Hepcidin Protects Neuron from Hemin-Mediated Injury by Reducing Iron

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Yu-Fu Zhou

2017-05-01

Full Text Available Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons. We conclude that hepcidin protects neuron from hemin-mediated injury by reducing iron via inhibition of expression of iron transport proteins.

Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

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Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

2015-09-01

Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably

Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.

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Robert Staroń

Full Text Available Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream.

The effect of psychological stress on iron absorption in rats

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Zhao Min

2009-11-01

Full Text Available Abstract Background Psychological stress (PS is recognized as an important pathogenic factor which leads to metabolism disorder in many diseases. Previous studies have shown that systemic iron homeostasis in mammalians was changed under specific stress conditions. Methods In present study, we used communication box to create psychological stress model and investigated the iron apparent absorption, iron accumulation in the apical poles of villous enterocytes and protein expressions of ferroportin 1 (FPN1, ferritin, divalent metal transporter 1 (DMT1. Results Our study showed that iron apparent absorption decreased and iron significantly accumulated in the apical poles of villous enterocytes in 3 d and 7 d PS groups. The expression of intestinal FPN1 in 3 d and 7 d PS groups was lower than that of control, while the change of intestinal ferritin was opposite. However, the expression of DMT1 did not change. Conclusion These results demonstrate that PS can decrease iron absorption in rats, which might be related to regulation expression of iron transporters.

Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

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Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

2012-01-01

Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

Current understanding of iron homeostasis.

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Anderson, Gregory J; Frazer, David M

2017-12-01

Iron is an essential trace element, but it is also toxic in excess, and thus mammals have developed elegant mechanisms for keeping both cellular and whole-body iron concentrations within the optimal physiologic range. In the diet, iron is either sequestered within heme or in various nonheme forms. Although the absorption of heme iron is poorly understood, nonheme iron is transported across the apical membrane of the intestinal enterocyte by divalent metal-ion transporter 1 (DMT1) and is exported into the circulation via ferroportin 1 (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around the body to sites of utilization with the erythroid marrow having particularly high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1 on the surface of most body cells, and after endocytosis of the complex, iron enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used for metabolic functions, stored within cytosolic ferritin, or exported from the cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption and iron export from the tissues into the plasma are regulated by the liver-derived peptide hepcidin. When tissue iron demands are high, hepcidin concentrations are low and vice versa. Too little or too much iron can have important clinical consequences. Most iron deficiency reflects an inadequate supply of iron in the diet, whereas iron excess is usually associated with hereditary disorders. These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload. Despite major recent advances, much remains to be learned about iron physiology and pathophysiology. © 2017 American Society for Nutrition.

Cellular iron transport.

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Garrick, Michael D; Garrick, Laura M

2009-05-01

Iron has a split personality as an essential nutrient that also has the potential to generate reactive oxygen species. We discuss how different cell types within specific tissues manage this schizophrenia. The emphasis in enterocytes is on regulating the body's supply of iron by regulating transport into the blood stream. In developing red blood cells, adaptations in transport manage the body's highest flux of iron. Hepatocytes buffer the body's stock of iron. Macrophage recycle the iron from effete red cells among other iron management tasks. Pneumocytes provide a barrier to prevent illicit entry that, when at risk of breaching, leads to a need to handle the dangers in a fashion essentially shared with macrophage. We also discuss or introduce cell types including renal cells, neurons, other brain cells, and more where our ignorance, currently still vast, needs to be removed by future research.

Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice

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Matak, Pavle; Zumerle, Sara; Mastrogiannaki, Maria; El Balkhi, Souleiman; Delga, Stephanie; Mathieu, Jacques R. R.; Canonne-Hergaux, François; Poupon, Joel; Sharp, Paul A.; Vaulont, Sophie; Peyssonnaux, Carole

2013-01-01

Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes. How systemic copper status regulates iron absorption is unknown. Mice were subjected to a nutritional copper deficiency-induced anemia regime from birth and injected with copper sulphate intraperitoneally to correct the anemia. Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia inducible factor 2α (HIF-2α) levels, a regulator of iron absorption. HIF-2α upregulation in copper deficiency appeared to be independent of duodenal iron or copper levels and correlated with the expression of iron transporters (Ferroportin - Fpn, Divalent Metal transporter – Dmt1) and ferric reductase – Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper injection resulted in down regulation of HIF-2α-regulated iron absorption genes in the gut. Our work identifies HIF-2α as an important regulator of iron transport machinery in copper deficiency. PMID:23555700

Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

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Desirrê Morais Dias

2015-11-01

Full Text Available Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7: Pontal bean (PB; rice + Pontal bean (R + BP; Pontal bean + sweet potato (PB + SP; Pontal bean + pumpkin (PB + P; Pontal bean + rice + sweet potato (PB + R + P; Pontal bean + rice + sweet potato (PB + R + SP; positive control (Ferrous Sulfate. The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE, gene expression of divalente metal transporter 1 (DMT-1, duodenal citocromo B (DcytB, ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC. The test groups, except the PB, showed higher HRE (p < 0.05 than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05 in the groups fed with high content carotenoid crops (sweet potato or pumpkin. The PB group presented lower (p < 0.05 TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity.

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

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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.

Understanding the management of iron deficiency anaemia

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impact on cellular respiration and ATP production, which in turn, decreases DNA ... by stimulating the degradation of ferroportin, the protein responsible for the ... to respond to oral iron therapy after 4 to 6 weeks (an increase of less than 1 g ...

Suppression of iron-regulatory hepcidin by vitamin D.

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Bacchetta, Justine; Zaritsky, Joshua J; Sea, Jessica L; Chun, Rene F; Lisse, Thomas S; Zavala, Kathryn; Nayak, Anjali; Wesseling-Perry, Katherine; Westerman, Mark; Hollis, Bruce W; Salusky, Isidro B; Hewison, Martin

2014-03-01

The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD.

Computational modeling and analysis of iron release from macrophages.

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Alka A Potdar

2014-07-01

Full Text Available A major process of iron homeostasis in whole-body iron metabolism is the release of iron from the macrophages of the reticuloendothelial system. Macrophages recognize and phagocytose senescent or damaged erythrocytes. Then, they process the heme iron, which is returned to the circulation for reutilization by red blood cell precursors during erythropoiesis. The amount of iron released, compared to the amount shunted for storage as ferritin, is greater during iron deficiency. A currently accepted model of iron release assumes a passive-gradient with free diffusion of intracellular labile iron (Fe2+ through ferroportin (FPN, the transporter on the plasma membrane. Outside the cell, a multi-copper ferroxidase, ceruloplasmin (Cp, oxidizes ferrous to ferric ion. Apo-transferrin (Tf, the primary carrier of soluble iron in the plasma, binds ferric ion to form mono-ferric and di-ferric transferrin. According to the passive-gradient model, the removal of ferrous ion from the site of release sustains the gradient that maintains the iron release. Subcellular localization of FPN, however, indicates that the role of FPN may be more complex. By experiments and mathematical modeling, we have investigated the detailed mechanism of iron release from macrophages focusing on the roles of the Cp, FPN and apo-Tf. The passive-gradient model is quantitatively analyzed using a mathematical model for the first time. A comparison of experimental data with model simulations shows that the passive-gradient model cannot explain macrophage iron release. However, a facilitated-transport model associated with FPN can explain the iron release mechanism. According to the facilitated-transport model, intracellular FPN carries labile iron to the macrophage membrane. Extracellular Cp accelerates the oxidation of ferrous ion bound to FPN. Apo-Tf in the extracellular environment binds to the oxidized ferrous ion, completing the release process. Facilitated-transport model can

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

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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

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.

Absorption of manganese and iron in a mouse model of hemochromatosis.

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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.

Fasting up-regulates ferroportin 1 expression via a Ghrelin/GHSR/MAPK signaling pathway.

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Luo, Qian-Qian; Zhou, Yu-Fu; Chen, Mesona Yung-Jin; Liu, Li; Ma, Juan; Zhang, Meng-Wan; Zhang, Fa-Li; Ke, Ya; Qian, Zhong-Ming

2018-01-01

The significant positive correlation between ghrelin and iron and hepcidin levels in the plasma of children with iron deficiency anemia prompted us to hypothesize that ghrelin may affect iron metabolism. Here, we investigated the effects of fasting or ghrelin on the expression of hepcidin, ferroportin 1 (Fpn1), transferrin receptor 1 (TfR1), ferritin light chain (Ft-L) proteins, and ghrelin, and also hormone secretagogue receptor 1 alpha (GHSR1α) and ghrelin O-acyltransferase (GOAT) mRNAs in the spleen and/or macrophage. We demonstrated that fasting induces a significant increase in the expression of ghrelin, GHSR1α, GOAT, and hepcidin mRNAs, as well as Ft-L and Fpn1 but not TfR1 proteins in the spleens of mice in vivo. Similar to the effects of fasting on the spleen, ghrelin induced a significant increase in the expression of Ft-L and Fpn1 but not TfR1 proteins in macrophages in vitro. In addition, ghrelin was found to induce a significant enhancement in phosphorylation of ERK as well as translocation of pERK from the cytosol to nuclei. Furthermore, the increased pERK and Fpn1 induced by ghrelin was demonstrated to be preventable by pre-treatment with either GHSR1α antagonist or pERK inhibitor. Our findings support the hypothesis that fasting upregulates Fpn1 expression, probably via a ghrelin/GHSR/MAPK signaling pathway. © 2017 Wiley Periodicals, Inc.

Absorption of Manganese and Iron in a Mouse Model of Hemochromatosis

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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

Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo.

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Soe-Lin, Shan; Apte, Sameer S; Andriopoulos, Billy; Andrews, Marc C; Schranzhofer, Matthias; Kahawita, Tanya; Garcia-Santos, Daniel; Ponka, Prem

2009-04-07

Natural resistance-associated macrophage protein 1 (Nramp1) is a divalent metal transporter expressed exclusively in phagocytic cells. We hypothesized that macrophage Nramp1 may participate in the recycling of iron acquired from phagocytosed senescent erythrocytes. To evaluate the role of Nramp1 in vivo, the iron parameters of WT and KO mice were analyzed after acute and chronic induction of hemolytic anemia. We found that untreated KO mice exhibited greater serum transferrin saturation and splenic iron content with higher duodenal ferroportin (Fpn) and divalent metal transporter 1 (DMT1) expression. Furthermore, hepatocyte iron content and hepcidin mRNA levels were dramatically lower in KO mice, indicating that hepcidin levels can be regulated by low-hepatocyte iron stores despite increased transferrin saturation. After acute treatment with the hemolytic agent phenylhydrazine (Phz), KO mice experienced a significant decrease in transferrin saturation and hematocrit, whereas WT mice were relatively unaffected. After a month-long Phz regimen, KO mice retained markedly increased quantities of iron within the liver and spleen and exhibited more pronounced splenomegaly and reticulocytosis than WT mice. After injection of (59)Fe-labeled heat-damaged reticulocytes, KO animals accumulated erythrophagocytosed (59)Fe within their liver and spleen, whereas WT animals efficiently recycled phagocytosed (59)Fe to the marrow and erythrocytes. These data imply that without Nramp1, iron accumulates within the liver and spleen during erythrophagocytosis and hemolytic anemia, supporting our hypothesis that Nramp1 promotes efficient hemoglobin iron recycling in macrophages. Our observations suggest that mutations in Nramp1 could result in a novel form of human hereditary iron overload.

TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease.

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Zhabyeyev, Pavel; Das, Subhash K; Basu, Ratnadeep; Shen, Mengcheng; Patel, Vaibhav B; Kassiri, Zamaneh; Oudit, Gavin Y

2018-05-01

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3 -/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3 -/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3 -/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key

Mitochondrial Iron Transport and Homeostasis in Plants

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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.

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

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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.

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

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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 Handling in Tumor-Associated Macrophages—Is There a New Role for Lipocalin-2?

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Michaela Jung

2017-09-01

Full Text Available Carcinogenesis is a multistep process. Besides somatic mutations in tumor cells, stroma-associated immunity is a major regulator of tumor growth. Tumor cells produce and secrete diverse mediators to create a local microenvironment that supports their own survival and growth. It is becoming apparent that iron acquisition, storage, and release in tumor cells is different from healthy counterparts. It is also appreciated that macrophages in the tumor microenvironment acquire a tumor-supportive, anti-inflammatory phenotype that promotes tumor cell proliferation, angiogenesis, and metastasis. Apparently, this behavior is attributed, at least in part, to the ability of macrophages to support tumor cells with iron. Polarization of macrophages by apoptotic tumor cells shifts the profile of genes involved in iron metabolism from an iron sequestering to an iron-release phenotype. Iron release from macrophages is supposed to be facilitated by ferroportin. However, lipid mediators such as sphingosine-1-phosphate, released form apoptotic tumor cells, upregulate lipocalin-2 (Lcn-2 in macrophages. This protein is known to bind siderophore-complexed iron and thus, may participate in iron transport in the tumor microenvironment. We describe how macrophages handle iron in the tumor microenvironment, discuss the relevance of an iron-release macrophage phenotype for tumor progression, and propose a new role for Lcn-2 in tumor-associated macrophages.

Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cycle arrest in MCF-7 cells.

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Bajbouj, Khuloud; Shafarin, Jasmin; Abdalla, Maher Y; Ahmad, Iman M; Hamad, Mawieh

2017-10-01

It is well established that several forms of cancer associate with significant iron overload. Recent studies have suggested that estrogen (E2) disrupts intracellular iron homeostasis by reducing hepcidin synthesis and maintaining ferroportin integrity. Here, the ability of E2 to alter intracellular iron status and cell growth potential was investigated in MCF-7 cells treated with increasing concentrations of E2. Treated cells were assessed for intracellular iron status, the expression of key proteins involved in iron metabolism, oxidative stress, cell survival, growth, and apoptosis. E2 treatment resulted in a significant reduction in hepcidin expression and a significant increase in hypoxia-inducible factor 1 alpha, ferroportin, transferrin receptor, and ferritin expression; a transient decrease in labile iron pool; and a significant increase in total intracellular iron content mainly at 20 nM/48 h E2 dose. Treated cells also showed increased total glutathione and oxidized glutathione levels, increased superoxide dismutase activity, and increased hemoxygenase 1 expression. Treatment with E2 at 20 nM for 48 h resulted in a significant reduction in cell growth (0.35/1 migration rate) and decreased cell survival (iron metabolism and precipitates adverse effects concerning cell viability, membrane integrity, and growth potential.

Rice and Bean Targets for Biofortification Combined with High Carotenoid Content Crops Regulate Transcriptional Mechanisms Increasing Iron Bioavailability

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Dias, Desirrê Morais; de Castro Moreira, Maria Eliza; Gomes, Mariana Juste Contin; Lopes Toledo, Renata Celi; Nutti, Marilia Regini; Pinheiro Sant’Ana, Helena Maria; Martino, Hércia Stampini Duarte

2015-01-01

Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p bioavailability and antioxidant capacity. PMID:26610564

NCOA4 Deficiency Impairs Systemic Iron Homeostasis

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Roberto Bellelli

2016-01-01

Full Text Available The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2–3 mg/kg, mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg, mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239–614 restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

Heme metabolism as an integral part of iron homeostasis

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Paweł Lipiński

2014-01-01

Full Text Available Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways – heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S] – is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

[Heme metabolism as an integral part of iron homeostasis].

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Lipiński, Paweł; Starzyński, Rafał R; Styś, Agnieszka; Gajowiak, Anna; Staroń, Robert

2014-01-02

Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways--heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S])--is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis) as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages.

Modern iron replacement therapy: clinical and pathophysiological insights.

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Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

2018-01-01

Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

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

Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

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Chen, Qian; Xiao, De-Sheng

2014-01-30

Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

Basic mechanisms of iron metabolism regulation and their clinical significance

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L. M. Meshсheryakova

2014-01-01

Full Text Available This article is а composition of literature and experimental data of iron metabolism. There were studied the level of DMT-1, ferroportin, hepcidin at different stages of anemia and hemochromatosis. It is clear that the level of DMT-1 regulates by the hepcidin. Increaseing of the hepcidin concentration and decreasing DMT-1 level in patients with hemochromatosis explained good results of treatment.

Basic mechanisms of iron metabolism regulation and their clinical significance

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L. M. Meshсheryakova

2015-01-01

Full Text Available This article is а composition of literature and experimental data of iron metabolism. There were studied the level of DMT-1, ferroportin, hepcidin at different stages of anemia and hemochromatosis. It is clear that the level of DMT-1 regulates by the hepcidin. Increaseing of the hepcidin concentration and decreasing DMT-1 level in patients with hemochromatosis explained good results of treatment.

Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis

Czech Academy of Sciences Publication Activity Database

Balounová, Jana; Vavrochová, Tereza; Benešová, Martina; Ballek, Ondřej; Kolář, Michal; Filipp, Dominik

2014-01-01

Roč. 44, č. 5 (2014), s. 1491-1502 ISSN 0014-2980 R&D Projects: GA AV ČR IAA500520707 Institutional support: RVO:68378050 Keywords : Embryo nic macrophages * Ferroportin * Gene expression microarray * Iron metabolism * TLR stimulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.034, year: 2014

Toll- like receptors expressed on embryonic macrophages couple inflammatory signals to iron metabolism during early ontogenesis

Czech Academy of Sciences Publication Activity Database

Balounová, Jana; Vavrochová, Tereza; Benešová, Martina; Ballek, Ondřej; Kolář, Michal; Filipp, Dominik

2014-01-01

Roč. 44, č. 5 (2014), s. 1491-1502 ISSN 0014-2980 R&D Projects: GA AV ČR IAA500520707 Institutional support: RVO:68378050 Keywords : Embryonic macrophages * Ferroportin * Gene expression microarray * Iron metabolism * TLR stimulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.034, year: 2014

Hemolytic anemia repressed hepcidin level without hepatocyte iron overload: lesson from Günther disease model.

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Millot, Sarah; Delaby, Constance; Moulouel, Boualem; Lefebvre, Thibaud; Pilard, Nathalie; Ducrot, Nicolas; Ged, Cécile; Lettéron, Philippe; de Franceschi, Lucia; Deybach, Jean Charles; Beaumont, Carole; Gouya, Laurent; De Verneuil, Hubert; Lyoumi, Saïd; Puy, Hervé; Karim, Zoubida

2017-02-01

Hemolysis occurring in hematologic diseases is often associated with an iron loading anemia. This iron overload is the result of a massive outflow of hemoglobin into the bloodstream, but the mechanism of hemoglobin handling has not been fully elucidated. Here, in a congenital erythropoietic porphyria mouse model, we evaluate the impact of hemolysis and regenerative anemia on hepcidin synthesis and iron metabolism. Hemolysis was confirmed by a complete drop in haptoglobin, hemopexin and increased plasma lactate dehydrogenase, an increased red blood cell distribution width and osmotic fragility, a reduced half-life of red blood cells, and increased expression of heme oxygenase 1. The erythropoiesis-induced Fam132b was increased, hepcidin mRNA repressed, and transepithelial iron transport in isolated duodenal loops increased. Iron was mostly accumulated in liver and spleen macrophages but transferrin saturation remained within the normal range. The expression levels of hemoglobin-haptoglobin receptor CD163 and hemopexin receptor CD91 were drastically reduced in both liver and spleen, resulting in heme- and hemoglobin-derived iron elimination in urine. In the kidney, the megalin/cubilin endocytic complex, heme oxygenase 1 and the iron exporter ferroportin were induced, which is reminiscent of significant renal handling of hemoglobin-derived iron. Our results highlight ironbound hemoglobin urinary clearance mechanism and strongly suggest that, in addition to the sequestration of iron in macrophages, kidney may play a major role in protecting hepatocytes from iron overload in chronic hemolysis. Copyright© Ferrata Storti Foundation.

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

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

Enterobactin-mediated iron transport in Pseudomonas aeruginosa.

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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

The iron-chelate transporter OsYSL9 plays a role in iron distribution in developing rice grains.

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Senoura, Takeshi; Sakashita, Emi; Kobayashi, Takanori; Takahashi, Michiko; Aung, May Sann; Masuda, Hiroshi; Nakanishi, Hiromi; Nishizawa, Naoko K

2017-11-01

Rice OsYSL9 is a novel transporter for Fe(II)-nicotianamine and Fe(III)-deoxymugineic acid that is responsible for internal iron transport, especially from endosperm to embryo in developing seeds. Metal chelators are essential for safe and efficient metal translocation in plants. Graminaceous plants utilize specific ferric iron chelators, mugineic acid family phytosiderophores, to take up sparingly soluble iron from the soil. Yellow Stripe 1-Like (YSL) family transporters are responsible for transport of metal-phytosiderophores and structurally similar metal-nicotianamine complexes. Among the rice YSL family members (OsYSL) whose functions have not yet been clarified, OsYSL9 belongs to an uncharacterized subgroup containing highly conserved homologs in graminaceous species. In the present report, we showed that OsYSL9 localizes mainly to the plasma membrane and transports both iron(II)-nicotianamine and iron(III)-deoxymugineic acid into the cell. Expression of OsYSL9 was induced in the roots but repressed in the nonjuvenile leaves in response to iron deficiency. In iron-deficient roots, OsYSL9 was induced in the vascular cylinder but not in epidermal cells. Although OsYSL9-knockdown plants did not show a growth defect under iron-sufficient conditions, these plants were more sensitive to iron deficiency in the nonjuvenile stage compared with non-transgenic plants. At the grain-filling stage, OsYSL9 expression was strongly and transiently induced in the scutellum of the embryo and in endosperm cells surrounding the embryo. The iron concentration was decreased in embryos of OsYSL9-knockdown plants but was increased in residual parts of brown seeds. These results suggested that OsYSL9 is involved in iron translocation within plant parts and particularly iron translocation from endosperm to embryo in developing seeds.

Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

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Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

2014-02-01

Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

Obesity as an Emerging Risk Factor for Iron Deficiency

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Elmar Aigner

2014-09-01

Full Text Available Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS or nonalcoholic fatty liver disease (NAFLD. This constellation has been named the “dysmetabolic iron overload syndrome (DIOS”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

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Shuangying Hao

2016-03-01

Full Text Available Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI following subarachnoid hemorrhage (SAH. This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Calcium channel blockers ameliorate iron overload-associated hepatic fibrosis by altering iron transport and stellate cell apoptosis

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Department of Pathology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang 050200, Hebei (China); Zhao, Xin [Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei (China); Chang, Yanzhong [Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei (China); Zhang, Yuanyuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Xi [Department of Pharmacy, The Forth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei (China); Zhang, Xuan [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Liu, Zhenyi; Guo, Hui [Department of Medicinal Chemistry, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Wang, Na [Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Gao, Yonggang [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Zhang, Jianping, E-mail: zhangjianping14@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Chu, Li, E-mail: chuli0614@126.com [Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei (China); Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei (China)

2016-06-15

Liver fibrosis is the principal cause of morbidity and mortality in patients with iron overload. Calcium channel blockers (CCBs) can antagonize divalent cation entry into renal and myocardial cells and inhibit fibrogenic gene expression. We investigated the potential of CCBs to resolve iron overload-associated hepatic fibrosis. Kunming mice were assigned to nine groups (n = 8 per group): control, iron overload, deferoxamine, high and low dose verapamil, high and low dose nimodipine, and high and low dose diltiazem. Iron deposition and hepatic fibrosis were measured in mouse livers. Expression levels of molecules associated with transmembrane iron transport were determined by molecular biology approaches. In vitro HSC-T6 cells were randomized into nine groups (the same groups as the mice). Changes in proliferation, apoptosis, and metalloproteinase expression in cells were detected to assess the anti-fibrotic effects of CCBs during iron overload conditions. We found that CCBs reduced hepatic iron content, intracellular iron deposition, the number of hepatic fibrotic areas, collagen expression levels, and hydroxyproline content. CCBs rescued abnormal expression of α1C protein in L-type voltage-dependent calcium channel (LVDCC) and down-regulated divalent metal transporter-1 (DMT-1) expression in mouse livers. In iron-overloaded HSC-T6 cells, CCBs reduced iron deposition, inhibited proliferation, induced apoptosis, and elevated expression of matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). CCBs are potential therapeutic agents that can be used to address hepatic fibrosis during iron overload. They resolve hepatic fibrosis probably correlated with regulating transmembrane iron transport and inhibiting HSC growth. - Highlights: • Calcium channel blockers (CCBs) reduced hepatic iron content. • CCBs decreased hepatic fibrotic areas and collagen expression levels. • CCBs resolve fibrosis by regulating iron transport and

Evaluation of iron transport from ferrous glycinate liposomes using ...

African Journals Online (AJOL)

Background: Iron fortification of foods is currently a strategy employed to fight iron deficiency in countries. Liposomes were assumed to be a potential carrier of iron supplements. Objective: The objective of this study was to investigate the iron transport from ferrous glycinate liposomes, and to estimate the effects of liposomal ...

Vacuolar iron transporter BnMEB2 is involved in enhancing iron tolerance of Brassica napus

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Wei Zhu

2016-09-01

Full Text Available Iron toxicity is a major nutrient disorder that severely affects crop development and yield. Vacuolar detoxification of metal stress is an important strategy for plants to survive and adapt to this adverse environment. Vacuolar iron transporter (VIT members are involved in this process and play essential roles in iron storage and transport. In this study, a rapeseed VIT gene BnMEB2 (BnaC07g30170D was identified. BnMEB2 is a homolog to Arabidopsis MEB2 (At5g24290 and acts as a detoxifier in vacuolar sequestration of divalent metal. Transient expression analysis revealed that BnMEB2 was localized to the vacuolar membrane. Q-PCR detection showed a high expression of BnMEB2 in mature (60-day-old leaves and could be obviously induced by exogenous iron stress in both roots and leaves. Over-expressed BnMEB2 in both Arabidopsis wild type and meb2 mutant seedlings resulted in greatly improved iron tolerability with no significant changes in the expression level of other vacuolar iron transporter genes. The mutant meb2 grew slowly and its root hair elongation was inhibited under high iron concentration condition while BnMEB2 over-expressed transgenic plants of the mutant restored the phenotypes with apparently higher iron storage in roots and dramatically increased iron content in the whole plant. Taken together, these results suggested that BnMEB2 was a VIT gene in rapeseed which was necessary for safe storage and vacuole detoxification function of excess iron to enhance the tolerance of iron toxicity. This research sheds light on a potentially new strategy for attenuating hazardous metal stress from environment and improving iron biofortification in Brassicaceae crops.

Solid-state Water-mediated Transport Reduction of Nanostructured Iron Oxides

International Nuclear Information System (INIS)

Smirnov, Vladimir M.; Povarov, Vladimir G.; Voronkov, Gennadii P.; Semenov, Valentin G.; Murin, Igor' V.; Gittsovich, Viktor N.; Sinel'nikov, Boris M.

2001-01-01

The Fe 2+ /Fe 3+ ratio in two-dimensional iron oxide nanosructures (nanolayers with a thickness of 0.3-1.5 nm on silica surface) may be precisely controlled using the transport reduction (TR) technique. The species ≡-O-Fe(OH) 2 and (≡Si-O-) 2 -FeOH forming the surface monolayer are not reduced at 400-600 deg. C because of their covalent bonding to the silica surface, as demonstrated by Moessbauer spectroscopy. Iron oxide microparticles (microstructures) obtained by the impregnation technique, being chemically unbound to silica, are subjected to reduction at T ≥ 500 deg. C with formation of metallic iron in the form of α-Fe. Transport reduction of supported nanostructures (consisting of 1 or 4 monolayers) at T ≥ 600 deg. C produces bulk iron(II) silicate and metallic iron phases. The structural-chemical transformations occurring in transport reduction of supported iron oxide nanolayers are proved to be governed by specific phase processes in the nanostructures themselves

Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

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Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

2008-02-22

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

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Qi Xu

2016-01-01

Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells.

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McCarthy, Ryan C; Kosman, Daniel J

2014-01-01

We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a cell-derived barrier. We found that iron efflux from hBMVEC through the ferrous iron permease ferroportin (Fpn) was stimulated by secretion of the soluble form of the multi-copper ferroxidase, ceruloplasmin (sCp) from the co-cultured C6 cells. Reciprocally, expression of sCp mRNA in the C6 cells was increased by neighboring hBMVEC. In addition, data indicate that C6 cell-secreted hepcidin stimulates internalization of hBMVEC Fpn but only when the end-feet projections characteristic of this glia-derived cell line are proximal to the endothelial cells. This hepcidin-dependent loss of Fpn correlated with knock-down of iron efflux from the hBMVEC; this result was consistent with the mechanism by which hepcidin regulates iron efflux in mammalian cells. In summary, the data support a model of iron trafficking across the BBB in which the capillary endothelium induce the underlying astrocytes to produce the ferroxidase activity needed to support Fpn-mediated iron efflux. Reciprocally, astrocyte proximity modulates the effective concentration of hepcidin at the endothelial cell membrane and thus the surface expression of hBMVEC Fpn. These results are independent of the source of hBMVEC iron (transferrin or non-transferrin bound) indicating that the model developed here is broadly applicable to brain iron homeostasis.

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

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

Iron addiction: a novel therapeutic target in ovarian cancer

International Nuclear Information System (INIS)

Basuli, D.

2017-01-01

Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependence on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Some mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). Here, we show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.

Iron transport and storage in the coccolithophore: Emiliania huxleyi.

Science.gov (United States)

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.

Iron overload patients with unknown etiology from national survey in Japan.

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Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

2017-03-01

Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

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

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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.

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

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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.

Change of iron species and iron solubility in Asian dust during the long-range transport from western China to Japan

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Y. Takahashi

2011-11-01

Full Text Available In the North Pacific, transport and deposition of mineral dust from Asia appear to be one of major sources of iron which can regulate growth of phytoplankton in the ocean. In this process, it is essential to identify chemical species of iron contained in Asian dust, because bioavailability of iron in the ocean is strongly influenced by the solubility of iron, which in turn is dependent on iron species in the dust. Here, we report that clay minerals (illite and chlorite in the dusts near the source collected at Aksu (western China can be transformed into ferrihydrite by atmospheric chemical processes during their long-range transport to eastern China (Qingdao and Japan (Tsukuba based on the speciation by X-ray absorption fine structure (XAFS and other methods such as X-ray diffraction and chemical extraction. As a result, Fe molar ratio in Aksu (illite : chlorite : ferrihydrite = 70 : 25 : 5 was changed to that in Tsukuba (illite : chlorite : ferrihydrite = 65 : 10 : 25. Moreover, leaching experiments were conducted to study the change of iron solubility. It was found that the iron solubility for the dust in Tsukuba (soluble iron fraction: 11.8 % and 1.10 % for synthetic rain water and seawater, respectively was larger than that in Aksu (4.1 % and 0.28 %, respectively, showing that iron in the dust after the transport becomes more soluble possibly due to the formation of ferrihydrite in the atmosphere. Our findings suggested that secondary formation of ferrihydrite during the transport should be considered as one of important processes in evaluating the supply of soluble iron to seawater.

High-Throughput Screening of Small Molecules Identifies Hepcidin Antagonists

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Fung, Eileen; Sugianto, Priscilla; Hsu, Jason; Damoiseaux, Robert; Ganz, Tomas

2013-01-01

Anemia of inflammation (AI) is common in patients with infection, autoimmune diseases, cancer, and chronic kidney disease. Unless the underlying condition can be reversed, treatment options are limited to erythropoiesis-stimulating agents with or without intravenous iron therapy, modalities that are not always effective and can cause serious adverse effects. Hepcidin, the iron regulatory hormone, has been identified as a pathogenic factor in the development of AI. To explore new therapeutic options for AI and other iron-related disorders caused by hepcidin excess, we developed a cell-based screen to identify hepcidin antagonists. Of the 70,000 small molecules in the library, we identified 14 compounds that antagonized the hepcidin effect on ferroportin. One of these was fursultiamine, a Food and Drug Administration (FDA)–approved thiamine derivative. Fursultiamine directly interfered with hepcidin binding to its receptor, ferroportin, by blocking ferroportin C326 thiol residue essential for hepcidin binding. Consequently, fursultiamine prevented hepcidin-induced ferroportin ubiquitination, endocytosis, and degradation in vitro and allowed continuous cellular iron export despite the presence of hepcidin, with IC50 in the submicromolar range. Thiamine, the fursultiamine metabolite, and benfotiamine, another thiamine derivative, did not interfere with the effect of hepcidin on ferroportin. Other FDA-approved thiol-reactive compounds were at least 1000-fold less potent than fursultiamine in antagonizing hepcidin. In vivo, fursultiamine did not reproducibly antagonize the effect of hepcidin on serum iron, likely because of its rapid conversion to inactive metabolites. Fursultiamine is a unique antagonist of hepcidin in vitro that could serve as a template for the development of drug candidates that inhibit the hepcidin-ferroportin interaction. PMID:23292796

Thickness Optimisation of Textiles Subjected to Heat and Mass Transport during Ironing

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Korycki Ryszard

2016-09-01

Full Text Available Let us next analyse the coupled problem during ironing of textiles, that is, the heat is transported with mass whereas the mass transport with heat is negligible. It is necessary to define both physical and mathematical models. Introducing two-phase system of mass sorption by fibres, the transport equations are introduced and accompanied by the set of boundary and initial conditions. Optimisation of material thickness during ironing is gradient oriented. The first-order sensitivity of an arbitrary objective functional is analysed and included in optimisation procedure. Numerical example is the thickness optimisation of different textile materials in ironing device.

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.

A vacuolar iron transporter in tulip, TgVit1, is responsible for blue coloration in petal cells through iron accumulation.

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Momonoi, Kazumi; Yoshida, Kumi; Mano, Shoji; Takahashi, Hideyuki; Nakamori, Chihiro; Shoji, Kazuaki; Nitta, Akira; Nishimura, Mikio

2009-08-01

Blue color in flowers is due mainly to anthocyanins, and a considerable part of blue coloration can be attributed to metal-complexed anthocyanins. However, the mechanism of metal ion transport into vacuoles and subsequent flower color development has yet to be fully explored. Previously, we studied the mechanism of blue color development specifically at the bottom of the inner perianth in purple tulip petals of Tulipa gesneriana cv. Murasakizuisho. We found that differences in iron content were associated with the development of blue- and purple-colored cells. Here, we identify a vacuolar iron transporter in T. gesneriana (TgVit1), and characterize the localization and function of this transporter protein in tulip petals. The amino acid sequence of TgVit1 is 85% similar that of the Arabidopsis thaliana vacuolar iron transporter AtVIT1, and also showed similarity to the AtVIT1 homolog in yeast, Ca(2+)-sensitive cross-complementer 1 (CCC1). The gene TgVit1 was expressed exclusively in blue-colored epidermal cells, and protein levels increased with increasing mRNA expression and blue coloration. Transient expression experiments revealed that TgVit1 localizes to the vacuolar membrane, and is responsible for the development of the blue color in purple cells. Expression of TgVit1 in yeast rescued the growth defect of ccc1 mutant cells in the presence of high concentrations of FeSO(4). Our results indicate that TgVit1 plays an essential role in blue coloration as a vacuolar iron transporter in tulip petals. These results suggest a new role for involvement of a vacuolar iron transporter in blue flower color development.

Hepcidin: an important iron metabolism regulator in chronic kidney disease

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Sandra Azevedo Antunes

Full Text Available Abstract Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population.

The ferrous iron transporter FtrABCD is required for the virulence of Brucella abortus 2308 in mice.

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Elhassanny, Ahmed E M; Anderson, Eric S; Menscher, Evan A; Roop, R Martin

2013-06-01

Iron transport has been linked to the virulence of Brucella strains in both natural and experimental hosts. The genes designated BAB2_0837-0840 in the Brucella abortus 2308 genome sequence are predicted to encode a CupII-type ferrous iron transporter homologous to the FtrABCD transporter recently described in Bordetella. To study the role of the Brucella FtrABCD in iron transport, an isogenic ftrA mutant was constructed from B. abortus 2308. Compared with the parental strain, the B. abortus ftrA mutant displays a decreased capacity to use non-haem iron sources in vitro, a growth defect in a low iron medium that is enhanced at pH 6, and studies employing radiolabelled FeCl3 confirmed that FtrABCD transports ferrous iron. Transcription of the ftrA gene is induced in B. abortus 2308 in response to iron deprivation and exposure to acid pH, and similar to other Brucella iron acquisition genes that have been examined the iron-responsiveness of ftrA is dependent upon the iron response regulator Irr. The B. abortus ftrA mutant exhibits significant attenuation in both cultured murine macrophages and experimentally infected mice, supporting the proposition that ferrous iron is a critical iron source for these bacteria in the mammalian host. © 2013 John Wiley & Sons Ltd.

Use of Electrophoresis for Transporting Nano-Iron in Porous Media

Science.gov (United States)

Research was conducted to evaluate if electrophoresis could transport surface stabilized nanoscale zero-valent iron (nZVI) through fine grained sand with the intent of remediating a contaminant in situ. The experimental procedure involved determining the transport rates of poly...

A solute-binding protein for iron transport in Streptococcus iniae

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Li Anxing

2010-12-01

Full Text Available Abstract Background Streptococcus iniae (S. iniae is a major pathogen that causes considerable morbidity and mortality in cultured fish worldwide. The pathogen's ability to adapt to the host affects the extent of infection, hence understanding the mechanisms by which S. iniae overcomes physiological stresses during infection will help to identify potential virulence determinants of streptococcal infection. Grow S. iniae under iron-restricted conditions is one approach for identifying host-specific protein expression. Iron plays an important role in many biological processes but it has low solubility under physiological condition. Many microorganisms have been shown to be able to circumvent this nutritional limitation by forming direct contacts with iron-containing proteins through ATP-binding cassette (ABC transporters. The ABC transporter superfamilies constitute many different systems that are widespread among living organisms with different functions, such as ligands translocation, mRNA translation, and DNA repair. Results An ABC transporter system, named as mtsABC (metal transport system was cloned from S. iniae HD-1, and was found to be involved in heme utilization. mtsABC is cotranscribed by three downstream genes, i.e., mtsA, mtsB, and mtsC. In this study, we cloned the first gene of the mtsABC transporter system (mtsA, and purified the corresponding recombinant protein MtsA. The analysis indicated that MtsA is a putative lipoprotein which binds to heme that can serve as an iron source for the microorganism, and is expressed in vivo during Kunming mice infection by S. iniae HD-1. Conclusions This is believed to be the first report on the cloning the ABC transporter lipoprotein from S. iniae genomic DNA. Together, our data suggested that MtsA is associated with heme, and is expressed in vivo during Kunming mice infection by S. iniae HD-1 which indicated that it can be a potential candidate for S. iniae subunit vaccine.

HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

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Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

2009-05-01

Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

Inflammation and ER Stress Downregulate BDH2 Expression and Dysregulate Intracellular Iron in Macrophages

Directory of Open Access Journals (Sweden)

Susu M. Zughaier

2014-01-01

Full Text Available Macrophages play a very important role in host defense and in iron homeostasis by engulfing senescent red blood cells and recycling iron. Hepcidin is the master iron regulating hormone that limits dietary iron absorption from the gut and limits iron egress from macrophages. Upon infection macrophages retain iron to limit its bioavailability which limits bacterial growth. Recently, a short chain butyrate dehydrogenase type 2 (BDH2 protein was reported to contain an iron responsive element and to mediate cellular iron trafficking by catalyzing the synthesis of the mammalian siderophore that binds labile iron; therefore, BDH2 plays a crucial role in intracellular iron homeostasis. However, BDH2 expression and regulation in macrophages have not yet been described. Here we show that LPS-induced inflammation combined with ER stress led to massive BDH2 downregulation, increased the expression of ER stress markers, upregulated hepcidin expression, downregulated ferroportin expression, caused iron retention in macrophages, and dysregulated cytokine release from macrophages. We also show that ER stress combined with inflammation synergistically upregulated the expression of the iron carrier protein NGAL and the stress-inducible heme degrading enzyme heme oxygenase-1 (HO-1 leading to iron liberation. This is the first report to show that inflammation and ER stress downregulate the expression of BDH2 in human THP-1 macrophages.

Draft ASME code case on ductile cast iron for transport packaging

International Nuclear Information System (INIS)

Saegusa, T.; Arai, T.; Hirose, M.; Kobayashi, T.; Tezuka, Y.; Urabe, N.; Hueggenberg, R.

2004-01-01

The current Rules for Construction of ''Containment Systems for Storage and Transport Packagings of Spent Nuclear Fuel and High Level Radioactive Material and Waste'' of Division 3 in Section III of ASME Code (2001 Edition) does not include ductile cast iron in its list of materials permitted for use. The Rules specify required fracture toughness values of ferritic steel material for nominal wall thickness 5/8 to 12 inches (16 to 305 mm). New rule for ductile cast iron for transport packaging of which wall thickness is greater than 12 inches (305mm) is required

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

Chloroplast Iron Transport Proteins - Function and Impact on Plant Physiology.

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López-Millán, Ana F; Duy, Daniela; Philippar, Katrin

2016-01-01

Chloroplasts originated about three billion years ago by endosymbiosis of an ancestor of today's cyanobacteria with a mitochondria-containing host cell. During evolution chloroplasts of higher plants established as the site for photosynthesis and thus became the basis for all life dependent on oxygen and carbohydrate supply. To fulfill this task, plastid organelles are loaded with the transition metals iron, copper, and manganese, which due to their redox properties are essential for photosynthetic electron transport. In consequence, chloroplasts for example represent the iron-richest system in plant cells. However, improvement of oxygenic photosynthesis in turn required adaptation of metal transport and homeostasis since metal-catalyzed generation of reactive oxygen species (ROS) causes oxidative damage. This is most acute in chloroplasts, where radicals and transition metals are side by side and ROS-production is a usual feature of photosynthetic electron transport. Thus, on the one hand when bound by proteins, chloroplast-intrinsic metals are a prerequisite for photoautotrophic life, but on the other hand become toxic when present in their highly reactive, radical generating, free ionic forms. In consequence, transport, storage and cofactor-assembly of metal ions in plastids have to be tightly controlled and are crucial throughout plant growth and development. In the recent years, proteins for iron transport have been isolated from chloroplast envelope membranes. Here, we discuss their putative functions and impact on cellular metal homeostasis as well as photosynthetic performance and plant metabolism. We further consider the potential of proteomic analyses to identify new players in the field.

Miraxanthin-V, Liriodenin and Chitranone are Hepcidin Antagonist In silico for Iron Deficiency Anemia

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Yotriana, S.; Suselo, YH; Muthmainah; Indarto, D.

