversible, since a "chase" with unlabeled holotransferrin causes a time-dependent decrease in the size of the double-labeled population. Importantly, the dissociation of endosomes from mitochondria does not occur in the absence of holotransferrin. Additionally, mutated recombinant holotransferrin, that cannot release iron, significantly decreases the uptake of 59 Fe by reticulocytes and diminishes 59 Fe incorporation into heme. This suggests that endosomes, which are unable to provide iron to mitochondria, cause a "traffic jam" leading to decreased endocytosis of holotransferrin. Altogether, our results suggest that a molecular mechanism exists to coordinate the iron status of endosomal transferrin with its trafficking. Besides its contribution to the field of iron metabolism, this study provides evidence for a new intracellular trafficking pathway of organelles. Copyright © 2016 Elsevier B.V. All rights reserved.

Lead induced changes in growth and micronutrient uptake of Jatropha curcas L.

Science.gov (United States)

Shu, Xiao; Zhang, QuanFa; Wang, WeiBo

2014-11-01

Effects of lead treatment on growth and micronutrient uptake in Jatropha curcas L. seedlings were assessed by means of microcosm experiments. Results suggested that superoxide dismutase (SOD) activity increased with increasing lead concentration. There was significant positive correlation between lead treatment concentration and SOD and peroxidase activity. Catalase activity was initiated under lower lead stress but, was inhibited under higher lead exposure. Lead had a stimulating effect on seedlings height and leaf area at lower lead concentrations. The J. curcas can accumulate higher amounts of available lead from soil but can translocate only low amounts to the shoots. Results indicating SOD and peroxidase activity in J. curcas seedlings played an important role in resisting the oxidative stress induced by lead. The addition of lead significantly increased the content of zinc in plant tissue and enhanced the transport of iron from roots to shoots but contributed to a decrease in measured copper, iron, and manganese content.

Extracellular enzymes facilitate electron uptake in biocorrosion and bioelectrosynthesis.

Science.gov (United States)

Deutzmann, Jörg S; Sahin, Merve; Spormann, Alfred M

2015-04-21

Direct, mediator-free transfer of electrons between a microbial cell and a solid phase in its surrounding environment has been suggested to be a widespread and ecologically significant process. The high rates of microbial electron uptake observed during microbially influenced corrosion of iron [Fe(0)] and during microbial electrosynthesis have been considered support for a direct electron uptake in these microbial processes. However, the underlying molecular mechanisms of direct electron uptake are unknown. We investigated the electron uptake characteristics of the Fe(0)-corroding and electromethanogenic archaeon Methanococcus maripaludis and discovered that free, surface-associated redox enzymes, such as hydrogenases and presumably formate dehydrogenases, are sufficient to mediate an apparent direct electron uptake. In genetic and biochemical experiments, we showed that these enzymes, which are released from cells during routine culturing, catalyze the formation of H2 or formate when sorbed to an appropriate redox-active surface. These low-molecular-weight products are rapidly consumed by M. maripaludis cells when present, thereby preventing their accumulation to any appreciable or even detectable level. Rates of H2 and formate formation by cell-free spent culture medium were sufficient to explain the observed rates of methane formation from Fe(0) and cathode-derived electrons by wild-type M. maripaludis as well as by a mutant strain carrying deletions in all catabolic hydrogenases. Our data collectively show that cell-derived free enzymes can mimic direct extracellular electron transfer during Fe(0) corrosion and microbial electrosynthesis and may represent an ecologically important but so far overlooked mechanism in biological electron transfer. The intriguing trait of some microbial organisms to engage in direct electron transfer is thought to be widespread in nature. Consequently, direct uptake of electrons into microbial cells from solid surfaces is assumed

Policies for biosimilar uptake in Europe: An overview

Science.gov (United States)

Vulto, Arnold G.; Huys, Isabelle; Dylst, Pieter; Godman, Brian; Keuerleber, Simon; Claus, Barbara; Dimitrova, Maria; Petrova, Guenka; Sović-Brkičić, Ljiljana; Slabý, Juraj; Šebesta, Robin; Laius, Ott; Karr, Allan; Beck, Morgane; Martikainen, Jaana E.; Selke, Gisbert W.; Spillane, Susan; McCullagh, Laura; Trifirò, Gianluca; Vella Bonanno, Patricia; Mack, Asbjørn; Fogele, Antra; Viksna, Anita; Władysiuk, Magdalena; Mota-Filipe, Helder; Meshkov, Dmitry; Kalaba, Marija; Mencej Bedrač, Simona; Fürst, Jurij; Zara, Corrine; Skiöld, Peter; Magnússon, Einar; Simoens, Steven

2017-01-01

Background Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. Objectives The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. Methods An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. Results In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. Conclusions Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians

Policies for biosimilar uptake in Europe: An overview.

Directory of Open Access Journals (Sweden)

Evelien Moorkens

Full Text Available Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe.The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake.An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake.In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution.Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment

Absorption of Manganese and Iron in a Mouse Model of Hemochromatosis

Science.gov (United States)

Kim, Jonghan; Buckett, Peter D.; Wessling-Resnick, Marianne

2013-01-01

Hereditary hemochromatosis, an iron overload disease associated with excessive intestinal iron absorption, is commonly caused by loss of HFE gene function. Both iron and manganese absorption are regulated by iron status, but the relationships between the transport pathways of these metals and how they are affected by HFE-associated hemochromatosis remain poorly understood. Loss of HFE function is known to alter the intestinal expression of DMT1 (divalent metal transporter-1) and Fpn (ferroportin), transporters that have been implicated in absorption of both iron and manganese. Although the influence of HFE deficiency on dietary iron absorption has been characterized, potential effects on manganese metabolism have yet to be explored. To investigate the role of HFE in manganese absorption, we characterized the uptake and distribution of the metal in Hfe −/− knockout mice after intravenous, intragastric, and intranasal administration of 54Mn. These values were compared to intravenous and intragastric administration of 59Fe. Intestinal absorption of 59Fe was increased and clearance of injected 59Fe was also increased in Hfe−/− mice compared to controls. Hfe −/− mice displayed greater intestinal absorption of 54Mn compared to wild-type Hfe+/+ control mice. After intravenous injection, the distribution of 59Fe to heart and liver was greater in Hfe −/− mice but no remarkable differences were observed for 54Mn. Although olfactory absorption of 54Mn into blood was unchanged in Hfe −/− mice, higher levels of intranasally-instilled 54Mn were associated with Hfe−/− brain compared to controls. These results show that manganese transport and metabolism can be modified by HFE deficiency. PMID:23705020

Performance of a Zerovalent Iron Reactive Barrier for the Treatment of Arsenic in Groundwater: Part 2. Geochemical Modeling and Solid Phase Studies

Science.gov (United States)

Arsenic uptake processes were evaluated in a zerovalent iron reactive barrier installed at a lead smelting facility using geochemical modeling, solid-phase analysis, and X-ray absorption spectroscopy techniques. Aqueous speciation of arsenic plays a key role in directing arsenic...

Harry Potter and the sorcerer's scope: latent scope biases in explanatory reasoning.

Science.gov (United States)

Khemlani, Sangeet S; Sussman, Abigail B; Oppenheimer, Daniel M

2011-04-01

What makes a good explanation? We examine the function of latent scope, i.e., the number of unobserved phenomena that an explanation can account for. We show that individuals prefer narrow latent scope explanations-those that account for fewer unobserved effects-to broader explanations. In Experiments 1a-d, participants found narrow latent scope explanations to be both more satisfying and more likely. In Experiment 2 we directly manipulated base rate information and again found a preference for narrow latent scope explanations. Participants in Experiment 3 evaluated more natural explanations of unexpected observations, and again displayed a bias for narrow latent scope explanations. We conclude by considering what this novel bias tells us about how humans evaluate explanations and engage in causal reasoning.

Chemistry and the iron - only hydrogenase

International Nuclear Information System (INIS)

Tard, C.; Razavet, M.; Liu, X.; Ibrahim, S.; Pickett, Ch.

2005-01-01

Complete text of publication follows: Chemistry related to the hydrogenases is developing very rapidly and providing some informative insights into how the biological systems might function. Although still very much at a blue skies stage, there is some prospect for the design of artificial assemblies, materials and devices with technological application for hydrogen production/uptake provided robust system can be designed with low over potentials for hydrogen/proton interconversion (1). The iron-only hydrogenase possesses a peculiar di-iron unit coordinated by CO and CN, ligands which are normally associated with poisoning biological function. This sub-site unit is attached to a [4Fe4S] cubane center to form the catalytic site of the hydrogenase which is known as the 'H-cluster'. The synthesis of artificial sub-sites will first be described together with how their structures, spectroscopy and reactivity provides some key insights into the natural system viz. unprecedented bridging carbonyl and Fe(I) motifs in biology (2-4). How we have approached putting together the entire iron-sulfur framework of the H-cluster will then be described together with its electron-transfer and electrocatalytic properties (4). Finally, I will describe some early work on how we are beginning to incorporate structural motifs of the active-site into conducting polymer matrices, how they function as (albeit poor) electrocatalysts for hydrogen evolution, and where we see the way ahead. (1)The Chemistry and the Hydrogenases. D.J. Evans and C.J. Pickett, Chem. Soc. Rev., 32, 268-275, 2003; (2)Electron-Transfer at a Di-thiolate-Bridged Di-Iron Assembly; Electrocatalytic Hydrogen Evolution. S.J. Borg, T. Behrsing and S.P. Best, M. Ravazet, X. Liu and C.J. Pickett, J Amer. Chem. Soc., 2004, 126, 509-533; (3) Dissecting the intimate mechanism of cyanation of [Fe2S3] complexes related to the active site of all-iron hydrogenases by DFT analysis of energetics, transition states, intermediates and