2018-03-01

Anemia is one of the greatest nutrition problem in the world that is commonly found in children, pregnant women and reproductive women. This disorder is predominantly caused by iron deficiency. Hepcidin, a hepatic hormone, regulates iron metabolism and high serum levels of this hormone are detected in patients with iron deficiency anemia (IDA). Anticalin is a sintetic compound which is able to interacts with hepcidin leading to inhibition of ferroportin-hepcidin binding complexes but its therapeutic effects are still under investigation. Indonesia has various herbal plants which are potentially developed to treat some human diseases. Therefore, the purpose of this study was to identify phytochemicals derived from Indonesian plants that is able to inhibit hepcidin-ferroportin interaction. A bioinformatics study with molecular docking method was used in this study. Three-dimensional structures of human hepcidin and anticalin were obtained from the Protein Data Bank (ID: 1M4F and 4QAE respectively). Because their molecular size was big, each molecule was cut into 2 parts of its binding sites. All phytochemicals structures were obtained from HerbalDB and PubChem NCBI database. Truncated anticalin/phytochemicals were molecularly docked with truncated hepcidin by using AutoDock Vina 1.1.2. and their interactions were visualized using PyMol 1.3. Truncated Anticalin had -4.6 and -4.2 kcal/mol binding affinity to truncated human hepcidin. Truncated anticalin 1 was bound to Cys13, Cys14, Arg16 and Ser17 residues in truncated hepcidin 1 while truncated anticalin 2 was at Cy23 and Lys24 residues in truncated hepcidin 2. Miraxanthine-V, Liriodenin and Chitranone had lower binding affinity (-4.8±0.77, -4.7±0.33 and -5.01±0.30 kcal/mol respectively) than that of anticalin and occupied binding sites as same as anticalin did. There are three phytochemicals that potentially become hepcidin antagonists in silico. In vitro assays are required for verification of the antagonist

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

Geochemical investigation of iron transport into bentonite as steel corrodes

International Nuclear Information System (INIS)

Hunter, Fiona; Bate, Fiona; Heath, Tim; Hoch, Andrew

2007-09-01

some experiments. Using the experimental data as a guide, a modelling investigation has been carried out. The objectives of the modelling investigation were: To develop a geochemical model of the transport of iron into bentonite based on the clear experimental evidence of the penetration of iron into bentonite. To improve our understanding of the desaturation of the bentonite as water is consumed during the corrosion process and the resultant gas(es) escapes. The production of iron from the corroding source was modelled using a rate of gas evolution that had been fitted. It was shown that ion exchange and surface complexation processes do not provide sufficient sorption to predict the high amount of iron observed in the solid phase. Therefore alternative processes, such as iron-containing mineral formation or mineral transformations, were also suggested to account for the amount of iron observed within the bentonite phase. Magnetite was identified as the most thermodynamically stable solubility limiting phase under the experimental conditions. A one-dimensional transport model was constructed to include all relevant processes. The simulations considered the diffusive transport of Fe 2+ ions away from a corroding source, using the rate of gas evolution resulting from the corrosion process. Ion exchange and surface complexation processes were allowed within the bentonite which would provide sorption of iron onto and within the bentonite solid. The pH was buffered by allowing protonation and deprotonation of the surface sites of the bentonite solid. In addition, saturation of iron-containing minerals was permitted. The base case model suggests that about 4.4 wt % of iron could form in the bentonite if the formation of magnetite was allowed. However, the maximum theoretical amount of iron available from the source term is limited to 4.5 wt % of iron by the cumulative gas evolution rate, which is lower than the observed amount of iron in the bulk bentonite (6.6 wt %). A

Geochemical investigation of iron transport into bentonite as steel corrodes

Energy Technology Data Exchange (ETDEWEB)

Hunter, Fiona; Bate, Fiona; Heath, Tim; Hoch, Andrew [Serco Assurance, Harwe ll (United Kingdom)

2007-09-15

some experiments. Using the experimental data as a guide, a modelling investigation has been carried out. The objectives of the modelling investigation were: To develop a geochemical model of the transport of iron into bentonite based on the clear experimental evidence of the penetration of iron into bentonite. To improve our understanding of the desaturation of the bentonite as water is consumed during the corrosion process and the resultant gas(es) escapes. The production of iron from the corroding source was modelled using a rate of gas evolution that had been fitted. It was shown that ion exchange and surface complexation processes do not provide sufficient sorption to predict the high amount of iron observed in the solid phase. Therefore alternative processes, such as iron-containing mineral formation or mineral transformations, were also suggested to account for the amount of iron observed within the bentonite phase. Magnetite was identified as the most thermodynamically stable solubility limiting phase under the experimental conditions. A one-dimensional transport model was constructed to include all relevant processes. The simulations considered the diffusive transport of Fe{sup 2+} ions away from a corroding source, using the rate of gas evolution resulting from the corrosion process. Ion exchange and surface complexation processes were allowed within the bentonite which would provide sorption of iron onto and within the bentonite solid. The pH was buffered by allowing protonation and deprotonation of the surface sites of the bentonite solid. In addition, saturation of iron-containing minerals was permitted. The base case model suggests that about 4.4 wt % of iron could form in the bentonite if the formation of magnetite was allowed. However, the maximum theoretical amount of iron available from the source term is limited to 4.5 wt % of iron by the cumulative gas evolution rate, which is lower than the observed amount of iron in the bulk bentonite (6.6 wt

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

Science.gov (United States)

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.

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational De-repression of HIF2α

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Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Noguchi, Audrey; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Graham, Brian B.; Tuder, Rubin M.; Yu, Zu-Xi; Eckhaus, Michael; Lee, Jaekwon; Springer, Danielle A.; Rouault, Tracey A.

2013-01-01

SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. PMID:23395173

Local iron homeostasis in the breast ductal carcinoma microenvironment

International Nuclear Information System (INIS)

Marques, Oriana; Porto, Graça; Rêma, Alexandra; Faria, Fátima; Cruz Paula, Arnaud; Gomez-Lazaro, Maria; Silva, Paula; Martins da Silva, Berta; Lopes, Carlos

2016-01-01

While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. We confirm previous results by showing that breast cancer epithelial cells present an ‘iron-utilization phenotype’ with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an ‘iron-donor’ phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context

The actin-binding protein profilin 2 is a novel regulator of iron homeostasis.

Science.gov (United States)

Luscieti, Sara; Galy, Bruno; Gutierrez, Lucia; Reinke, Michael; Couso, Jorge; Shvartsman, Maya; Di Pascale, Antonio; Witke, Walter; Hentze, Matthias W; Pilo Boyl, Pietro; Sanchez, Mayka

2017-10-26

Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis -regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 ( Pfn2 ) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter release, as a novel IRP-interacting transcript, and studied its role in iron metabolism. A combination of electrophoretic mobility shift assay experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3' untranslated region of Pfn2 mRNA. Pfn2 mRNA levels were significantly reduced in duodenal samples from mice with intestinal IRP ablation, suggesting that IRPs exert a positive effect on Pfn2 mRNA expression in vivo. Overexpression of Pfn2 in HeLa and Hepa1-6 cells reduced their metabolically active iron pool. Importantly, Pfn2-deficient mice showed iron accumulation in discrete areas of the brain (olfactory bulb, hippocampus, and midbrain) and reduction of the hepatic iron store without anemia. Despite low liver iron levels, hepatic hepcidin expression remained high, likely because of compensatory activation of hepcidin by mild inflammation. Splenic ferroportin was increased probably to sustain hematopoiesis. Overall, our results indicate that Pfn2 expression is controlled by the IRPs in vivo and that Pfn2 contributes to maintaining iron homeostasis in cell lines and mice. © 2017 by The American Society of Hematology.

Enhanced transport of zerovalent iron nanoparticles in saturated porous media by guar gum

International Nuclear Information System (INIS)

Tiraferri, Alberto; Sethi, Rajandrea

2009-01-01

In order to ensure adequate mobility of zerovalent iron nanoparticles in natural aquifers, the use of a stabilizing agent is necessary. Polymers adsorbed on the nanoparticle surface will give rise to electrosteric stabilization and will decrease attachment to the surface soil grains. Water saturated sand-packed columns were used in this study to investigate the transport of iron nanoparticle suspensions, bare or modified with the green polymer guar gum. The suspensions were prepared at 154 mg/L particle concentration and 0.5 g/L polymer concentration. Transport experiments were conducted by varying the ionic strength, ionic composition, and approach velocity of the fluid. Nanoparticle deposition rates, attachment efficiencies, and travel distances were subsequently calculated based on the classical particle filtration theory. It was found that bare iron nanoparticles are basically immobile in sandy porous media. In contrast, guar gum is able to ensure significant nanoparticle transport at the tested conditions, regardless of the chemistry of the solution. Attachment efficiency values for guar gum-coated nanoparticles under the various conditions tested were smaller than 0.066. Although the calculated travel distances may not prove satisfactory for field application, the investigation attested the promising role of guar gum to ensure mobility of iron nanoparticles in the subsurface environment.

Iron is a substrate of the Plasmodium falciparum chloroquine resistance transporter PfCRT in Xenopus oocytes.

Science.gov (United States)

Bakouh, Naziha; Bellanca, Sebastiano; Nyboer, Britta; Moliner Cubel, Sonia; Karim, Zoubida; Sanchez, Cecilia P; Stein, Wilfred D; Planelles, Gabrielle; Lanzer, Michael

2017-09-29

The chloroquine resistance transporter of the human malaria parasite Plasmodium falciparum , PfCRT, is an important determinant of resistance to several quinoline and quinoline-like antimalarial drugs. PfCRT also plays an essential role in the physiology of the parasite during development inside erythrocytes. However, the function of this transporter besides its role in drug resistance is still unclear. Using electrophysiological and flux experiments conducted on PfCRT-expressing Xenopus laevis oocytes, we show here that both wild-type PfCRT and a PfCRT variant associated with chloroquine resistance transport both ferrous and ferric iron, albeit with different kinetics. In particular, we found that the ability to transport ferrous iron is reduced by the specific polymorphisms acquired by the PfCRT variant as a result of chloroquine selection. We further show that iron and chloroquine transport via PfCRT is electrogenic. If these findings in the Xenopus model extend to P. falciparum in vivo , our data suggest that PfCRT might play a role in iron homeostasis, which is essential for the parasite's development in erythrocytes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Possible evidence for transport of an iron cyanide complex by plants

International Nuclear Information System (INIS)

Samiotakis, M.; Ebbs, S.D.

2004-01-01

Barley (Hordeum vulgare L.), oat (Avena sativa L.), and wild cane (Sorghum bicolor L.), were exposed to 15 N-labeled ferrocyanide to determine whether these plant species can transport this iron cyanide complex. Plants were treated with ferrocyanide in a nutrient solution that simulated iron cyanide contaminated groundwater and soil solutions. This nutrient solution has been shown to maintain ferrocyanide speciation with minimal dissociation to free cyanide. Following treatment, all three plants showed dramatic enrichments in roots (δ 15 N%o=1000-1500) and shoots (δ 15 N%o=500). Barley and oat showed enrichment primarily in roots while wild cane showed a near equal enrichment in root and shoot tissues. Nitrogen-deficient barley plants treated with ferrocyanide showed a significantly greater 15 N enrichment as compared to nitrogen-sufficient plants. While the results are suggestive of ferrocyanide transport by these plant species, additional study will be required to verify these results. - Results suggest ferrocyanide transport by barley, oat and wild cane

Possible evidence for transport of an iron cyanide complex by plants

Energy Technology Data Exchange (ETDEWEB)

Samiotakis, M.; Ebbs, S.D

2004-01-01

Barley (Hordeum vulgare L.), oat (Avena sativa L.), and wild cane (Sorghum bicolor L.), were exposed to {sup 15}N-labeled ferrocyanide to determine whether these plant species can transport this iron cyanide complex. Plants were treated with ferrocyanide in a nutrient solution that simulated iron cyanide contaminated groundwater and soil solutions. This nutrient solution has been shown to maintain ferrocyanide speciation with minimal dissociation to free cyanide. Following treatment, all three plants showed dramatic enrichments in roots ({delta} {sup 15}N%o=1000-1500) and shoots ({delta} {sup 15}N%o=500). Barley and oat showed enrichment primarily in roots while wild cane showed a near equal enrichment in root and shoot tissues. Nitrogen-deficient barley plants treated with ferrocyanide showed a significantly greater {sup 15}N enrichment as compared to nitrogen-sufficient plants. While the results are suggestive of ferrocyanide transport by these plant species, additional study will be required to verify these results. - Results suggest ferrocyanide transport by barley, oat and wild cane.

Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a Spanish man.

Science.gov (United States)

Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Alvarez-Sala-Walther, Luis-Antonio; Cuadrado-Grande, Nuria; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

2011-03-01

The most common form of hemochromatosis is caused by mutations in the HFE gene. Rare forms of the disease are caused by mutations in other genes. We present a patient with hyperferritinemia and iron overload, and facial flushing. Magnetic resonance imaging was performed to measure hepatic iron overload, and a molecular study of the genes involved in iron metabolism was undertaken. The iron overload was similar to that observed in HFE hemochromatosis, and the patient was double heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and facial flushing improved after phlebotomy. Two of the patient's children were also studied, and the daughter was heterozygous for the mutation in the SLC40A1 gene, although she did not have hyperferritinemia. The patient presented a mild iron overload phenotype probably because of the two novel mutations in the HFE and SLC40A1 genes. © 2011 John Wiley & Sons A/S.

Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction.

Science.gov (United States)

Lee, Hyo Jung; Choi, Joo Sun; Lee, Hye Ja; Kim, Won-Ho; Park, Sang Ick; Song, Jihyun

2015-12-01

Excessive tissue iron levels are a risk factor for insulin resistance and type 2 diabetes, which are associated with alterations in iron metabolism. However, the mechanisms underlying this association are not well understood. This study used human liver SK-HEP-1 cells to examine how excess iron induces mitochondrial dysfunction and how hepcidin controls gluconeogenesis. Excess levels of reactive oxygen species (ROS) and accumulated iron due to iron overload induced mitochondrial dysfunction, leading to a decrease in cellular adenosine triphosphate content and cytochrome c oxidase III expression, with an associated increase in gluconeogenesis. Disturbances in mitochondrial function caused excess iron deposition and unbalanced expression of iron metabolism-related proteins such as hepcidin, ferritin H and ferroportin during the activation of p38 mitogen-activated protein kinase (MAPK) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are responsible for increased phosphoenolpyruvate carboxykinase expression. Desferoxamine and n-acetylcysteine ameliorated these deteriorations by inhibiting p38 MAPK and C/EBPα activity through iron chelation and ROS scavenging activity. Based on experiments using hepcidin shRNA and hepcidin overexpression, the activation of hepcidin affects ROS generation and iron deposition, which disturbs mitochondrial function and causes an imbalance in iron metabolism and increased gluconeogenesis. Repression of hepcidin activity can reverse these changes. Our results demonstrate that iron overload is associated with mitochondrial dysfunction and that together they can cause abnormal hepatic gluconeogenesis. Hepcidin expression may modulate this disorder by regulating ROS generation and iron deposition. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of H63D HFE gene carriage on hemoglobin and iron status in children.

Science.gov (United States)

Barbara, Kaczorowska-Hac; Marcin, Luszczyk; Jedrzej, Antosiewicz; Wieslaw, Ziolkowski; Elzbieta, Adamkiewicz-Drozynska; Malgorzata, Mysliwiec; Ewa, Milosz; Jacek, Kaczor Jan

2016-12-01

The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. Hereditary hemochromatosis is a heterogenic metabolic syndrome which is due to unchecked transfer of iron into the bloodstream and its toxic effects on parenchymatous organs. It is caused by the mutation of genes that encode proteins that help hepcidin to monitor serum iron. These proteins include the human hemochromatosis protein -HFE, transferrin-receptor 2, hemojuvelin in rare instances, and ferroportin. HFE-related hemochromatosis is the most frequent form of the disease. Interestingly, the low penetrance of polymorphic HFE genes results in rare clinical presentation of the disease, predominantly in middle-aged males. Taking into account the wide dispersion of HFE mutation in our population and also its unknown role in heterozygotes, we analyzed the impact of H63D HFE carriage in the developmental age, with respect to gender, on the iron status and hemoglobin concentration of carriers in comparison to those of wild-type HFE gene (12.7 ± 3.07 years, 42 boys and 41 girls). H63D carriers presented higher blood iron, transferrin saturation, and ferritin concentration than wild-type probands (p HFE heterozygotes.

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

Science.gov (United States)

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.

Indoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.

Science.gov (United States)

de Mattos Barbosa, Mayara Garcia; da Silva Prata, Rhana Berto; Andrade, Priscila Ribeiro; Ferreira, Helen; de Andrade Silva, Bruno Jorge; da Paixão de Oliveira, Jéssica Araújo; Assis, Tayná Quintella; de Toledo-Pinto, Thiago Gomes; de Lima Bezerra, Ohanna Cavalcanti; da Costa Nery, José Augusto; Rosa, Patricia Sammarco; Bozza, Marcelo Torres; Lara, Flávio Alves; Moraes, Milton Ozório; Schmitz, Veronica; Sarno, Euzenir Nunes; Pinheiro, Roberta Olmo

2017-11-01

Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO 4 stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. 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)

Fisiologia e metabolismo do ferro Iron physiology and metabolism

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Helena Z. W. Grotto

2010-06-01

Full Text Available O conhecimento sobre a fisiologia e metabolismo do ferro foi bastante incrementado nos últimos anos. A identificação de alguns genes e as repercussões quando de suas mutações, principalmente as relacionadas ao acúmulo de ferro, auxiliaram no entendimento dos mecanismos regulatórios responsáveis pela manutenção da homeostase desse nutriente essencial para numerosos processos bioquímicos. A função de diversas moléculas já está bem estabelecida, como da transferrina e seu receptor e, nas últimas décadas, novas moléculas têm sido identificadas, como a ferroportina, o transportador de metal divalente e hemojuvelina. Um elegante mecanismo de controle mantém o equilíbrio entre os processos de absorção do ferro, reciclagem, mobilização, utilização e estoque. Alterações no sincronismo desses processos podem causar tanto a deficiência como a sobrecarga de ferro, ambos com importantes repercussões clínicas para o paciente. Nessa minirrevisão serão abordados aspectos relacionados ao metabolismo do ferro e à participação de várias proteínas e mediadores envolvidos. Serão também apresentados os mecanismos regulatórios celular e sistêmico responsáveis pela disponibilidade do ferro em concentrações ideais para a manutenção de sua homeostase.Knowledge of the iron physiology and metabolism has increased greatly over the last few years. The identification of genes and the consequences of mutations, especially those related to the accumulation of iron, have improved the understanding of the regulatory mechanisms responsible for maintaining homeostasis of this essential nutrient in many biochemical processes. The function of several molecules is well established, as in the case of transferrin and its receptor and, in recent decades, new molecules have been identified such as ferroportin, divalent metal transporter, hemojuvelin and hepcidin. An elegant control mechanism maintains the balance between the processes of

Change in iron metabolism in rats after renal ischemia/reperfusion injury.

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Guang-Liang Xie

Full Text Available Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1 and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI. In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum creatinine and blood urea nitrogen were found to be time-dependently increased with different degrees of kidney injury. Regular variations in iron metabolism indexes in the blood and kidneys were observed in renal IRI. Renal iron content, serum iron and serum ferritin increased early after reperfusion and then declined. Hepcidin expression in the liver significantly increased early after reperfusion, and its serum concentration increased beginning at 8 h after reperfusion. The splenic iron content decreased significantly in the early stage after reperfusion and then increased time-dependently with increasing reperfusion time, and the hepatic iron content showed a decrease in the early stage after reperfusion. The early decrease of the splenic iron content and hepatic iron content might indicate their contribution to the increase in serum iron in renal IRI. In addition, the duodenal iron content showed time-dependently decreased since 12 h after reperfusion in the IRI groups compared to the control group. Along with the spleen, the duodenum might contribute to the decrease in serum iron in the later stage after reperfusion. The changes in iron metabolism indexes observed in our study demonstrate an iron metabolism disorder in renal IRI, and hepcidin might be involved in maintaining iron homeostasis in renal IRI. These

49 CFR 192.369 - Service lines: Connections to cast iron or ductile iron mains.

Science.gov (United States)

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Connections to cast iron or ductile iron mains. 192.369 Section 192.369 Transportation Other Regulations Relating to Transportation... ductile iron mains. (a) Each service line connected to a cast iron or ductile iron main must be connected...

Iron transport, deposition and bioavailability in the wheat and barley grain

DEFF Research Database (Denmark)

Borg, Søren; Brinch-Pedersen, Henrik; Tauris, Birgitte

2009-01-01

will briefly review existing knowledge on the distribution and transport pathways of iron in the two small grained cereals, barley and wheat, and focus on the efforts made to increase the iron content in cereals in general. However, mineral content is not the only factor of relevance for improving......). The nutritional impact of increasing mineral content accordingly has to be seen in the context of mineral bioavailability. Finally, we will briefly report on recent data from barley, where laser capture microdissection of the different grain tissues combined with gene expression profiling has provided some...

Biogeochemical reactive transport of carbon, nitrogen and iron in the hyporheic zone

Science.gov (United States)

Dwivedi, D.; Steefel, C. I.; Newcomer, M. E.; Arora, B.; Spycher, N.; Hammond, G. E.; Moulton, J. D.; Fox, P. M.; Nico, P. S.; Williams, K. H.; Dafflon, B.; Carroll, R. W. H.

2017-12-01

To understand how biogeochemical processes in the hyporheic zone influence carbon and nitrogen cycling as well as stream biogeochemistry, we developed a biotic and abiotic reaction network and integrated it into a reactive transport simulator - PFLOTRAN. Three-dimensional reactive flow and transport simulations were performed to describe the hyporheic exchange of fluxes from and within an intra-meander region encompassing two meanders of East River in the East Taylor watershed, Colorado. The objectives of this study were to quantify (1) the effect of transience on the export of carbon, nitrogen, and iron; and (2) the biogeochemical transformation of nitrogen and carbon species as a function of the residence time. The model was able to capture reasonably well the observed trends of nitrate and dissolved oxygen values that decreased as well as iron (Fe (II)) values that increased along the meander centerline away from the stream. Hyporheic flow paths create lateral redox zonation within intra-meander regions, which considerably impact nitrogen export into the stream system. Simulation results further demonstrated that low water conditions lead to higher levels of dissolved iron in groundwater, which (Fe (II)> 80%) is exported to the stream on the downstream side during high water conditions. An important conclusion from this study is that reactive transport models representing spatial and temporal heterogeneities are required to identify important factors that contribute to the redox gradients at riverine scales.

Copper and ectopic expression of the Arabidopsis transport protein COPT1 alter iron homeostasis in rice (Oryza sativa L.).

Science.gov (United States)

Andrés-Bordería, Amparo; Andrés, Fernando; Garcia-Molina, Antoni; Perea-García, Ana; Domingo, Concha; Puig, Sergi; Peñarrubia, Lola

2017-09-01

Copper deficiency and excess differentially affect iron homeostasis in rice and overexpression of the Arabidopsis high-affinity copper transporter COPT1 slightly increases endogenous iron concentration in rice grains. Higher plants have developed sophisticated mechanisms to efficiently acquire and use micronutrients such as copper and iron. However, the molecular mechanisms underlying the interaction between both metals remain poorly understood. In the present work, we study the effects produced on iron homeostasis by a wide range of copper concentrations in the growth media and by altered copper transport in Oryza sativa plants. Gene expression profiles in rice seedlings grown under copper excess show an altered expression of genes involved in iron homeostasis compared to standard control conditions. Thus, ferritin OsFER2 and ferredoxin OsFd1 mRNAs are down-regulated whereas the transcriptional iron regulator OsIRO2 and the nicotianamine synthase OsNAS2 mRNAs rise under copper excess. As expected, the expression of OsCOPT1, which encodes a high-affinity copper transport protein, as well as other copper-deficiency markers are down-regulated by copper. Furthermore, we show that Arabidopsis COPT1 overexpression (C1 OE ) in rice causes root shortening in high copper conditions and under iron deficiency. C1 OE rice plants modify the expression of the putative iron-sensing factors OsHRZ1 and OsHRZ2 and enhance the expression of OsIRO2 under copper excess, which suggests a role of copper transport in iron signaling. Importantly, the C1 OE rice plants grown on soil contain higher endogenous iron concentration than wild-type plants in both brown and white grains. Collectively, these results highlight the effects of rice copper status on iron homeostasis, which should be considered to obtain crops with optimized nutrient concentrations in edible parts.

Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract.

Science.gov (United States)

Niu, Qiang; He, Ping; Xu, Shangzhi; Ma, Ruling; Ding, Yusong; Mu, Lati; Li, Shugang

2018-01-01

Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

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...

Nitrate-dependent iron oxidation limits iron transport in anoxic ocean regions

Science.gov (United States)

Scholz, Florian; Löscher, Carolin R.; Fiskal, Annika; Sommer, Stefan; Hensen, Christian; Lomnitz, Ulrike; Wuttig, Kathrin; Göttlicher, Jörg; Kossel, Elke; Steininger, Ralph; Canfield, Donald E.

2016-11-01

Iron is an essential element for life on Earth and limits primary production in large parts of the ocean. Oxygen-free continental margin sediments represent an important source of bioavailable iron to the ocean, yet little of the iron released from the seabed reaches the productive sea surface. Even in the anoxic water of oxygen minimum zones, where iron solubility should be enhanced, most of the iron is rapidly re-precipitated. To constrain the mechanism(s) of iron removal in anoxic ocean regions we explored the sediment and water in the oxygen minimum zone off Peru. During our sampling campaign the water column featured two distinct redox boundaries separating oxic from nitrate-reducing (i.e., nitrogenous) water and nitrogenous from weakly sulfidic water. The sulfidic water mass in contact with the shelf sediment contained elevated iron concentrations >300 nM. At the boundary between sulfidic and nitrogenous conditions, iron concentrations dropped sharply to <20 nM coincident with a maximum in particulate iron concentration. Within the iron gradient, we found an increased expression of the key functional marker gene for nitrate reduction (narG). Part of this upregulation was related to the activity of known iron-oxidizing bacteria. Collectively, our data suggest that iron oxidation and removal is induced by nitrate-reducing microbes, either enzymatically through anaerobic iron oxidation or by providing nitrite for an abiotic reaction. Given the important role that iron plays in nitrogen fixation, photosynthesis and respiration, nitrate-dependent iron oxidation likely represents a key-link between the marine biogeochemical cycles of nitrogen, oxygen and carbon.

Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

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Sara Pizzamiglio

2017-02-01

Full Text Available We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA or reverse-phase protein array (RPPA, were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012. The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5, signal transducer and activator of transcription 3 (STAT3, bone morphogenetic protein 6 (BMP6, cluster of differentiation 74 (CD74, transferrin receptor (TFRC, inhibin alpha (INHA, and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88, CD74, iron exporter ferroportin (FPN, high mobility group box 1 (HMGB1, STAT3_pS727, TFRC, ferritin heavy chain (FTH, and ferritin light chain (FTL. Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer.

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

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.

Hereditary hemochromatosis: An opportunity for gene therapy

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FERNANDO EZQUER

2006-01-01

Full Text Available Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1 transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytes

Humic acid facilitates the transport of ARS-labeled hydroxyapatite nanoparticles in iron oxyhydroxide-coated sand

Science.gov (United States)

Wang, Dengjun; Bradford, Scott A.; Harvey, Ronald W.; Gao, Bin; Cang, Long; Zhou, Dongmei

2012-01-01

Hydroxyapatite nanoparticles (nHAP) have been widely used to remediate soil and wastewater contaminated with metals and radionuclides. However, our understanding of nHAP transport and fate is limited in natural environments that exhibit significant variability in solid and solution chemistry. The transport and retention kinetics of Alizarin red S (ARS)-labeled nHAP were investigated in water-saturated packed columns that encompassed a range of humic acid concentrations (HA, 0–10 mg L–1), fractional surface coverage of iron oxyhydroxide coatings on sand grains (λ, 0–0.75), and pH (6.0–10.5). HA was found to have a marked effect on the electrokinetic properties of ARS-nHAP, and on the transport and retention of ARS-nHAP in granular media. The transport of ARS-nHAP was found to increase with increasing HA concentration because of enhanced colloidal stability and the reduced aggregate size. When HA = 10 mg L–1, greater ARS-nHAP attachment occurred with increasing λ because of increased electrostatic attraction between negatively charged nanoparticles and positively charged iron oxyhydroxides, although alkaline conditions (pH 8.0 and 10.5) reversed the surface charge of the iron oxyhydroxides and therefore decreased deposition. The retention profiles of ARS-nHAP exhibited a hyperexponential shape for all test conditions, suggesting some unfavorable attachment conditions. Retarded breakthrough curves occurred in sands with iron oxyhydroxide coatings because of time-dependent occupation of favorable deposition sites. Consideration of the above effects is necessary to improve remediation efficiency of nHAP for metals and actinides in soils and subsurface environments.

Magnetic resonance microscopy of iron transport in methanogenic granules

Science.gov (United States)

Bartacek, Jan; Vergeldt, Frank J.; Gerkema, Edo; Jenicek, Pavel; Lens, Piet N. L.; Van As, Henk

2009-10-01

Interactions between anaerobic biofilms and heavy metals such as iron, cobalt or nickel are largely unknown. Magnetic resonance imaging (MRI) is a non-invasive method that allows in situ studies of metal transport within biofilm matrixes. The present study investigates quantitatively the penetration of iron (1.75 mM) bound to ethylenediaminetetraacetate (EDTA) into the methanogenic granules (spherical biofilm). A spatial resolution of 109 × 109 × 218 μm 3 and a temporal resolution of 11 min are achieved with 3D Turbo Spin Echo (TSE) measurements. The longitudinal relaxivity, i.e. the slope the dependence of the relaxation rate (1/ T1) on the concentration of paramagnetic metal ions, was used to measure temporal changes in iron concentration in the methanogenic granules. It took up to 300 min for the iron-EDTA complex ([FeEDTA] 2-) to penetrate into the methanogenic granules (3-4 mm in diameter). The diffusion was equally fast in all directions with irregularities such as diffusion-facilitating channels and diffusion-resistant zones. Despite these irregularities, the overall process could be modeled using Fick's equations for diffusion in a sphere, because immobilization of [FeEDTA] 2- in the granular matrix (or the presence of a reactive barrier) was not observed. The effective diffusion coefficient ( D ejf) of [FeEDTA] 2- was found to be 2.8 × 10 -11 m 2 s -1, i.e. approximately 4% of D ejf of [FeEDTA] 2- in water. The Fickian model did not correspond to the processes taking place in the core of the granule (3-5% of the total volume of the granule), where up to 25% over-saturation by iron (compare to the concentration in the bulk solution) occurred.

Interacting Effects of Light and Iron Availability on the Coupling of Photosynthetic Electron Transport and CO2-Assimilation in Marine Phytoplankton.

Science.gov (United States)

Schuback, Nina; Schallenberg, Christina; Duckham, Carolyn; Maldonado, Maria T; Tortell, Philippe D

2015-01-01

Iron availability directly affects photosynthesis and limits phytoplankton growth over vast oceanic regions. For this reason, the availability of iron is a crucial variable to consider in the development of active chlorophyll a fluorescence based estimates of phytoplankton primary productivity. These bio-optical approaches require a conversion factor to derive ecologically-relevant rates of CO2-assimilation from estimates of electron transport in photosystem II. The required conversion factor varies significantly across phytoplankton taxa and environmental conditions, but little information is available on its response to iron limitation. In this study, we examine the role of iron limitation, and the interacting effects of iron and light availability, on the coupling of photosynthetic electron transport and CO2-assimilation in marine phytoplankton. Our results show that excess irradiance causes increased decoupling of carbon fixation and electron transport, particularly under iron limiting conditions. We observed that reaction center II specific rates of electron transport (ETR(RCII), mol e- mol RCII(-1) s(-1)) increased under iron limitation, and we propose a simple conceptual model for this observation. We also observed a strong correlation between the derived conversion factor and the expression of non-photochemical quenching. Utilizing a dataset from in situ phytoplankton assemblages across a coastal--oceanic transect in the Northeast subarctic Pacific, this relationship was used to predict ETR(RCII): CO2-assimilation conversion factors and carbon-based primary productivity from FRRF data, without the need for any additional measurements.

Interacting Effects of Light and Iron Availability on the Coupling of Photosynthetic Electron Transport and CO2-Assimilation in Marine Phytoplankton.

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Nina Schuback

Full Text Available Iron availability directly affects photosynthesis and limits phytoplankton growth over vast oceanic regions. For this reason, the availability of iron is a crucial variable to consider in the development of active chlorophyll a fluorescence based estimates of phytoplankton primary productivity. These bio-optical approaches require a conversion factor to derive ecologically-relevant rates of CO2-assimilation from estimates of electron transport in photosystem II. The required conversion factor varies significantly across phytoplankton taxa and environmental conditions, but little information is available on its response to iron limitation. In this study, we examine the role of iron limitation, and the interacting effects of iron and light availability, on the coupling of photosynthetic electron transport and CO2-assimilation in marine phytoplankton. Our results show that excess irradiance causes increased decoupling of carbon fixation and electron transport, particularly under iron limiting conditions. We observed that reaction center II specific rates of electron transport (ETR(RCII, mol e- mol RCII(-1 s(-1 increased under iron limitation, and we propose a simple conceptual model for this observation. We also observed a strong correlation between the derived conversion factor and the expression of non-photochemical quenching. Utilizing a dataset from in situ phytoplankton assemblages across a coastal--oceanic transect in the Northeast subarctic Pacific, this relationship was used to predict ETR(RCII: CO2-assimilation conversion factors and carbon-based primary productivity from FRRF data, without the need for any additional measurements.

Interacting Effects of Light and Iron Availability on the Coupling of Photosynthetic Electron Transport and CO2-Assimilation in Marine Phytoplankton

Science.gov (United States)

Schuback, Nina; Schallenberg, Christina; Duckham, Carolyn; Maldonado, Maria T.; Tortell, Philippe D.

2015-01-01

Iron availability directly affects photosynthesis and limits phytoplankton growth over vast oceanic regions. For this reason, the availability of iron is a crucial variable to consider in the development of active chlorophyll a fluorescence based estimates of phytoplankton primary productivity. These bio-optical approaches require a conversion factor to derive ecologically-relevant rates of CO2-assimilation from estimates of electron transport in photosystem II. The required conversion factor varies significantly across phytoplankton taxa and environmental conditions, but little information is available on its response to iron limitation. In this study, we examine the role of iron limitation, and the interacting effects of iron and light availability, on the coupling of photosynthetic electron transport and CO2-assimilation in marine phytoplankton. Our results show that excess irradiance causes increased decoupling of carbon fixation and electron transport, particularly under iron limiting conditions. We observed that reaction center II specific rates of electron transport (ETRRCII, mol e- mol RCII-1 s-1) increased under iron limitation, and we propose a simple conceptual model for this observation. We also observed a strong correlation between the derived conversion factor and the expression of non-photochemical quenching. Utilizing a dataset from in situ phytoplankton assemblages across a coastal – oceanic transect in the Northeast subarctic Pacific, this relationship was used to predict ETRRCII: CO2-assimilation conversion factors and carbon-based primary productivity from FRRF data, without the need for any additional measurements. PMID:26171963

Linking carbon and iron cycles by investigating transport, fate and mineralogy of iron-bearing colloids from peat-draining rivers - Scotland as model for high-latitude rivers

Science.gov (United States)

Wood, Deborah; Crocket, Kirsty; Brand, Tim; Stutter, Marc; Wilson, Clare; Schröder, Christian

2016-04-01

Linking carbon and iron cycles by investigating transport, fate and mineralogy of iron-bearing colloids from peat-draining rivers - Scotland as model for high-latitude rivers Wood, D.A¹, Crocket, K², Brand, T², Stutter, M³, Wilson, C¹ & Schröder, C¹ ¹Biological and Environmental Sciences, University of Stirling, Stirling, FK9 4LA ²Scottish Association for Marine Science, University of the Highlands and Islands, Dunbeg, Oban, PA37 1QA ³James Hutton Institute, Craigiebuckler, Aberdeen, AB15 8QH The biogeochemical iron cycle exerts significant control on the carbon cycle¹. Iron is a limiting nutrient in large areas of the world's oceans and its bioavailability controls CO2 uptake by marine photosynthesizing microorganisms. While atmospheric iron inputs to the open ocean have been extensively measured, global river inputs have likely been underestimated because most major world rivers exhibit extensive iron removal by flocculation and sedimentation during seawater mixing. Iron minerals and organic matter mutually stabilise each other², which results in a 'rusty carbon sink' in sediments³ on the one hand but may also enhance transport beyond the salinity gradient on the other. Humic-rich, high latitude rivers have a higher iron-carrying capacity⁴-⁶ but are underrepresented in iron flux calculations. The West Coast sea lochs in Scotland are fed by predominantly peatland drainage catchments, and the rivers entering the sea lochs carry a high load of organic matter. The short distance between many of these catchments and the coastal ocean facilitates source-to-sea research investigating transport, fate and mineralogy of iron-bearing colloids providing a good analogue for similar high latitude fjordic systems. We use SeaFAST+ICP-MS and Mössbauer spectroscopy to survey trace metal concentrations, with emphasis on iron concentrations, speciation and mineralogy, across salinity gradients. In combination with ultra-filtration techniques, this allows

49 CFR 192.373 - Service lines: Cast iron and ductile iron.

Science.gov (United States)

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Cast iron and ductile iron. 192.373... Regulators, and Service Lines § 192.373 Service lines: Cast iron and ductile iron. (a) Cast or ductile iron... cast iron pipe or ductile iron pipe is installed for use as a service line, the part of the service...

49 CFR 192.277 - Ductile iron pipe.

Science.gov (United States)

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Ductile iron pipe. 192.277 Section 192.277 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Ductile iron pipe. (a) Ductile iron pipe may not be joined by threaded joints. (b) Ductile iron pipe may...

Nitrate-dependent iron oxidation limits iron transport in anoxic ocean regions

DEFF Research Database (Denmark)

Scholz, Florian; Löscher, Carolin; Fiskal, Annika

2016-01-01

Iron is an essential element for life on Earth and limits primary production in large parts of the ocean. Oxygen-free continental margin sediments represent an important source of bioavailable iron to the ocean, yet little of the iron released from the seabed reaches the productive sea surface...

Liver ischemia and ischemia-reperfusion induces and trafficks the multi-specific metal transporter Atp7b to bile duct canaliculi: possible preferential transport of iron into bile.

Science.gov (United States)

Goss, John A; Barshes, Neal R; Karpen, Saul J; Gao, Feng-Qin; Wyllie, Samuel

2008-04-01

Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia-reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia-reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia-reperfusion. Thus, we conclude that liver ischemia and ischemia-reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile.

Intestinal Iron Homeostasis and Colon Tumorigenesis

Directory of Open Access Journals (Sweden)

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.

49 CFR 192.489 - Remedial measures: Cast iron and ductile iron pipelines.

Science.gov (United States)

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Remedial measures: Cast iron and ductile iron... for Corrosion Control § 192.489 Remedial measures: Cast iron and ductile iron pipelines. (a) General graphitization. Each segment of cast iron or ductile iron pipe on which general graphitization is found to a...

Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice.

Science.gov (United States)

De Domenico, Ivana; Zhang, Tian Y; Koening, Curry L; Branch, Ryan W; London, Nyall; Lo, Eric; Daynes, Raymond A; Kushner, James P; Li, Dean; Ward, Diane M; Kaplan, Jerry

2010-07-01

Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-alpha transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses.

Aluminum stimulates uptake of non-transferrin bound iron and transferrin bound iron in human glial cells

International Nuclear Information System (INIS)

Kim, Yongbae; Olivi, Luisa; Cheong, Jae Hoon; Maertens, Alex; Bressler, Joseph P.

2007-01-01

Aluminum and other trivalent metals were shown to stimulate uptake of transferrin bound iron and nontransferrin bound iron in erytholeukemia and hepatoma cells. Because of the association between aluminum and Alzheimer's Disease, and findings of higher levels of iron in Alzheimer's disease brains, the effects of aluminum on iron homeostasis were examined in a human glial cell line. Aluminum stimulated dose- and time-dependent uptake of nontransferrin bound iron and iron bound to transferrin. A transporter was likely involved in the uptake of nontransferrin iron because uptake reached saturation, was temperature-dependent, and attenuated by inhibitors of protein synthesis. Interestingly, the effects of aluminum were not blocked by inhibitors of RNA synthesis. Aluminum also decreased the amount of iron bound to ferritin though it did not affect levels of divalent metal transporter 1. These results suggest that aluminum disrupts iron homeostasis in Brain by several mechanisms including the transferrin receptor, a nontransferrin iron transporter, and ferritin

Dissolved iron anomaly in the deep tropical-subtropical Pacific: Evidence for long-range transport of hydrothermal iron

Science.gov (United States)

Wu, Jingfeng; Wells, Mark L.; Rember, Robert

2011-01-01

Dissolved iron profiles along a north-south transect along 158°W in the tropical Pacific show evidence of two deepwater anomalies. The first extends from Station ALOHA (22.78°N) to the equator at ˜1000-1500 m and lies below the maximum apparent oxygen utilization and nutrient (N, P) concentrations. The feature is not supported by vertical export processes, but instead corresponds with the lateral dilution field of δ 3He derived from the Loihi seamount, Hawaii, though a sediment source associated with the Hawaiian Island Chain cannot be entirely ruled out. The second, deeper (2000-3000 m) anomaly occurs in tropical South Pacific waters (7°S) and also does not correlate with the depths of maximum nutrient concentrations or apparent oxygen utilization, but it does coincide closely with δ 3He emanating from the East Pacific Rise, more than 5000 km to the east. We hypothesize that these anomalies represent the long-range (>2000 km) transport of hydrothermal iron residuals, stabilized against scavenging by complexation with excess organic ligands in the plume source regions. Such trace leakage of hydrothermal iron to distal plume regions would have been difficult to identify in most hydrothermal vent mapping studies because low analytical detection limits were not needed for the proximal plume regions. These findings suggest that hydrothermal activity may represent a major source of dissolved iron throughout the South Pacific deep basin today, as well as other regions having high mid-ocean spreading rates in the geologic past. In particular, we hypothesize that high spreading rates along the South Atlantic and Southern Ocean mid-oceanic ridges, combined with the upwelling ventilation of these distal hydrothermal plumes, may have increased ocean productivity and carbon export in the Southern Ocean. Assessing the magnitude and persistence of dissolved hydrothermal iron in basin scale deep waters will be important for understanding the marine biogeochemistry of iron

Iron-hydroxamate transport in Escherichia coli K12

International Nuclear Information System (INIS)

Prody, C.A.

1984-01-01

FhuB mutants, which are deficient in ferrichrome transport, were isolated and characterized. They were found to be deficient in the utilization of all hydroxamate-type siderophores. They were, however, able to transport enterobactin. A number of analogs of hydroxamate-type siderophores were tested for biological activity in E. coli, and about half of these were active. In addition, two rhodotorulic acid analogs were able to supply iron to fhuB mutants. A search for the fhuB gene product, using one and two-dimensional polyacrylamide gels of proteins from fhuB and wild type strains proved fruitless, and it appeared that the fhuB gene product is expressed at a very low level. Therefore, the fhuB gene was subcloned from a plasmid in the Carbon bank onto plasmid vectors containing the E. coli lac UV-5 and tacI promoters as a device to amplify the fhuB gene. One of these recombinant plasmids carried an 8Kb insert which contained both the tonA and fhuB genes. This plasmid synthesized five proteins of molecular weights 78,000, 40,000, 30,000, 24,000, and 13,700 in maxicell strain CSR603. By use of deletions, the approximate order of the genes for these proteins was determined. Although 3 He-ferrichrome is transported into E. coli cells and vesicles, 3 He-ferric rhodotorulate is not, and so the mechanism of transport for these two siderophores must be different. To examine this further, mutants were obtained that could transport ferrichrome but not rhodotorulic acid. These map in the region between tonA and fhuB, and most are able to transport aerobactin, when carrying the ColV plasmid, but not schizokinen

Specific expression of the vacuolar iron transporter, TgVit, causes iron accumulation in blue-colored inner bottom segments of various tulip petals.

Science.gov (United States)

Momonoi, Kazumi; Tsuji, Toshiaki; Kazuma, Kohei; Yoshida, Kumi

2012-01-01

Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue-specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth.

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.

Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: a conceptual framework.

Science.gov (United States)

Hamad, Mawieh; Awadallah, Samir

2013-12-01

Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels

Energy Technology Data Exchange (ETDEWEB)

Kayaaltı, Zeliha, E-mail: kayaalti@ankara.edu.tr; Akyüzlü, Dilek Kaya; Söylemezoğlu, Tülin

2015-02-15

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metal trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01±81.87 ppm, 35.59±17.72 ppb and 1.25±0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels. - Highlights: • DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, cadmium and lead levels. �

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels

International Nuclear Information System (INIS)

Kayaaltı, Zeliha; Akyüzlü, Dilek Kaya; Söylemezoğlu, Tülin

2015-01-01

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metal trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01±81.87 ppm, 35.59±17.72 ppb and 1.25±0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels. - Highlights: • DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, cadmium and lead levels. �

High bioavailablilty iron maize (Zea mays L.) developed through molecular breeding provides more absorbable iron in vitro (Caco-2 model) and in vivo (Gallus gallus)

Science.gov (United States)

2013-01-01

Background Iron (Fe) deficiency is the most common micronutrient deficiency worldwide. Iron biofortification is a preventative strategy that alleviates Fe deficiency by improving the amount of absorbable Fe in crops. In the present study, we used an in vitro digestion/Caco 2 cell culture model as the guiding tool for breeding and development of two maize (Zea mays L.) lines with contrasting Fe bioavailability (ie. Low and High). Our objective was to confirm and validate the in vitro results and approach. Also, to compare the capacities of our two maize hybrid varieties to deliver Fe for hemoglobin (Hb) synthesis and to improve the Fe status of Fe deficient broiler chickens. Methods We compared the Fe-bioavailability between these two maize varieties with the presence or absence of added Fe in the maize based-diets. Diets were made with 75% (w/w) maize of either low or high Fe-bioavailability maize, with or without Fe (ferric citrate). Chicks (Gallus gallus) were fed the diets for 6 wk. Hb, liver ferritin and Fe related transporter/enzyme gene-expression were measured. Hemoglobin maintenance efficiency (HME) and total body Hb Fe values were used to estimate Fe bioavailability from the diets. Results DMT-1, DcytB and ferroportin expressions were higher (P < 0.05) in the "Low Fe" group than in the "High Fe" group (no added Fe), indicating lower Fe status and adaptation to less Fe-bioavailability. At times, Hb concentrations (d 21,28,35), HME (d 21), Hb-Fe (as from d 14) and liver ferritin were higher in the "High Fe" than in the "Low Fe" groups (P < 0.05), indicating greater Fe absorption from the diet and improved Fe status. Conclusions We conclude that the High Fe-bioavailability maize contains more bioavailable Fe than the Low Fe-bioavailability maize, presumably due to a more favorable matrix for absorption. Maize shows promise for Fe biofortification; therefore, human trials should be conducted to determine the efficacy of consuming the high bioavailable

Transport measurements on superconducting iron pnictides and Heusler compounds; Transportmessungen an Supraleitenden Eisenpniktiden und Heusler-Verbindungen

Energy Technology Data Exchange (ETDEWEB)

Bombor, Dirk

2014-09-05

In this work, results of electronic transport measurements are discussed for superconducting iron pnictides as well as for ferromagnetic Heusler compounds. The iron pnictides are a recently discovered class of high temperature superconductors where magnetism might play a crucial role. While the 122-pnictides show antiferromagnetism and migrate to the superconducting state upon doping, ferromagnetism has been observed in doped LiFeAs. On the other hand, in the undoped state this material shows interesting superconducting properties. Among other properties, Heusler compounds are well known due to their ferromagnetism. Co{sub 2}FeSi, which was investigated in this work, is one of the strongest ferromagnets. Beside this, one predicts this compound to be a half-metallic ferromagnet with completely spin polarized electronic transport where all conducting electrons have the same spin. The here addressed properties can well be investigated with the method of electronic transport measurements, whose results on single crystals are discussed in this work.

Nutrient transport in the mammary gland: calcium, trace minerals and water soluble vitamins.

Science.gov (United States)

Montalbetti, Nicolas; Dalghi, Marianela G; Albrecht, Christiane; Hediger, Matthias A

2014-03-01

Milk nutrients are secreted by epithelial cells in the alveoli of the mammary gland by several complex and highly coordinated systems. Many of these nutrients are transported from the blood to the milk via transcellular pathways that involve the concerted activity of transport proteins on the apical and basolateral membranes of mammary epithelial cells. In this review, we focus on transport mechanisms that contribute to the secretion of calcium, trace minerals and water soluble vitamins into milk with particular focus on the role of transporters of the SLC series as well as calcium transport proteins (ion channels and pumps). Numerous members of the SLC family are involved in the regulation of essential nutrients in the milk, such as the divalent metal transporter-1 (SLC11A2), ferroportin-1 (SLC40A1) and the copper transporter CTR1 (SLC31A1). A deeper understanding of the physiology and pathophysiology of these transporters will be of great value for drug discovery and treatment of breast diseases.

A hepcidina como parâmetro bioquímico na avaliação da anemia por deficiência de ferro Hepcidin as a biochemical parameter for the assessment of iron deficiency anemia

Directory of Open Access Journals (Sweden)

Andrea dos Reis Lemos

2010-01-01

parameter for assessment of iron deficiency anemia is reported in this review. A literature review was carried out in the databases PubMed and LILACS, between 2006-2010, assessing hepcidin as a parameter for the regulation of iron metabolism. During this period 35 studies were published in international journals and one study in a Brazilian journal. The production of hepcidin is homeostatically regulated by anemia and hypoxia. When oxygen supply is inadequate the level of hepcidin decreases. Therefore, more iron from the diet and from the stock of macrophages and hepatocytes becomes available. Hepcidin links to ferroportin, regulating iron release to plasma. When the hepcidin concentrations are low, the molecules of ferroportin are exposed on the plasmatic membrane and release iron. When hepcidin levels increase, hepcidin binds to molecules of ferroportin inducing its internalization and degradation and iron release gradually decreases. Apparently, development of diagnosis and therapy for anemia based on the parameter hepcidin may provide a more effective approach. Large-studies are needed to demonstrate the importance of hepcidin for the differential diagnosis of anemia, including sample protocols for analysis, with standards similar to those used in other biochemical evaluations, as well as the definition of cut-off points for the plasma and urinary expression of this peptide.

49 CFR 192.487 - Remedial measures: Distribution lines other than cast iron or ductile iron lines.

Science.gov (United States)

2010-10-01

... cast iron or ductile iron lines. 192.487 Section 192.487 Transportation Other Regulations Relating to... iron or ductile iron lines. (a) General corrosion. Except for cast iron or ductile iron pipe, each... the purpose of this paragraph. (b) Localized corrosion pitting. Except for cast iron or ductile iron...

Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines

DEFF Research Database (Denmark)

Hansen, Jakob Bondo; Tonnesen, Morten Fog; Madsen, Andreas Nygaard

2012-01-01

Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Little is known about iron transport regulation during inflammatory attack. Through a combination of in vitro and in vivo studies, we show that the proinflammatory cytokine IL-1ß induces...... knockout islets is defective, highlighting a physiological role of iron and ROS in the regulation of insulin secretion. Dmt1 knockout mice are protected against multiple low-dose streptozotocin and high-fat diet-induced glucose intolerance, models of type 1 and type 2 diabetes, respectively. Thus, ß cells...

Controls on radium transport by adsorption to iron minerals

Science.gov (United States)

Chen, M.; Wang, T.; Kocar, B. D.

2015-12-01

Radium is a naturally occurring radioactive metal found in many subsurface environments. Radium isotopes are generated by uranium and thorium decay, and are particularly abundant within groundwaters where minimal porewater flux leads to accumulation. These isotopes are used as natural tracers for estimating submarine groundwater discharge (SGD) [1], allowing for large scale estimation of GW fluxes into and out of the ocean [2]. They also represent a substantial hazard in wastewater produced after hydraulic fracturing for natural gas extraction [3], resulting in a significant risk of environmental release to surface and near-surface waters, and increased cost for water treatment or disposal. Adsorption to mineral surfaces represents a dominant pathway of radium retention in subsurface environments. For SGD studies, adsorption processes impact estimates of GW fluxes, while in hydraulic fracturing, radium adsorption to aquifer solids mediates wastewater radium activities. Analysis of past sorption studies revealed large variability in partition coefficients [4], while examination of radium adsorption kinetics and surface complexation have only recently started [5]. Accordingly, we present the results of sorption and column experiments of radium with a suite of iron minerals representative of those found within deep saline and near-surface (freshwater) aquifers, and evaluate impacts of varying salinity solutions through artificial waters. Further, we explore the impacts of pyrite oxidation and ferrihydrite transformation to other iron-bearing secondary minerals on the transport and retention of radium. These results will provide critical information on the mineralogical controls on radium retention in subsurface environments, and will therefore improve predictions of radium groundwater transport in natural and contaminated systems. [1] Charette, M.A., Buesseler, K.O. & Andrews, J.E., Limnol. Oceanogr. (2001). [2] Moore, W.S., Ann. Rev. Mar. Sci. (2010). [3] Vengosh, A

Subcellular Iron Localization Mechanisms in Plants

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

Modelling of neutron and photon transport in iron and concrete radiation shieldings by the Monte Carlo method - Version 2

CERN Document Server

Žukauskaite, A; Plukiene, R; Plukis, A

2007-01-01

Particle accelerators and other high energy facilities produce penetrating ionizing radiation (neutrons and γ-rays) that must be shielded. The objective of this work was to model photon and neutron transport in various materials, usually used as shielding, such as concrete, iron or graphite. Monte Carlo method allows obtaining answers by simulating individual particles and recording some aspects of their average behavior. In this work several nuclear experiments were modeled: AVF 65 – γ-ray beams (1-10 MeV), HIMAC and ISIS-800 – high energy neutrons (20-800 MeV) transport in iron and concrete. The results were then compared with experimental data.

Gibberellins regulate iron deficiency-response by influencing iron transport and translocation in rice seedlings (Oryza sativa).

Science.gov (United States)

Wang, Baolan; Wei, Haifang; Xue, Zhen; Zhang, Wen-Hao

2017-04-01

Gibberellins (GAs) are a class of plant hormones with diverse functions. However, there has been little information on the role of GAs in response to plant nutrient deficiency. To evaluate the roles of GAs in regulation of Fe homeostasis, the effects of GA on Fe accumulation and Fe translocation in rice seedlings were investigated using wild-type, a rice mutant ( eui1 ) displaying enhnaced endogenous GA concentrations due to a defect in GA deactivation, and transgenic rice plants overexpressing OsEUI . Exposure to Fe-deficient medium significantly reduced biomass of rice plants. Both exogenous application of GA and an endogenous increase of bioactive GA enhanced Fe-deficiency response by exaggerating foliar chlorosis and reducing growth. Iron deficiency significantly suppressed production of GA 1 and GA 4 , the biologically active GAs in rice. Exogenous application of GA significantly decreased leaf Fe concentration regardless of Fe supply. Iron concentration in shoot of eui1 mutants was lower than that of WT plants under both Fe-sufficient and Fe-deficient conditions. Paclobutrazol, an inhibitor of GA biosynthesis, alleviated Fe-deficiency responses, and overexpression of EUI significantly increased Fe concentration in shoots and roots. Furthermore, both exogenous application of GA and endogenous increase in GA resulting from EUI mutation inhibited Fe translocation within shoots by suppressing OsYSL2 expression, which is involved in Fe transport and translocation. The novel findings provide compelling evidence to support the involvement of GA in mediation of Fe homeostasis in strategy II rice plants by negatively regulating Fe transport and translocation. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Helium, Iron and Electron Particle Transport and Energy Transport Studies on the TFTR Tokamak

Science.gov (United States)

Synakowski, E. J.; Efthimion, P. C.; Rewoldt, G.; Stratton, B. C.; Tang, W. M.; Grek, B.; Hill, K. W.; Hulse, R. A.; Johnson, D .W.; Mansfield, D. K.; McCune, D.; Mikkelsen, D. R.; Park, H. K.; Ramsey, A. T.; Redi, M. H.; Scott, S. D.; Taylor, G.; Timberlake, J.; Zarnstorff, M. C. (Princeton Univ., NJ (United States). Plasma Physics Lab.); Kissick, M. W. (Wisconsin Univ., Madison, WI (United States))

1993-03-01

Results from helium, iron, and electron transport on TFTR in L-mode and Supershot deuterium plasmas with the same toroidal field, plasma current, and neutral beam heating power are presented. They are compared to results from thermal transport analysis based on power balance. Particle diffusivities and thermal conductivities are radially hollow and larger than neoclassical values, except possibly near the magnetic axis. The ion channel dominates over the electron channel in both particle and thermal diffusion. A peaked helium profile, supported by inward convection that is stronger than predicted by neoclassical theory, is measured in the Supershot The helium profile shape is consistent with predictions from quasilinear electrostatic drift-wave theory. While the perturbative particle diffusion coefficients of all three species are similar in the Supershot, differences are found in the L-Mode. Quasilinear theory calculations of the ratios of impurity diffusivities are in good accord with measurements. Theory estimates indicate that the ion heat flux should be larger than the electron heat flux, consistent with power balance analysis. However, theoretical values of the ratio of the ion to electron heat flux can be more than a factor of three larger than experimental values. A correlation between helium diffusion and ion thermal transport is observed and has favorable implications for sustained ignition of a tokamak fusion reactor.

Helium, iron and electron particle transport and energy transport studies on the TFTR tokamak

International Nuclear Information System (INIS)

Synakowski, E.J.; Efthimion, P.C.; Rewoldt, G.; Stratton, B.C.; Tang, W.M.; Grek, B.; Hill, K.W.; Hulse, R.A.; Johnson, D.W.; Mansfield, D.K.; McCune, D.; Mikkelsen, D.R.; Park, H.K.; Ramsey, A.T.; Redi, M.H.; Scott, S.D.; Taylor, G.; Timberlake, J.; Zarnstorff, M.C.

1993-03-01

Results from helium, iron, and electron transport on TFTR in L-mode and Supershot deuterium plasmas with the same toroidal field, plasma current, and neutral beam heating power are presented. They are compared to results from thermal transport analysis based on power balance. Particle diffusivities and thermal conductivities are radially hollow and larger than neoclassical values, except possibly near the magnetic axis. The ion channel dominates over the electron channel in both particle and thermal diffusion. A peaked helium profile, supported by inward convection that is stronger than predicted by neoclassical theory, is measured in the Supershot The helium profile shape is consistent with predictions from quasilinear electrostatic drift-wave theory. While the perturbative particle diffusion coefficients of all three species are similar in the Supershot, differences are found in the L-Mode. Quasilinear theory calculations of the ratios of impurity diffusivities are in good accord with measurements. Theory estimates indicate that the ion heat flux should be larger than the electron heat flux, consistent with power balance analysis. However, theoretical values of the ratio of the ion to electron heat flux can be more than a factor of three larger than experimental values. A correlation between helium diffusion and ion thermal transport is observed and has favorable implications for sustained ignition of a tokamak fusion reactor

Influence of food tannins on certain aspects of iron metabolism : Part 2 -- Storage and transport in normal and anemic rats

Energy Technology Data Exchange (ETDEWEB)

Roy, S N [Albert Einstein Coll. of Medicine, Bronx, NY (USA); Mukherjee, S [Calcutta Univ. (India). Dept. of Applied Chemistry

1979-04-01

Administration of tannin (0.5 mg/kg body wt/day) from fruits and vegetables lowers the iron content in liver, spleen and bone marrow with an elevation in Total Iron Binding Capacity (TIBC) of serum and serum iron concentration in normal rats. The same dose of tannin increases the iron content in storage tissues, particularly bone marrow of hemolytic anemic rats. In anemic rats, TIBC is decreased and serum iron concentration is raised from anemic level to approximately normal value due to ingestion of tannin. Radioiron administration, either by oral or by intravenous route, also elicits similar results. Recovery of iron storage and transport values from the anemic to the normal condition by tannin (0.5 mg/kg) varies with the source of tannin used. Thus more iron required for compensating the anemic conditions is retained within their body by tannin (0.5 mg/kg) which appears to reduce the loss of peripheral iron probably by protecting the lysis of red cells.

An outsider's perspective--ecotaxis revisited: an integrative review of cancer environment, iron and immune system cells.

Science.gov (United States)

de Sousa, Maria

2011-04-01

Lymphoid cell and tumor cell migration share similarities: 1. migration to specific microenvironments; 2. increased microvasculature with increased growth; 3. cell division. At the same time, contrasting aspects between the two merit attention: 1. failure of tumors to return to microvasculature quiescence; 2. failure of malignant cells to stop dividing; 3. failure of tumor cells to re-enter the circulation after returning to a non-activated phenotype. Analysis of these contrasting aspects leads to the reviewing of unexpected roles of immune cells in the tumor environment, recent work on ferroportin expression with lack of iron export by tumor cells, iron export by M2 macrophages, and deficient dendritic cells (DCs) in the tumor environment. DCs in lymph nodes have recently been found to bring lymph node vasculature to quiescence after antigen stimulation. Contrary to current dogma, the evidence is that some immune system cells in the tumor environment may be favoring regulators instead of diminishing tumor growth. In addition, recent data herein reviewed will make it difficult not to consider iron and iron gene expression as relevant components of the tumor environment. Finally, I conclude with wondering how much longer what I call the 'Hunter Paradigm' will dominate cancer research and immunology and how timely it is to acknowledge in the first decade of a new century, Mina Bissell as a pioneer in the change of that paradigm in Cancer Research. "Suppose he'd listened to the erudite committee; He would have only found where not to look" WH Auden.

The Siderocalin/Enterobactin Interaction: A Link between Mammalian Immunity and Bacterial Iron Transport

Energy Technology Data Exchange (ETDEWEB)

Meux, Susan C.

2008-05-12

The siderophore enterobactin (Ent) is produced by enteric bacteria to mediate iron uptake. Ent scavenges iron and is taken up by the bacteria as the highly stable ferric complex [Fe{sup III}(Ent)]{sup 3-}. This complex is also a specific target of the mammalian innate immune system protein, Siderocalin (Scn), which acts as an anti-bacterial agent by specifically sequestering siderophores and their ferric complexes during infection. Recent literature suggesting that Scn may also be involved in cellular iron transport has increased the importance of understanding the mechanism of siderophore interception and clearance by Scn; Scn is observed to release iron in acidic endosomes and [Fe{sup III}(Ent)]{sup 3-} is known to undergo a change from catecholate to salicylate coordination in acidic conditions, which is predicted to be sterically incompatible with the Scn binding pocket (also referred to as the calyx). To investigate the interactions between the ferric Ent complex and Scn at different pH values, two recombinant forms of Scn with mutations in three residues lining the calyx were prepared: Scn-W79A/R81A and Scn-Y106F. Binding studies and crystal structures of the Scn-W79A/R81A:[Fe{sup III}(Ent)]{sup 3-} and Scn-Y106F:[Fe{sup III}(Ent)]{sup 3-} complexes confirm that such mutations do not affect the overall conformation of the protein but do weaken significantly its affinity for [Fe{sup III}(Ent)]{sup 3-}. Fluorescence, UV-Vis and EXAFS spectroscopies were used to determine Scn/siderophore dissociation constants and to characterize the coordination mode of iron over a wide pH range, in the presence of both mutant proteins and synthetic salicylate analogs of Ent. While Scn binding hinders salicylate coordination transformation, strong acidification results in the release of iron and degraded siderophore. Iron release may therefore result from a combination of Ent degradation and coordination change.

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...

High-rate behaviour of iron ore pellet

Science.gov (United States)

Gustafsson, Gustaf; Häggblad, Hans-Åke; Jonsén, Pär; Nishida, Masahiro

2015-09-01

Iron ore pellets are sintered, centimetre-sized spheres of ore with high iron content. Together with carbonized coal, iron ore pellets are used in the production of steel. In the transportation from the pelletizing plants to the customers, the iron ore pellets are exposed to different loading situations, resulting in degradation of strength and in some cases fragmentation. For future reliable numerical simulations of the handling and transportation of iron ore pellets, knowledge about their mechanical properties is needed. This paper describes the experimental work to investigate the dynamic mechanical properties of blast furnace iron ore pellets. To study the dynamic fracture of iron ore pellets a number of split Hopkinson pressure bar tests are carried out and analysed.

Expression and cellular localization of hepcidin mRNA and protein in normal rat brain

Czech Academy of Sciences Publication Activity Database

Raha-Chowdhury, R.; Raha, A.A.; Forostyak, Serhiy; Zhao, J.W.; Stott, S.R.W.; Bomford, A.

2015-01-01

Roč. 16, APR 21 (2015), s. 24 ISSN 1471-2202 Institutional support: RVO:68378041 Keywords : hepcidin * ferroportin * defensin * inflammatory cytokines * brain iron homeostasis * blood brain barrier * pericytes * sub-ventricular zone * neurogenesis Subject RIV: FH - Neurology Impact factor: 2.304, year: 2015

Evaluation of iron transport from ferrous glycinate liposomes using ...

African Journals Online (AJOL)

2017-09-03

Sep 3, 2017 ... Insufficient dietary intake and low iron bio- availability in foods ... pared with common iron supplements, iron liposomes can obviously ... to inhibit iron absorption in humans and in cell culture models11. ..... ical nutrition issues. The effects of .... of approximately 2-100 nm could play an active role in mediating ...

Epigallocatechin Gallate Has a Neurorescue Effect in a Mouse Model of Parkinson Disease.

Science.gov (United States)

Xu, Qi; Langley, Monica; Kanthasamy, Anumantha G; Reddy, Manju B

2017-10-01

Background: Parkinson disease (PD) is a neurodegenerative disorder that has been associated with many factors, including oxidative stress, inflammation, and iron accumulation. The antioxidant, anti-inflammatory, and iron-chelating properties of epigallocatechin gallate (EGCG), a major polyphenol in green tea, may offer protection against PD. Objective: We sought to determine the neurorescue effects of EGCG and the role of iron in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Methods: We evaluated the neurorescue effect of EGCG (25 mg/kg, 7 d, oral administration) against MPTP-induced (20 mg/kg, 3 d, intraperitoneal injection) neurodegeneration in C57 male black mice. Thirty mice weighing ∼25 g were divided into 3 groups: control, MPTP, and MPTP + EGCG. The neurorescue effect of EGCG was assessed with the use of motor behavior tests, neurotransmitter analysis, oxidative stress indicators, and iron-related protein expression. Results: Compared with the control group, MPTP treatment shortened the mice's latency to fall from the rotarod by 16% ( P < 0.05), decreased the striatal dopamine concentration by 58% ( P < 0.001) and dihydroxyphenylacetic acid by 35% ( P < 0.05), and increased serum protein carbonyls by 71% ( P = 0.07). However, EGCG rescued MPTP-induced neurotoxicity by increasing the rotational latency by 17% ( P < 0.05) to a value similar to the control group. Striatal dopamine concentrations were 40% higher in the MPTP + EGCG group than in the MPTP group ( P < 0.05), but the values were significantly lower than in the control group. Compared with the MPTP and control groups, mice in the MPTP + EGCG group had higher substantia nigra ferroportin expression (44% and 35%, respectively) ( P < 0.05) but not hepcidin and divalent metal transporter 1 expression. Conclusion: Overall, our study demonstrated that EGCG regulated the iron-export protein ferroportin in substantia nigra, reduced oxidative stress, and exerted a neurorescue effect

ASME codification of ductile cast iron cask for transport and storage of spent nuclear fuel

International Nuclear Information System (INIS)

Saegusa, Toshiari; Arai, Taku

2012-01-01

The CRIEPI has been executing research and development on ductile cast iron cask for transport and storage of spent nuclear fuel in order to diversify options of the casks. Based on the research results, the CRIEPI proposed materials standards (Section II) and structural design standards (Section III) for the ductile cast iron cask to the authoritative and international ASME (American Society of Mechanical Engineers) Codes. For the Section II, the CRIEPI proposed the JIS G 5504 material with additional requirement prohibiting repair of cast body by welding, etc. as well as the ASTM A874 material to the Part A. In addition, the CRIEPI proposed design stress allowables, physical properties (thermal conductivity, modulus of elasticity, etc.), and external pressure chart to the Part D. For the Section III, the CRIEPI proposed a fracture toughness requirement of the ductile cast iron cask at -40degC to WB and WC of Division 3. Additionally, the CRIEPI proposed a design fatigue curve of the ductile cast iron cask to Appendix of Division 1. This report describes the outline of the proposed standards, their bases, and the deliberation process in order to promote proper usage of the code, future improvement, etc. (author)

Nicotianamine synthase overexpression positively modulates iron homeostasis-related genes in high iron rice

Directory of Open Access Journals (Sweden)

Meng eWang

2013-05-01

Full Text Available Nearly one-third of the world population, mostly women and children, suffer from iron malnutrition and its consequences, such as anemia or impaired mental development. Biofortification of rice, which is a staple crop for nearly half of the world’s population, can significantly contribute in alleviating iron deficiency. NFP rice (transgenic rice expressing nicotianamine synthase, ferritin and phytase genes has a more than six-fold increase in iron content in polished rice grains, resulting from the synergistic action of nicotianamine synthase (NAS and ferritin transgenes. We investigated iron homeostasis in NFP plants by analyzing the expression of 28 endogenous rice genes known to be involved in the homeostasis of iron and other metals, in iron-deficient and iron-sufficient conditions. RNA was collected from different tissues (roots, flag leaves, grains and at three developmental stages during grain filling. NFP plants showed increased sensitivity to iron-deficiency conditions and changes in the expression of endogenous genes involved in nicotianamine (NA metabolism, in comparison to their non-transgenic siblings. Elevated transcript levels were detected in NFP plants for several iron transporters. In contrast, expression of OsYSL2, which encodes a member of Yellow Stripe-like protein family, and a transporter of the NA-Fe(II complex was reduced in NFP plants under low iron conditions, indicating that expression of OsYSL2 is regulated by the endogenous iron status. Expression of the transgenes did not significantly affect overall iron homeostasis in NFP plants, which establishes the engineered push-pull mechanism as a suitable strategy to increase rice endosperm iron content.

Arabidopsis copper transport protein COPT2 participates in the cross talk between iron deficiency responses and low-phosphate signaling.

Science.gov (United States)

Perea-García, Ana; Garcia-Molina, Antoni; Andrés-Colás, Nuria; Vera-Sirera, Francisco; Pérez-Amador, Miguel A; Puig, Sergi; Peñarrubia, Lola

2013-05-01

Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes, including respiration, photosynthesis, and oxidative stress protection. In many eukaryotic organisms, including yeast (Saccharomyces cerevisiae) and mammals, copper and iron homeostases are highly interconnected; yet, such interdependence is not well established in higher plants. Here, we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis (Arabidopsis thaliana). COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 could play a dual role under iron deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation, possibly to minimize further iron consumption. Second, global expression analyses of copt2-1 versus wild-type Arabidopsis plants indicate that low-phosphate responses increase in the mutant. These results open up new biotechnological approaches to fight iron deficiency in crops.

Modeling of neutron and photon transport in iron and concrete radiation shields by using Monte Carlo method

CERN Document Server

Žukauskaitėa, A; Plukienė, R; Ridikas, D

2007-01-01

Particle accelerators and other high energy facilities produce penetrating ionizing radiation (neutrons and γ-rays) that must be shielded. The objective of this work was to model photon and neutron transport in various materials, usually used as shielding, such as concrete, iron or graphite. Monte Carlo method allows obtaining answers by simulating individual particles and recording some aspects of their average behavior. In this work several nuclear experiments were modeled: AVF 65 (AVF cyclotron of Research Center of Nuclear Physics, Osaka University, Japan) – γ-ray beams (1-10 MeV), HIMAC (heavy-ion synchrotron of the National Institute of Radiological Sciences in Chiba, Japan) and ISIS-800 (ISIS intensive spallation neutron source facility of the Rutherford Appleton laboratory, UK) – high energy neutron (20-800 MeV) transport in iron and concrete. The calculation results were then compared with experimental data.compared with experimental data.

Structure of the nucleotide-binding domain of a dipeptide ABC transporter reveals a novel iron-sulfur cluster-binding domain.

Science.gov (United States)

Li, Xiaolu; Zhuo, Wei; Yu, Jie; Ge, Jingpeng; Gu, Jinke; Feng, Yue; Yang, Maojun; Wang, Linfang; Wang, Na

2013-02-01

Dipeptide permease (Dpp), which belongs to an ABC transport system, imports peptides consisting of two or three L-amino acids from the matrix to the cytoplasm in microbes. Previous studies have indicated that haem competes with dipeptides to bind DppA in vitro and in vivo and that the Dpp system can also translocate haem. Here, the crystal structure of DppD, the nucleotide-binding domain (NBD) of the ABC-type dipeptide/oligopeptide/nickel-transport system from Thermoanaerobacter tengcongensis, bound with ATP, Mg(2+) and a [4Fe-4S] iron-sulfur cluster is reported. The N-terminal domain of DppD shares a similar structural fold with the NBDs of other ABC transporters. Interestingly, the C-terminal domain of DppD contains a [4Fe-4S] cluster. The UV-visible absorbance spectrum of DppD was consistent with the presence of a [4Fe-4S] cluster. A search with DALI revealed that the [4Fe-4S] cluster-binding domain is a novel structural fold. Structural analysis and comparisons with other ABC transporters revealed that this iron-sulfur cluster may act as a mediator in substrate (dipeptide or haem) binding by electron transfer and may regulate the transport process in Dpp ABC transport systems. The crystal structure provides a basis for understanding the properties of ABC transporters and will be helpful in investigating the functions of NBDs in the regulation of ABC transporter activity.

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

Science.gov (United States)

Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

Hydrogen transport in iron and steel

International Nuclear Information System (INIS)

Louthan, M.R. Jr.; Derrick, R.G.; Donovan, J.A.; Caskey, G.R. Jr.

1975-01-01

The permeabilities of protium, deuterium, and tritium in iron and T-1 steel at temperatures as low as 260 0 K are in agreement with the equation proposed by Gonzalez. However, the permeabilities of HP-9-4-20 and 4130 steel to hydrogen are typically lower than predicted. The present data also show that, within experimental accuracy, the isotope effect on the permeability of hydrogen in HP-9-4-20, 4130 and T-1 steel, and high purity iron can be estimated by an inverse square root of mass correction. Trapping effects prevent the development of diffusivity and solubility equations. (auth)

The solubility of iron sulfides and their role in mass transport in Girdler-Sulfide heavy water plants

International Nuclear Information System (INIS)

Tewari, P.H.; Wallace, G.; Campbell, A.B.

1978-04-01

The solubilities of several iron sulfides, mackinawite FeSsub((1-x)), troilite FeS, pyrrhotite Fesub((1-x))S (monoclinic and hexagonal), and pyrite FeS 2 have been determined in aqueous H 2 S solution at 0.1 MPa and 1.8 MPa H 2 S pressures between 25 deg and 125 deg C. The dependence of solubility on the pH of the medium has also been studied. It is concluded that since mackinawite is the most soluble of the iron sulfides, and has the highest dissolution rate and the steepest decline in solubility with temperature, its prolonged formation during plant operation should be avoided to minimize iron transport from lower to higher temperature areas in Girdler-Sulfide (G.S.) heavy water plants. This can be achieved by a preconditioning of carbon steel surfaces to convert mackinawite to pyrrhotite and pyrite

Iron deficiency in childhood

NARCIS (Netherlands)

Uijterschout, L.

2015-01-01

Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

Science.gov (United States)

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

SQCRAMscope imaging of transport in an iron-pnictide superconductor

Science.gov (United States)

Yang, Fan; Kollar, Alicia; Taylor, Stephen; Palmstrom, Johanna; Chu, Jiun-Haw; Fisher, Ian; Lev, Benjamin

2017-04-01

Microscopic imaging of local magnetic fields provides a window into the organizing principles of complex and technologically relevant condensed matter materials. However, a wide variety of intriguing strongly correlated and topologically nontrivial materials exhibit poorly understood phenomena outside the detection capability of state-of-the-art high-sensitivity, high-resolution scanning probe magnetometers. We have recently introduced a quantum-noise-limited scanning probe magnetometer that can operate from room-to-cryogenic temperatures with unprecedented DC-field sensitivity and micron-scale resolution. The Scanning Quantum Cryogenic Atom Microscope (SQCRAMscope) employs a magnetically levitated atomic Bose-Einstein condensate (BEC), thereby providing immunity to conductive and blackbody radiative heating. We will report on the first use of the SQCRAMscope for imaging a strongly correlated material. Specifically, we will present measurements of electron transport in iron-pnictide superconductors across the electron nematic phase transition at T = 135 K.

Impact of Subsurface Heterogeneities on nano-Scale Zero Valent Iron Transport

Science.gov (United States)

Krol, M. M.; Sleep, B. E.; O'Carroll, D. M.

2011-12-01

Nano-scale zero valent iron (nZVI) has been applied as a remediation technology at sites contaminated with chlorinated compounds and heavy metals. Although laboratory studies have demonstrated high reactivity for the degradation of target contaminants, the success of nZVI in the field has been limited due to poor subsurface mobility. When injected into the subsurface, nZVI tends to aggregate and be retained by subsurface soils. As such nZVI suspensions need to be stabilized for increased mobility. However, even with stabilization, soil heterogeneities can still lead to non-uniform nZVI transport, resulting in poor distribution and consequently decreased degradation of target compounds. Understanding how nZVI transport can be affected by subsurface heterogeneities can aid in improving the technology. This can be done with the use of a numerical model which can simulate nZVI transport. In this study CompSim, a finite difference groundwater model, is used to simulate the movement of nZVI in a two-dimensional domain. CompSim has been shown in previous studies to accurately predict nZVI movement in the subsurface, and is used in this study to examine the impact of soil heterogeneity on nZVI transport. This work also explores the impact of different viscosities of the injected nZVI suspensions (corresponding to different stabilizing polymers) and injection rates on nZVI mobility. Analysis metrics include travel time, travel distance, and average nZVI concentrations. Improving our understanding of the influence of soil heterogeneity on nZVI transport will lead to improved field scale implementation and, potentially, to more effective remediation of contaminated sites.

Effects of acute dietary iron overload in pigs (Sus scrofa) with induced type 2 diabetes mellitus.

Science.gov (United States)

Espinoza, A; Morales, S; Arredondo, M

2014-06-01

Epidemiological studies have reported an association between high iron (Fe) levels and elevated risk of developing type 2 diabetes mellitus (T2D). It is believed that the formation of Fe-catalyzed hydroxyl radicals may contribute to the development of diabetes. Our goal was to determine the effect of a diet with a high Fe content on type 2 diabetic pigs. Four groups of piglets were studied: (1) control group, basal diet; (2) Fe group, basal diet with 3,000 ppm ferrous sulfate; (3) diabetic group (streptozotocin-induced type 2 diabetes) with basal diet; (4) diabetic/Fe group, diabetic animals/3,000 ppm ferrous sulfate. For 2 months, biochemical and hematological parameters were evaluated. Tissue samples of liver and duodenum were obtained to determine mRNA relative abundance of DMT1, ferroportin (Fpn), ferritin (Fn), hepcidin (Hpc), and transferrin receptor by qRT-PCR. Fe group presented increased levels of hematological (erythrocytes, hematocrit, and hemoglobin) and iron parameters. Diabetic/Fe group showed similar behavior as Fe group but in lesser extent. The relative abundance of different genes in the four study groups yielded a different expression pattern. DMT1 showed a lower expression in the two iron groups compared with control and diabetic animals, and Hpc showed an increased on its expression in Fe and diabetic/Fe groups. Diabetic/Fe group presents greater expression of Fn and Fpn. These results suggest that there is an interaction between Fe nutrition, inflammation, and oxidative stress in the diabetes development.

Application of a discrete-energy, discrete-ordinates technique to the study of neutron transport in iron

International Nuclear Information System (INIS)

Ching, J.T.

1975-01-01

An algebraic equivalence between the point-energy and multigroup forms of the Boltzmann transport equation is demonstrated which allows the development of a discrete-energy, discrete-ordinates method for the solution of radiation transport problems. The method utilizes a modified version of a cross section processing scheme devised for the moments method code BMT and the transport equation solution algorithm from the one-dimensional discrete-ordinates transport code ANISN. The combined system, identified as MOMANS, computes fluxes directly from point cross sections in a single operation. In the cross-section processing, the group averaging required for multigroup calculations is replaced by a fast numerical scheme capable of generating a set of transfer cross sections containing all the physical features of interest, thereby increasing the detail in the calculated results. Test calculations in which the discrete-energy method was compared with the multigroup method have shown that for the same energy grid (number of points = number of groups), the discrete-energy method is faster but somewhat less accurate than the multigroup method. However, the accuracy of the discrete-energy method increases rapidly as the spacing between energy points is decreased, approaching that of multigroup calculations. For problems requiring great detail in the energy spectrum the discrete-energy method has therefore proven to be as accurate as, and more economical than, the multigroup technique. This was demonstrated by the application of the method to the study of the transport of neutrons in an iron sphere. Using the capability of the discrete-energy method for rapidly treating changes in cross-section sets, the propagation of neutrons from a 14 MeV source in a 22 cm radius sphere of iron was analyzed for sensitivity to changes in the microscopic scattering mechanisms

Abscisic acid alleviates iron deficiency by promoting root iron reutilization and transport from root to shoot in Arabidopsis.

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Lei, Gui Jie; Zhu, Xiao Fang; Wang, Zhi Wei; Dong, Fang; Dong, Ning Yu; Zheng, Shao Jian

2014-04-01

Abscisic acid (ABA) has been demonstrated to be involved in iron (Fe) homeostasis, but the underlying mechanism is largely unknown. Here, we found that Fe deficiency induced ABA accumulation rapidly (within 6 h) in the roots of Arabidopsis. Exogenous ABA at 0.5 μM decreased the amount of root apoplastic Fe bound to pectin and hemicellulose, and increased the shoot Fe content significantly, thus alleviating Fe deficiency-induced chlorosis. Exogenous ABA promoted the secretion of phenolics to release apoplastic Fe and up-regulated the expression of AtNRAMP3 to enhance reutilization of Fe stored in the vacuoles, leading to a higher level of soluble Fe and lower ferric-chelate reductase (FCR) activity in roots. Treatment with ABA also led to increased Fe concentrations in the xylem sap, partially because of the up-regulation of AtFRD3, AtYSL2 and AtNAS1, genes related to long-distance transport of Fe. Exogenous ABA could not alleviate the chlorosis of abi5 mutant resulting from the significantly low expression of AtYSL2 and low transport of Fe from root to shoot. Taken together, our data support the conclusion that ABA is involved in the reutilization and transport of Fe from root to shoot under Fe deficiency conditions in Arabidopsis. © 2013 John Wiley & Sons Ltd.

Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake

Science.gov (United States)

2016-01-01

Mycobacterium tuberculosis requires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe3+-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival of M. tuberculosis, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrophages. But as excess iron is toxic due to its catalytic role in the generation of free radicals, regulation of iron uptake is necessary to maintain optimal levels of intracellular iron. The focus of this review is to present a comprehensive overview of iron homeostasis in M. tuberculosis that is discussed in the context of mycobactin biosynthesis, transport of iron across the mycobacterial cell envelope, and storage of excess iron. The clinical significance of the serum iron status and the expression of the iron-regulated protein HupB in tuberculosis (TB) patients is presented here, highlighting the potential of HupB as a marker, notably in extrapulmonary TB cases. PMID:27402628

Dinitrosyl iron complexes and S-nitrosothiols are two possible forms for stabilization and transport of nitric oxide in biological systems.

Science.gov (United States)

Vanin, A F

1998-07-01

The physicochemical properties, mechanisms of synthesis and decomposition of dinitrosyl iron complexes (DNICs) with thiol-containing ligands and of S-nitrosothiols (RS-NO), and the potential role of these compounds in storage and transport of NO in biological systems are reviewed. Special attention is given to the phenomenon of mutual transformation of DNIC and RS-NO catalyzed by Fe2+. Each Fe2+ binds two neutral NO molecules in the DNICs, catalyzes their mutual oxidation--reduction with formation of nitrous oxide and nitrosonium ions appearing in the DNICs. These ions S-nitrosate thiol-compounds with RS-NO formation. Fe2+ binds two RS-NO molecules and catalyzes their mutual oxidation--reduction followed by decomposition of the resulting molecules. Mutual conversion of DNICs and RS-NO regulated by iron, thiol, and NO levels is suggested to provide NO transport in cells and tissues.

Planar Perovskite Solar Cells with High Open-Circuit Voltage Containing a Supramolecular Iron Complex as Hole Transport Material Dopant.

Science.gov (United States)

Saygili, Yasemin; Turren-Cruz, Silver-Hamill; Olthof, Selina; Saes, Bartholomeus Wilhelmus Henricus; Pehlivan, Ilknur Bayrak; Saliba, Michael; Meerholz, Klaus; Edvinsson, Tomas; Zakeeruddin, Shaik M; Grätzel, Michael; Correa-Baena, Juan-Pablo; Hagfeldt, Anders; Freitag, Marina; Tress, Wolfgang

2018-04-26

In perovskite solar cells (PSCs), the most commonly used hole transport material (HTM) is spiro-OMeTAD, which is typically doped by metalorganic complexes, for example, based on Co, to improve charge transport properties and thereby enhance the photovoltaic performance of the device. In this study, we report a new hemicage-structured iron complex, 1,3,5-tris(5'-methyl-2,2'-bipyridin-5-yl)ethylbenzene Fe(III)-tris(bis(trifluoromethylsulfonyl)imide), as a p-type dopant for spiro-OMeTAD. The formal redox potential of this compound was measured as 1.29 V vs. the standard hydrogen electrode, which is slightly (20 mV) more positive than that of the commercial cobalt dopant FK209. Photoelectron spectroscopy measurements confirm that the iron complex acts as an efficient p-dopant, as evidenced in an increase of the spiro-OMeTAD work function. When fabricating planar PSCs with the HTM spiro-OMeTAD doped by 5 mol % of the iron complex, a power conversion efficiency of 19.5 % (AM 1.5G, 100 mW cm -2 ) is achieved, compared to 19.3 % for reference devices with FK209. Open circuit voltages exceeding 1.2 V at 1 sun and reaching 1.27 V at 3 suns indicate that recombination at the perovskite/HTM interface is low when employing this iron complex. This work contributes to recent endeavors to reduce recombination losses in perovskite solar cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Siderophore-mediated iron trafficking in humans is regulated by iron

Science.gov (United States)

Liu, Zhuoming; Lanford, Robert; Mueller, Sebastian; Gerhard, Glenn S.; Luscieti, Sara; Sanchez, Mayka; Devireddy, L.

2013-01-01

Siderophores are best known as small iron binding molecules that facilitate microbial iron transport. In our previous study we identified a siderophore-like molecule in mammalian cells and found that its biogenesis is evolutionarily conserved. A member of the short chain dehydrogenase family of reductases, 3-OH butyrate dehydrogenase (BDH2) catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore. We have shown that depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of cellular iron and mitochondrial iron deficiency. These observations suggest that the mammalian siderophore is a critical regulator of cellular iron homeostasis and facilitates mitochondrial iron import. By utilizing bioinformatics, we identified an iron-responsive element (IRE; a stem-loop structure that regulates genes expression post-transcriptionally upon binding to iron regulatory proteins or IRPs) in the 3′-untranslated region (3′-UTR) of the human BDH2 (hBDH2) gene. In cultured cells as well as in patient samples we now demonstrate that the IRE confers iron-dependent regulation on hBDH2 and binds IRPs in RNA electrophoretic mobility shift assays. In addition, we show that the hBDH2 IRE associates with IRPs in cells and that abrogation of IRPs by RNAi eliminates the iron-dependent regulation of hBDH2 mRNA. The key physiologic implication is that iron-mediated post-transcriptional regulation of hBDH2 controls mitochondrial iron homeostasis in human cells. These observations provide a new and an unanticipated mechanism by which iron regulates its intracellular trafficking. PMID:22527885

Metagenomic Study of Iron Homeostasis in Iron Depositing Hot Spring Cyanobacterial Community

Science.gov (United States)

Brown, I.; Franklin H.; Tringe, S. G.; Klatt, C. G.; Bryant, D. A.; Sarkisova, S. A.; Guevara, M.

2010-01-01

Introduction: It is not clear how an iron-rich thermal hydrosphere could be hospitable to cyanobacteria, since reduced iron appears to stimulate oxidative stress in all domains of life and particularly in oxygenic phototrophs. Therefore, metagenomic study of cyanobacterial community in iron-depositing hot springs may help elucidate how oxygenic prokaryotes can withstand the extremely high concentrations of reactive oxygen species (ROS) produced by interaction between environmental Fe2+ and O2. Method: Anchor proteins from various species of cyanobacteria and some anoxygenic phototrophs were selected on the basis of their hypothetical role in Fe homeostasis and the suppression of oxidative stress and were BLASTed against the metagenomes of iron-depositing Chocolate Pots and freshwater Mushroom hot springs. Results: BLASTing proteins hypothesized to be involved in Fe homeostasis against the microbiomes from the two springs revealed that iron-depositing hot spring has a greater abundance of defensive proteins such as bacterioferritin comigratory protein (Bcp) and DNA-binding Ferritin like protein (Dps) than a fresh-water hot spring. One may speculate that the abundance of Bcp and Dps in an iron-depositing hot spring is connected to the need to suppress oxidative stress in bacteria inhabiting environments with high Fe2+ concnetration. In both springs, Bcp and Dps are concentrated within the cyanobacterial fractions of the microbial community (regardless of abundance). Fe3+ siderophore transport (from the transport system permease protein query) may be less essential to the microbial community of CP because of the high [Fe]. Conclusion: Further research is needed to confirm that these proteins are unique to photoautotrophs such as those living in iron-depositing hot spring.

The effect of wheat prebiotics on the gut bacterial population and iron status of iron deficient broiler chickens.

Science.gov (United States)

Tako, Elad; Glahn, Raymond P; Knez, Marija; Stangoulis, James Cr

2014-06-13

Currently, there is a lot of interest in improving gut health, and consequently increasing Fe absorption, by managing the colonic microbial population. This is traditionally done by the consumption of probiotics, live microbial food supplements. However, an alternative, and often very effective approach, is the consumption of food ingredients known as prebiotics. Fructans and arabinoxylans are naturally occurring non-digestible oligosaccharides in wheat that exhibit prebiotic properties and may enhance intestinal iron (Fe) absorption. The aim of this study was to assess the effect of prebiotics from wheat on Fe bioavailability in vitro (Caco-2 cells) and in vivo (broiler chickens, Gallus gallus). In the current study, the effect of intra-amniotic administration of wheat samples extracts at 17 d of embryonic incubation on the Fe status and possible changes in the bacterial population in intestinal content of broiler hatchlings were investigated. A group of 144 eggs were injected with the specified solution (1 ml per egg) into the amniotic fluid. Immediately after hatch (21 d) and from each treatment group, 10 chicks were euthanized and their small intestine, liver and cecum were removed for relative mRNA abundance of intestinal Fe related transporters, relative liver ferritin amounts and bacterial analysis of cecal content, respectively. The in vivo results are in agreement with the in vitro observations, showing no differences in the hatchling Fe status between the treatment groups, as Fe bioavailability was not increased in vitro and no significant differences were measured in the intestinal expression of DMT1, Ferroportin and DcytB in vivo. However, there was significant variation in relative amounts of bifidobacteria and lactobacilli in the intestinal content between the treatments groups, with generally more bifidobacteria being produced with increased prebiotic content. In this study we showed that prebiotics naturally found in wheat grains/bread products

Staphylococcus aureus redirects central metabolism to increase iron availability.

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David B Friedman

2006-08-01

Full Text Available Staphylococcus aureus pathogenesis is significantly influenced by the iron status of the host. However, the regulatory impact of host iron sources on S. aureus gene expression remains unknown. In this study, we combine multivariable difference gel electrophoresis and mass spectrometry with multivariate statistical analyses to systematically cluster cellular protein response across distinct iron-exposure conditions. Quadruplicate samples were simultaneously analyzed for alterations in protein abundance and/or post-translational modification state in response to environmental (iron chelation, hemin treatment or genetic (Deltafur alterations in bacterial iron exposure. We identified 120 proteins representing several coordinated biochemical pathways that are affected by changes in iron-exposure status. Highlighted in these experiments is the identification of the heme-regulated transport system (HrtAB, a novel transport system which plays a critical role in staphylococcal heme metabolism. Further, we show that regulated overproduction of acidic end-products brought on by iron starvation decreases local pH resulting in the release of iron from the host iron-sequestering protein transferrin. These findings reveal novel strategies used by S. aureus to acquire scarce nutrients in the hostile host environment and begin to define the iron and heme-dependent regulons of S. aureus.

Zinc transporter ZIP14 functions in hepatic zinc, iron and glucose homeostasis during the innate immune response (endotoxemia.

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Tolunay Beker Aydemir

Full Text Available ZIP14 (slc39A14 is a zinc transporter induced in response to pro-inflammatory stimuli. ZIP14 induction accompanies the reduction in serum zinc (hypozincemia of acute inflammation. ZIP14 can transport Zn(2+ and non-transferrin-bound Fe(2+ in vitro. Using a Zip14(-/- mouse model we demonstrated that ZIP14 was essential for control of phosphatase PTP1B activity and phosphorylation of c-Met during liver regeneration. In the current studies, a global screening of ZIP transporter gene expression in response to LPS-induced endotoxemia was conducted. Following LPS, Zip14 was the most highly up-regulated Zip transcript in liver, but also in white adipose tissue and muscle. Using ZIP14(-/- mice we show that ZIP14 contributes to zinc absorption from the gastrointestinal tract directly or indirectly as zinc absorption was decreased in the KOs. In contrast, Zip14(-/- mice absorbed more iron. The Zip14 KO mice did not exhibit hypozincemia following LPS, but do have hypoferremia. Livers of Zip14-/- mice had increased transcript abundance for hepcidin, divalent metal transporter-1, ferritin and transferrin receptor-1 and greater accumulation of iron. The Zip14(-/- phenotype included greater body fat, hypoglycemia and higher insulin levels, as well as increased liver glucose and greater phosphorylation of the insulin receptor and increased GLUT2, SREBP-1c and FASN expression. The Zip14 KO mice exhibited decreased circulating IL-6 with increased hepatic SOCS-3 following LPS, suggesting SOCS-3 inhibited insulin signaling which produced the hypoglycemia in this genotype. The results are consistent with ZIP14 ablation yielding abnormal labile zinc pools which lead to increased SOCS-3 production through G-coupled receptor activation and increased cAMP production as well as signaled by increased pSTAT3 via the IL-6 receptor, which inhibits IRS 1/2 phosphorylation. Our data show the role of ZIP14 in the hepatocyte is multi-functional since zinc and iron trafficking are

Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure.

Science.gov (United States)

Ye, Qi; Kim, Jonghan

2016-06-01

Increased accumulation of manganese (Mn) in the brain is significantly associated with neurobehavioral deficits and impaired brain function. Airborne Mn has a high systemic bioavailability and can be directly taken up into the brain, making it highly neurotoxic. While Mn transport is in part mediated by several iron transporters, the expression of these transporters is altered by the iron regulatory gene, HFE. Mutations in the HFE gene are the major cause of the iron overload disorder, hereditary hemochromatosis, one of the prevalent genetic diseases in humans. However, whether or not HFE mutation modifies Mn-induced neurotoxicity has not been evaluated. Therefore, our goal was to define the role of HFE mutation in Mn deposition in the brain and the resultant neurotoxic effects after olfactory Mn exposure. Mice carrying the H67D HFE mutation, which is homologous to the H63D mutation in humans, and their control, wild-type mice, were intranasally instilled with MnCl2 with different doses (0, 0.2, 1.0 and 5.0 mg kg(-1)) daily for 3 days. Mn levels in the blood, liver and brain were determined using inductively-coupled plasma mass spectrometry (ICP-MS). H67D mutant mice showed significantly lower Mn levels in the blood, liver, and most brain regions, especially in the striatum, while mice fed an iron-overload diet did not. Moreover, mRNA expression of ferroportin, an essential exporter of iron and Mn, was up-regulated in the striatum. In addition, the levels of isoprostane, a marker of lipid peroxidation, were increased in the striatum after Mn exposure in wild-type mice, but were unchanged in H67D mice. Together, our results suggest that the H67D mutation provides decreased susceptibility to Mn accumulation in the brain and neurotoxicity induced by inhaled Mn.

Cytotoxicity, Intestinal Transport, and Bioavailability of Dispersible Iron and Zinc Supplements

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Jae-Min Oh

2017-04-01

Full Text Available Iron or zinc deficiency is one of the most important nutritional disorders which causes health problem. However, food fortification with minerals often induces unacceptable organoleptic changes during preparation process and storage, has low bioavailability and solubility, and is expensive. Nanotechnology surface modification to obtain novel characteristics can be a useful tool to overcome these problems. In this study, the efficacy and potential toxicity of dispersible Fe or Zn supplement coated in dextrin and glycerides (SunActive FeTM and SunActive ZnTM were evaluated in terms of cytotoxicity, intestinal transport, and bioavailability, as compared with each counterpart without coating, ferric pyrophosphate (FePP and zinc oxide (ZnO nanoparticles (NPs, respectively. The results demonstrate that the cytotoxicity of FePP was not significantly affected by surface modification (SunActive FeTM, while SunActive ZnTM was more cytotoxic than ZnO-NPs. Cellular uptake and intestinal transport efficiency of SunActive FeTM were significantly higher than those of its counterpart material, which was in good agreement with enhanced oral absorption efficacy after a single-dose oral administration to rats. These results seem to be related to dissolution, particle dispersibility, and coating stability of materials depending on suspending media. Both SunActiveTM products and their counterpart materials were determined to be primarily transported by microfold (M cells through the intestinal epithelium. It was, therefore, concluded that surface modification of food fortification will be a useful strategy to enhance oral absorption efficiency at safe levels.

A program to qualify ductile cast iron for use as a containment material for type B transport cask

International Nuclear Information System (INIS)

Golliher, K.G.; Sorenson, K.B.; Witt, C.R.

1990-01-01

This paper reports on the Department of Energy (DOE) investigations for the use of ductile cast iron (DCI) as a candidate material for radioactive material transportation cask construction. The investigation will include materials testing and full-scale cask testing. The major effort will focus on materials qualification and cask evaluation of the 9 meter and puncture drop test events. Interaction by contract with the private industry, the American Society for Testing and Materials (ASTM) Committee A4.04, and the Electric Power Research Institute (EPRI) will be actively pursued to establish material specification acceptance criteria for ductile iron use as a cask material in the United States of America (USA). All test results will be documented in the safety analysis report for packaging for submission to the U.S. Nuclear Regulatory Commission (NRC). The goal of this program is a certificate of compliance for DCI from the NRC to transport high-level radioactive materials. The acceptance of DCI within the USA cask design community will offer an alternative to present-day materials for cask construction, and its entry has the potential of providing significant cost-savings

Ab initio study of spin-dependent transport in carbon nanotubes with iron and vanadium adatoms

DEFF Research Database (Denmark)

Fürst, Joachim Alexander; Brandbyge, Mads; Jauho, Antti-Pekka

2008-01-01

(majority or minority) being scattered depends on the adsorbate and is explained in terms of d-state filling. We contrast the single-walled carbon nanotube results to the simpler case of the adsorbate on a flat graphene sheet with periodic boundary conditions and corresponding width in the zigzag direction......We present an ab initio study of spin-dependent transport in armchair carbon nanotubes with transition metal adsorbates: iron or vanadium. The method based on density functional theory and nonequilibrium Green's functions is used to compute the electronic structure and zero-bias conductance...

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

Physical transformations of iron oxide and silver nanoparticles from an intermediate scale field transport study

Science.gov (United States)

Emerson, Hilary P.; Hart, Ashley E.; Baldwin, Jonathon A.; Waterhouse, Tyler C.; Kitchens, Christopher L.; Mefford, O. Thompson; Powell, Brian A.

2014-02-01

In recent years, there has been increasing concern regarding the fate and transport of engineered nanoparticles (NPs) in environmental systems and the potential impacts on human and environmental health due to the exponential increase in commercial and industrial use worldwide. To date, there have been relatively few field-scale studies or laboratory-based studies on environmentally relevant soils examining the chemical/physical behavior of the NPs following release into natural systems. The objective of this research is to demonstrate the behavior and transformations of iron oxide and silver NPs with different capping ligands within the unsaturated zone. Here, we show that NP transport within the vadose zone is minimal primarily due to heteroaggregation with soil surface coatings with results that >99 % of the NPs remained within 5 cm of the original source after 1 year in intermediate-scale field lysimeters. These results suggest that transport may be overestimated when compared to previous laboratory-scale studies on pristine soils and pure minerals and that future work must incorporate more environmentally relevant parameters.

Chloroquine Interference with Hemoglobin Endocytic Trafficking Suppresses Adaptive Heme and Iron Homeostasis in Macrophages: The Paradox of an Antimalarial Agent

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Christian A. Schaer

2013-01-01

Full Text Available The CD163 scavenger receptor pathway for Hb:Hp complexes is an essential mechanism of protection against the toxicity of extracellular hemoglobin (Hb, which can accumulate in the vasculature and within tissues during hemolysis. Chloroquine is a lysosomotropic agent, which has been extensively used as an antimalarial drug in the past, before parasite resistance started to limit its efficacy in most parts of the world. More recent use of chloroquine is related to its immunomodulatory activity in patients with autoimmune diseases, which may also involve hemolytic disease components. In this study we examined the effects of chloroquine on the human Hb clearance pathway. For this purpose we developed a new mass-spectrometry-based method to specifically quantify intracellular Hb peptides within the endosomal-lysosomal compartment by single reaction monitoring (SRM. We found that chloroquine exposure impairs trafficking of Hb:Hp complexes through the endosomal-lysosomal compartment after internalization by CD163. Relative quantification of intracellular Hb peptides by SRM confirmed that chloroquine blocked cellular Hb:Hp catabolism. This effect suppressed the cellular heme-oxygenase-1 (HO-1 response and shifted macrophage iron homeostasis towards inappropriately high expression of the transferrin receptor with concurrent inhibition of ferroportin expression. A functional deficiency of Hb detoxification and heme-iron recycling may therefore be an adverse consequence of chloroquine treatment during hemolysis.

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

Science.gov (United States)

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.

Improved mass spectrometry assay for plasma hepcidin: detection and characterization of a novel hepcidin isoform.

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Coby M M Laarakkers

Full Text Available Mass spectrometry (MS-based assays for the quantification of the iron regulatory hormone hepcidin are pivotal to discriminate between the bioactive 25-amino acid form that can effectively block the sole iron transporter ferroportin and other naturally occurring smaller isoforms without a known role in iron metabolism. Here we describe the design, validation and use of a novel stable hepcidin-25(+40 isotope as internal standard for quantification. Importantly, the relative large mass shift of 40 Da makes this isotope also suitable for easy-to-use medium resolution linear time-of-flight (TOF platforms. As expected, implementation of hepcidin-25(+40 as internal standard in our weak cation exchange (WCX TOF MS method yielded very low inter/intra run coefficients of variation. Surprisingly, however, in samples from kidney disease patients, we detected a novel peak (m/z 2673.9 with low intensity that could be identified as hepcidin-24 and had previously remained unnoticed due to peak interference with the formerly used internal standard. Using a cell-based bioassay it was shown that synthetic hepcidin-24 was, like the -22 and -20 isoforms, a significantly less potent inducer of ferroportin degradation than hepcidin-25. During prolonged storage of plasma at room temperature, we observed that a decrease in plasma hepcidin-25 was paralleled by an increase in the levels of the hepcidin-24, -22 and -20 isoforms. This provides first evidence that all determinants for the conversion of hepcidin-25 to smaller inactive isoforms are present in the circulation, which may contribute to the functional suppression of hepcidin-25, that is significantly elevated in patients with renal impairment. The present update of our hepcidin TOF MS assay together with improved insights in the source and preparation of the internal standard, and sample stability will further improve our understanding of circulating hepcidin and pave the way towards further optimization and

Sudden Sensorineural Hearing Loss and Polymorphisms in Iron Homeostasis Genes: New Insights from a Case-Control Study

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Alessandro Castiglione

2015-01-01

Full Text Available Background. Even if various pathophysiological events have been proposed as explanations, the putative cause of sudden hearing loss remains unclear. Objectives. To investigate and to reveal associations (if any between the main iron-related gene variants and idiopathic sudden sensorineural hearing loss. Study Design. Case-control study. Materials and Methods. A total of 200 sudden sensorineural hearing loss patients (median age 63.65 years; range 10–92 were compared with 400 healthy control subjects. The following genetic variants were investigated: the polymorphism c.−8CG in the promoter of the ferroportin gene (FPN1; SLC40A1, the two isoforms C1 and C2 (p.P570S of the transferrin protein (TF, the amino acidic substitutions p.H63D and p.C282Y in the hereditary hemochromatosis protein (HFE, and the polymorphism c.–582AG in the promoter of the HEPC gene, which encodes the protein hepcidin (HAMP. Results. The homozygous genotype c.−8GG of the SLC40A1 gene revealed an OR for ISSNHL risk of 4.27 (CI 95%, 2.65–6.89; P=0.001, being overrepresented among cases. Conclusions. Our study indicates that the homozygous genotype FPN1 −8GG was significantly associated with increased risk of developing sudden hearing loss. These findings suggest new research should be conducted in the field of iron homeostasis in the inner ear.

Ironing Out the Unconventional Mechanisms of Iron Acquisition and Gene Regulation in Chlamydia

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Nick D. Pokorzynski

2017-09-01

Full Text Available The obligate intracellular pathogen Chlamydia trachomatis, along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron in vitro induces an aberrant morphological phenotype termed “persistence.” This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute Chlamydia-associated chronic diseases in susceptible populations. Given the importance of iron to Chlamydia, relatively little is understood about its acquisition and its role in gene regulation in comparison to other iron-dependent bacteria. Analysis of the genome sequences of a variety of chlamydial species hinted at the involvement of unconventional mechanisms, being that Chlamydia lack many conventional systems of iron homeostasis that are highly conserved in other bacteria. Herein we detail past and current research regarding chlamydial iron biology in an attempt to provide context to the rapid progress of the field in recent years. We aim to highlight recent discoveries and innovations that illuminate the strategies involved in chlamydial iron homeostasis, including the vesicular mode of acquiring iron from the intracellular environment, and the identification of a putative iron-dependent transcriptional regulator that is synthesized as a fusion with a ABC-type transporter subunit. These recent findings, along with the noted absence of iron-related homologs, indicate that Chlamydia have evolved atypical approaches to the problem of iron homeostasis, reinvigorating research into the iron biology of this pathogen.

Role of dust alkalinity in acid mobilization of iron

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A. Ito

2010-10-01

Full Text Available Atmospheric processing of mineral aerosols by acid gases (e.g., SO₂, HNO₃, N₂O₅, and HCl may play a key role in the transformation of insoluble iron (Fe in the oxidized or ferric (III form to soluble forms (e.g., Fe(II, inorganic soluble species of Fe(III, and organic complexes of iron. On the other hand, mineral dust particles have a potential of neutralizing the acidic species due to the alkaline buffer ability of carbonate minerals (e.g., CaCO₃ and MgCO₃. Here we demonstrate the impact of dust alkalinity on the acid mobilization of iron in a three-dimensional aerosol chemistry transport model that includes a mineral dissolution scheme. In our model simulations, most of the alkaline dust minerals cannot be entirely consumed by inorganic acids during the transport across the North Pacific Ocean. As a result, the inclusion of alkaline compounds in aqueous chemistry substantially limits the iron dissolution during the long-range transport to the North Pacific Ocean: only a small fraction of iron (<0.2% dissolves from hematite in the coarse-mode dust aerosols with 0.45% soluble iron initially. On the other hand, a significant fraction of iron (1–2% dissolves in the fine-mode dust aerosols due to the acid mobilization of the iron-containing minerals externally mixed with carbonate minerals. Consequently, the model quantitatively reproduces higher iron solubility in smaller particles as suggested by measurements over the Pacific Ocean. It implies that the buffering effect of alkaline content in dust aerosols might help to explain the inverse relationship between aerosol iron solubility and particle size. We also demonstrate that the iron solubility is sensitive to the chemical specification of iron-containing minerals in dust. Compared with the dust sources, soluble iron from combustion sources contributes to a relatively marginal effect for deposition of soluble iron over the North

Hydrogen and deuterium trapping in iron

Energy Technology Data Exchange (ETDEWEB)

Johnson, H H; Lin, R W

1981-02-01

The research described is directed at present almost exclusively to hydrogen transport, including both chemical and physical trapping, in iron and iron-base alloys. Some attention is directed to isotope effects. Efforts are made to clarify and understand hydrogen-related phenomena which are believed to be of direct importance to practical performance.

EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

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Dan Chen

2015-01-01

Full Text Available Background. Parkinson’s disease (PD is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−-epigallocatechin-3-gallate (EGCG against 6-hydroxydopamine- (6-OHDA- induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05 increased divalent metal transporter-1 (DMT1 and hepcidin and decreased ferroportin 1 (Fpn1 level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, p<0.01 cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05, supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001 TH+ cell count (~3-fold and neurite length (~12-fold compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.

Iron and zinc complexation in wild-type and ferritin-expressing wheat grain: implications for mineral transport into developing grain

DEFF Research Database (Denmark)

Neal, Andrew L; Geraki, Kalotina; Borg, Søren

2013-01-01

of modified complexation of both metals in transgenic grain overexpressing wheat ferritin. For zinc, there is a consistent doubling of the number of complexing phosphorus atoms. Although there is some EXAFS evidence for iron phytate in ferritin-expressing grain, there is also evidence of a structure lacking......We have used synchrotron-based X-ray fluorescence and absorption techniques to establish both metal distribution and complexation in mature wheat grains. In planta, extended X-ray absorption fine structure (EXAFS) spectroscopy reveals iron phytate and zinc phytate structures in aleurone cells...... of ferritin-expressing grains is quite different from that in wild-type grain. This may explain why the raised levels of minerals transported to the developing grain accumulate within the crease region of the transgenic grain....

A Neisseria meningitidis fbpABC mutant is incapable of using nonheme iron for growth.

Science.gov (United States)

Khun, H H; Kirby, S D; Lee, B C

1998-05-01

The neisserial fbpABC locus has been proposed to act as an iron-specific ABC transporter system. To confirm this assigned function, we constructed an fbpABC mutant in Neisseria meningitidis by insertional inactivation of fbpABC with a selectable antibiotic marker. The mutant was unable to use iron supplied from human transferrin, human lactoferrin, or iron chelates. However, the use of iron from heme and human hemoglobin was unimpaired. These results support the obligatory participation of fbpABC in neisserial periplasmic iron transport and do not indicate a role for this genetic locus in the heme iron pathway.

KBS-3H. Reactive transport modelling of iron-bentonite interactions, an update for the Olkiluoto case

International Nuclear Information System (INIS)

Birgersson, M.; Wersin, P.

2014-03-01

According to the KBS-3H concept, each copper canister containing spent nuclear fuel will be surrounded by a bentonite buffer and a perforated cylinder. The originally planned material for the perforated steel cylinder shell has been carbon steel. After emplacement, the steel material will corrode anaerobically in contact with water and generate hydrogen, iron species and hydroxyl ions. Iron corrosion products will be formed at the steel surface, but in addition, the released species may interact with the clay and lead to undesirable effects, such as montmorillonite transformation and cementation. The impact of corrosion and iron-bentonite interactions has been assessed for Olkiluoto-specific conditions by reactive transport modelling using the CrunchFlow code. The main focus of this modelling exercise was to update the previous modelling study of Wersin et al. (2007). by accounting for new thermodynamic data on clays and uncertainties in precipitation rates of iron reaction products. The modelling strategy was first to select appropriate thermodynamic and kinetic mineral by review of current data, in particular of the THERMODDEM database, and by chemical equilibrium modelling. Second, a 1D reactive transport model which includes a corroding iron source from which solutes can diffuse into the buffer and interact with the clay and accessory minerals was set up in a similar way as that applied in Wersin et al. (2007). A number of test cases were defined, including a Base Case and various less likely as well as bounding cases. The modelling results largely confirmed previous findings in that the zone of alteration was predicted to remain spatially limited for very long times. However, they highlighted that under unfavourable conditions during the initial corrosion phase (before complete corrosion of the shell), pronounced increase in pH might occur, which would lead to enhanced dissolution of the montmorillonite clay. Factors favouring pH increase were found to be slow

KBS-3H. Reactive transport modelling of iron-bentonite interactions, an update for the Olkiluoto case

Energy Technology Data Exchange (ETDEWEB)

Birgersson, M. [Clay Technology AB, Lund (Sweden); Wersin, P. [Bern Univ. (Switzerland)

2014-03-15

According to the KBS-3H concept, each copper canister containing spent nuclear fuel will be surrounded by a bentonite buffer and a perforated cylinder. The originally planned material for the perforated steel cylinder shell has been carbon steel. After emplacement, the steel material will corrode anaerobically in contact with water and generate hydrogen, iron species and hydroxyl ions. Iron corrosion products will be formed at the steel surface, but in addition, the released species may interact with the clay and lead to undesirable effects, such as montmorillonite transformation and cementation. The impact of corrosion and iron-bentonite interactions has been assessed for Olkiluoto-specific conditions by reactive transport modelling using the CrunchFlow code. The main focus of this modelling exercise was to update the previous modelling study of Wersin et al. (2007). by accounting for new thermodynamic data on clays and uncertainties in precipitation rates of iron reaction products. The modelling strategy was first to select appropriate thermodynamic and kinetic mineral by review of current data, in particular of the THERMODDEM database, and by chemical equilibrium modelling. Second, a 1D reactive transport model which includes a corroding iron source from which solutes can diffuse into the buffer and interact with the clay and accessory minerals was set up in a similar way as that applied in Wersin et al. (2007). A number of test cases were defined, including a Base Case and various less likely as well as bounding cases. The modelling results largely confirmed previous findings in that the zone of alteration was predicted to remain spatially limited for very long times. However, they highlighted that under unfavourable conditions during the initial corrosion phase (before complete corrosion of the shell), pronounced increase in pH might occur, which would lead to enhanced dissolution of the montmorillonite clay. Factors favouring pH increase were found to be slow

Influence of Atmospheric Processes on the Solubility and Composition of Iron in Saharan Dust.

Science.gov (United States)

Longo, Amelia F; Feng, Yan; Lai, Barry; Landing, William M; Shelley, Rachel U; Nenes, Athanasios; Mihalopoulos, Nikolaos; Violaki, Kalliopi; Ingall, Ellery D

2016-07-05

Aerosol iron was examined in Saharan dust plumes using a combination of iron near-edge X-ray absorption spectroscopy and wet-chemical techniques. Aerosol samples were collected at three sites located in the Mediterranean, the Atlantic, and Bermuda to characterize iron at different atmospheric transport lengths and time scales. Iron(III) oxides were a component of aerosols at all sampling sites and dominated the aerosol iron in Mediterranean samples. In Atlantic samples, iron(II and III) sulfate, iron(III) phosphate, and iron(II) silicates were also contributors to aerosol composition. With increased atmospheric transport time, iron(II) sulfates are found to become more abundant, aerosol iron oxidation state became more reduced, and aerosol acidity increased. Atmospheric processing including acidic reactions and photoreduction likely influence the form of iron minerals and oxidation state in Saharan dust aerosols and contribute to increases in aerosol-iron solubility.

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.

Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.

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Jonghan Kim

Full Text Available Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI. Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT and dopamine receptor D(1 (D1R levels were reduced and dopamine receptor D(2 (D2R levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.

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

Science.gov (United States)

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.

[Iron and invasive fungal infection].

Science.gov (United States)

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.

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 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.

Mechanical properties of ductile cast iron and cast steel for intermediate level waste transport containers

International Nuclear Information System (INIS)

Gray, I.L.S.; Sievwright, R.W.T.; Egid, B.; Ajayi, F.; Donelan, P.

1994-01-01

UK Nirex Ltd is developing Type B re-usable shielded transport containers (RSTCs) in a range of shielding thicknesses to transport intermediate level radioactive waste (ILW) to a deep repository. The designs are of an essentially monolithic construction and rely principally on the plastic flow of their material to absorb the energies involved in impact events. Nirex has investigated the feasibility of manufacturing the RSTCs from ductile cast iron (DCI) or cast steel instead of from forgings, since this would bring advantages of reduced manufacturing time and costs. However, cast materials are perceived to lack toughness and ductility and it is necessary to show that sufficient fracture toughness can be obtained to preclude brittle failure modes, particularly at low temperatures. The mechanical testing carried out as part of that programme is described. It shows how the measured properties have been used to demonstrate avoidance of brittle fracture and provide input to computer modelling of the drop tests. (author)

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.

Prion protein modulates glucose homeostasis by altering intracellular iron.

Science.gov (United States)

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.

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

Arsenic enrichment in estuarine sediments-impact of iron and manganese mining

Digital Repository Service at National Institute of Oceanography (India)

Nair, M.; Joseph, T.; Balachandran, K.K.; Nair, K.K.C.; Paimpillii, J.S.

River Mandovi and Zuari, Goa (west coast of India) are flowing through iron and manganese mining areas and are heavily used for iron and manganese ore transport. This region generates 25-30 million tons of mining rejects per year. The iron ore...

Nonlocal magnon spin transport in yttrium iron garnet with tantalum and platinum spin injection/detection electrodes

Science.gov (United States)

Liu, J.; Cornelissen, L. J.; Shan, J.; van Wees, B. J.; Kuschel, T.

2018-06-01

We study the magnon spin transport in the magnetic insulator yttrium iron garnet (YIG) in a nonlocal experiment and compare the magnon spin excitation and detection for the heavy metal paramagnetic electrodes platinum (Pt|YIG|Pt) and tantalum (Ta|YIG|Ta). The electrical injection and detection processes rely on the (inverse) spin Hall effect in the heavy metals and the conversion between the electron spin and magnon spin at the heavy metal|YIG interface. Pt and Ta possess opposite signs of the spin Hall angle. Furthermore, their heterostructures with YIG have different interface properties, i.e. spin mixing conductances. By varying the distance between injector and detector, the magnon spin transport is studied. Using a circuit model based on the diffusion-relaxation transport theory, a similar magnon relaxation length of  ∼10 μm was extracted from both Pt and Ta devices. By changing the injector and detector material from Pt to Ta, the influence of interface properties on the magnon spin transport has been observed. For Ta devices on YIG the spin mixing conductance is reduced compared with Pt devices, which is quantitatively consistent when comparing the dependence of the nonlocal signal on the injector-detector distance with the prediction from the circuit model.

Protein Hydrolysates as Promoters of Non-Haem Iron Absorption

Science.gov (United States)

Li, Yanan; Jiang, Han; Huang, Guangrong

2017-01-01

Iron (Fe) is an essential micronutrient for human growth and health. Organic iron is an excellent iron supplement due to its bioavailability. Both amino acids and peptides improve iron bioavailability and absorption and are therefore valuable components of iron supplements. This review focuses on protein hydrolysates as potential promoters of iron absorption. The ability of protein hydrolysates to chelate iron is thought to be a key attribute for the promotion of iron absorption. Iron-chelatable protein hydrolysates are categorized by their absorption forms: amino acids, di- and tri-peptides and polypeptides. Their structural characteristics, including their size and amino acid sequence, as well as the presence of special amino acids, influence their iron chelation abilities and bioavailabilities. Protein hydrolysates promote iron absorption by keeping iron soluble, reducing ferric iron to ferrous iron, and promoting transport across cell membranes into the gut. We also discuss the use and relative merits of protein hydrolysates as iron supplements. PMID:28617327

Protein Hydrolysates as Promoters of Non-Haem Iron Absorption

Directory of Open Access Journals (Sweden)

Yanan Li

2017-06-01

Full Text Available Iron (Fe is an essential micronutrient for human growth and health. Organic iron is an excellent iron supplement due to its bioavailability. Both amino acids and peptides improve iron bioavailability and absorption and are therefore valuable components of iron supplements. This review focuses on protein hydrolysates as potential promoters of iron absorption. The ability of protein hydrolysates to chelate iron is thought to be a key attribute for the promotion of iron absorption. Iron-chelatable protein hydrolysates are categorized by their absorption forms: amino acids, di- and tri-peptides and polypeptides. Their structural characteristics, including their size and amino acid sequence, as well as the presence of special amino acids, influence their iron chelation abilities and bioavailabilities. Protein hydrolysates promote iron absorption by keeping iron soluble, reducing ferric iron to ferrous iron, and promoting transport across cell membranes into the gut. We also discuss the use and relative merits of protein hydrolysates as iron supplements.

Diffusion of iron in β-iron telluride (Fe1.12Te) by Moessbauer spectroscopy and tracer method

International Nuclear Information System (INIS)

Magara, Masaaki; Tsuji, Toshihide; Naito, Keiji

1993-01-01

The diffusion coefficient of iron in a β-iron telluride (Fe 1.12 Te) polycrystalline sample was measured by Moessbauer diffusional line broadening method which relates to the collapse of coherence in gamma-ray photon by the atomic jump at local sites. The diffusion coefficient of iron along the c-axis in nearly single crystal of β-iron telluride was also measured by tracer technique which shows the results of an atom transport in long distance. The activation energies for the diffusion of iron in Fe 1.12 Te obtained by the Moessbauer spectroscopy and the tracer method were 91.5±5.4 and 106±23 kJ/mol, respectively. The diffusion coefficients of iron in β-iron telluride obtained by Moessbauer line broadening are in fair agreement with the values averaged from that along c-axis obtained by tracer method and that along a- and b-axes obtained from reaction rate constant between iron and tellurium by the previous study of the present authors. (orig.)

The prion-ZIP connection: From cousins to partners in iron uptake

Science.gov (United States)

Singh, Neena; Asthana, Abhishek; Baksi, Shounak; Desai, Vilok; Haldar, Swati; Hari, Sahi; Tripathi, Ajai K

2015-01-01

ABSTRACT Converging observations from disparate lines of inquiry are beginning to clarify the cause of brain iron dyshomeostasis in sporadic Creutzfeldt-Jakob disease (sCJD), a neurodegenerative condition associated with the conversion of prion protein (PrPC), a plasma membrane glycoprotein, from α-helical to a β-sheet rich PrP-scrapie (PrPSc) isoform. Biochemical evidence indicates that PrPC facilitates cellular iron uptake by functioning as a membrane-bound ferrireductase (FR), an activity necessary for the transport of iron across biological membranes through metal transporters. An entirely different experimental approach reveals an evolutionary link between PrPC and the Zrt, Irt-like protein (ZIP) family, a group of proteins involved in the transport of zinc, iron, and manganese across the plasma membrane. Close physical proximity of PrPC with certain members of the ZIP family on the plasma membrane and increased uptake of extracellular iron by cells that co-express PrPC and ZIP14 suggest that PrPC functions as a FR partner for certain members of this family. The connection between PrPC and ZIP proteins therefore extends beyond common ancestry to that of functional cooperation. Here, we summarize evidence supporting the facilitative role of PrPC in cellular iron uptake, and implications of this activity on iron metabolism in sCJD brains. PMID:26689487

Photoreduction of Terrigenous Fe-Humic Substances Leads to Bioavailable Iron in Oceans.

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Blazevic, Amir; Orlowska, Ewelina; Kandioller, Wolfgang; Jirsa, Franz; Keppler, Bernhard K; Tafili-Kryeziu, Myrvete; Linert, Wolfgang; Krachler, Rudolf F; Krachler, Regina; Rompel, Annette

2016-05-23

Humic substances (HS) are important iron chelators responsible for the transport of iron from freshwater systems to the open sea, where iron is essential for marine organisms. Evidence suggests that iron complexed to HS comprises the bulk of the iron ligand pool in near-coastal waters and shelf seas. River-derived HS have been investigated to study their transport to, and dwell in oceanic waters. A library of iron model compounds and river-derived Fe-HS samples were probed in a combined X-ray absorption spectroscopy (XAS) and valence-to-core X-ray emission spectroscopy (VtC-XES) study at the Fe K-edge. The analyses performed revealed that iron complexation in HS samples is only dependent on oxygen-containing HS functional groups, such as carboxyl and phenol. The photoreduction mechanism of Fe III -HS in oceanic conditions into bioavailable aquatic Fe II forms, highlights the importance of river-derived HS as an iron source for marine organisms. Consequently, such mechanisms are a vital component of the upper-ocean iron biogeochemistry cycle.

Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages.

Science.gov (United States)

Cutone, Antimo; Rosa, Luigi; Lepanto, Maria Stefania; Scotti, Mellani Jinnett; Berlutti, Francesca; Bonaccorsi di Patti, Maria Carmela; Musci, Giovanni; Valenti, Piera

2017-01-01

Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in "pure" M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp, cytosolic Ftn, and

Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages

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Antimo Cutone

2017-06-01

Full Text Available Human lactoferrin (hLf, an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf, which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in “pure” M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml, the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn, membrane-bound ceruloplasmin (Cp, cytosolic ferritin (Ftn, transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp

Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

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Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

2017-01-01

Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2). The BPAN patients showed a concomitant increase of intracellular ferrous iron after starvation. An altered pattern of iron transporters with iron overload is highlighted in BPAN human fibroblasts, supporting for a role of DMT1 in NBIA. We here present a novel element, about iron accumulation, to the existing knowledge in field of NBIA. Attention is focused to a starvation-dependent iron overload, possibly accounting for iron accumulation in the basal ganglia. Further investigation could clarify iron regulation in BPAN.

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.

Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis

DEFF Research Database (Denmark)

Srinivasan, Gayathri; Aitken, Jesse D; Zhang, Benyue

2012-01-01

Various states of inflammation, including sepsis, are associated with hypoferremia, which limits iron availability to pathogens and reduces iron-mediated oxidative stress. Lipocalin 2 (Lcn2; siderocalin, 24p3) plays a central role in iron transport. Accordingly, Lcn2-deficient (Lcn2KO) mice exhib...

Transport proteins promoting Escherichia coli pathogenesis

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Tang, Fengyi; Saier, Milton H.

2014-01-01

Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. PMID:24747185

Transport proteins promoting Escherichia coli pathogenesis.

Science.gov (United States)

Tang, Fengyi; Saier, Milton H

2014-01-01

Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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

78 FR 34160 - Union Pacific Railroad Company-Abandonment Exemption-In Iron County, Utah

Science.gov (United States)

2013-06-06

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. AB 33 (Sub-No. 283X)] Union Pacific Railroad Company--Abandonment Exemption--In Iron County, Utah Union Pacific Railroad Company (UP... Cedar City, a total distance of 1.03 miles in Iron County, Utah (the Line). The Line traverses United...

Studying disorders of vertebrate iron and heme metabolism using zebrafish.

Science.gov (United States)

van der Vorm, Lisa N; Paw, Barry H

2017-01-01

Iron is a crucial component of heme- and iron-sulfur clusters, involved in vital cellular functions such as oxygen transport, DNA synthesis, and respiration. Both excess and insufficient levels of iron and heme-precursors cause human disease, such as iron-deficiency anemia, hemochromatosis, and porphyrias. Hence, their levels must be tightly regulated, requiring a complex network of transporters and feedback mechanisms. The use of zebrafish to study these pathways and the underlying genetics offers many advantages, among others their optical transparency, ex-vivo development and high genetic and physiological conservations. This chapter first reviews well-established methods, such as large-scale mutagenesis screens that have led to the initial identification of a series of iron and heme transporters and the generation of a variety of mutant lines. Other widely used techniques are based on injection of RNA, including complementary morpholino knockdown and gene overexpression. In addition, we highlight several recently developed approaches, most notably endonuclease-based gene knockouts such as TALENs or the CRISPR/Cas9 system that have been used to study how loss of function can induce human disease phenocopies in zebrafish. Rescue by chemical complementation with iron-based compounds or small molecules can subsequently be used to confirm causality of the genetic defect for the observed phenotype. All together, zebrafish have proven to be - and will continue to serve as an ideal model to advance our understanding of the pathogenesis of human iron and heme-related diseases and to develop novel therapies to treat these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

Natural resources sustainability: iron ore mining

International Nuclear Information System (INIS)

De La Torre de Palacios, Luis

2011-01-01

In the present article, a new tool to determine environmental sustainability, the energy impact index (EII) was developed to classify different iron mine projects according to two main parameters including energy consumption and CO 2 emissions. The EII considers the characteristics of the mineral (such as the quality, size, hardness, iron ore grade, reducibility, mineral/waste rate, and type of deposit), mining processes (type of exploitation, ore processing, available technology), and transportation (distance to cover).

Cast iron transport, storage and disposal containers for use in UK nuclear licensed sites - 59412

International Nuclear Information System (INIS)

Viermann, Joerg; Messer, Matthias P.

2012-01-01

Document available in abstract form only. Full text of publication follows: Ductile Cast Iron Containers of the types GCVI (UK trademark -GNS YELLOW BOX R ) and MOSAIK R have been in use in Germany for transport, storage and disposal of intermediate level radioactive waste (ILW) for more than two decades. In 2009 a number of containers of these types were delivered to various Magnox sites as so called pathfinders to test their suitability for Magnox waste streams. The results were encouraging. Therefore the Letter of Compliance (LoC) procedure was started to prove the suitability of packages using these types of containers for the future UK Geological Disposal Facility (GDF) and a conceptual Letter of Compliance (cLoC) was obtained from RWMD in 2010. Waste stream specific applications for Interim Stage Letters of Compliance (ILoC) for a number of waste streams from different Magnox sites and from the UK's only pressurised water reactor, Sizewell B are currently being prepared and discussed with RWMD. In order to achieve a package suitable for interim storage and disposal the contents of a Ductile Cast Iron Container only has to be dried. Mobile drying facilities are readily available. Containers and drying facilities form a concerted system

Immunity to plant pathogens and iron homeostasis.

Science.gov (United States)

Aznar, Aude; Chen, Nicolas W G; Thomine, Sebastien; Dellagi, Alia

2015-11-01

Iron is essential for metabolic processes in most living organisms. Pathogens and their hosts often compete for the acquisition of this nutrient. However, iron can catalyze the formation of deleterious reactive oxygen species. Hosts may use iron to increase local oxidative stress in defense responses against pathogens. Due to this duality, iron plays a complex role in plant-pathogen interactions. Plant defenses against pathogens and plant response to iron deficiency share several features, such as secretion of phenolic compounds, and use common hormone signaling pathways. Moreover, fine tuning of iron localization during infection involves genes coding iron transport and iron storage proteins, which have been shown to contribute to immunity. The influence of the plant iron status on the outcome of a given pathogen attack is strongly dependent on the nature of the pathogen infection strategy and on the host species. Microbial siderophores emerged as important factors as they have the ability to trigger plant defense responses. Depending on the plant species, siderophore perception can be mediated by their strong iron scavenging capacity or possibly via specific recognition as pathogen associated molecular patterns. This review highlights that iron has a key role in several plant-pathogen interactions by modulating immunity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Aquifer Thermal Energy Storage as an ecosystem service for Brussels, Belgium: investigating iron (hydr)oxide precipitation with reactive transport modeling

Science.gov (United States)

Anibas, Christian; Possemiers, Mathias; Huysmans, Marijke

2016-04-01

In an evolving energy system it is important that urbanized areas contribute to their own energy demands. To reduce greenhouse gas emissions sustainable energy systems with a high efficiency are required, e.g. using urban aquifers as an ecosystem service. Here the potential of seasonal aquifer thermal energy storage and recovery (ATES) for the Brussels-Capital Region, Belgium is investigated. An important shallow geologic formation in the Brussels Capital Region is the Brussels Sand formation, a 20-60 m thick phreatic aquifer. The Brussels Sand Formation is known for its potential for ATES systems, but also for its varying redox and hydraulic conditions. Important limiting factors for ATES systems in the Brussels Sand Formation therefore are the hydraulic conductivity and the geochemical composition of the groundwater. Near the redox boundary iron hydroxide precipitation can negatively influence ATES well performance due to clogging. The interactions between physical processes (e.g. particle transport and clogging in the wider proximity of the ATES well) and chemical processes (e.g. influence of the operation temperatures on precipitation processes) during ATES operation are complex but not well understood. Therefore we constructed numerical groundwater flow models in MODFLOW to estimate maximum pumping and injection rates of different hydraulic conditions and competing water uses in the Brussels Sand Formation. In further steps the thermal potential for ATES was quantified using MT3DMS and the reactive transport model PHT3D was applied to assess the effects of operating ATES systems near the redox boundary. Results show that initial mixing plays an important role in the development of iron(hydr)oxide precipitation around the ATES wells, with the highest concentrations around the cold wells. This behavior is enhanced by the temperature effect; temperature differences of ΔT≈10°C already influence the iron (hydr)oxide concentration. The initial injection into the

Structure of Stenotrophomonas maltophilia FeoA complexed with zinc: a unique prokaryotic SH3-domain protein that possibly acts as a bacterial ferrous iron-transport activating factor

International Nuclear Information System (INIS)

Su, Yi-Che; Chin, Ko-Hsin; Hung, Hui-Chih; Shen, Gwan-Han; Wang, Andrew H.-J.; Chou, Shan-Ho

2010-01-01

The crystal structure of FeoA from Stenotrophomonas maltophilia has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach and revealed a unique dimer cross-linked by two zinc ions and six chloride ions. Iron is vital to the majority of prokaryotes, with ferrous iron believed to be the preferred form for iron uptake owing to its much better solubility. The major route for bacterial ferrous iron uptake is found to be via an Feo (ferrous iron-transport) system comprising the three proteins FeoA, FeoB and FeoC. Although the structure and function of FeoB have received much attention recently, the roles played by FeoA and FeoC have been little investigated to date. Here, the tertiary structure of FeoA from Stenotrophomonas maltophilia (Sm), a vital opportunistic pathogen in immunodepressed hosts, is reported. The crystal structure of SmFeoA has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach. Although SmFeoA bears low sequence identity to eukaryotic proteins, its structure is found to adopt a eukaryotic SH3-domain-like fold. It also bears weak similarity to the C-terminal SH3 domain of bacterial DtxR (diphtheria toxin regulator), with some unique characteristics. Intriguingly, SmFeoA is found to adopt a unique dimer cross-linked by two zinc ions and six anions (chloride ions). Since FeoB has been found to contain a G-protein-like domain with low GTPase activity, FeoA may interact with FeoB through the SH3–G-protein domain interaction to act as a ferrous iron-transport activating factor

Challenges facing the North American iron ore industry

Science.gov (United States)

Jorgenson, J.D.

2005-01-01

During the 20th century, the iron ore mining industries of Canada and the United States passed through several periods of transformation. The beginning of the 21st century has seen yet another period of transformation, with the economic failure of a number of steel companies, the acquisition of their facilities by more viable steelmakers, and the consolidation of control within the North American iron ore industry. Changes in Canadian and United States iron ore production and the market control structure involved are analysed. The consolidation of ownership, formation of foreign joint ventures within Nordi America, planned divestitures of upstream activities by steelmakers, and industry changes made to ensure availability of feedstocks will be reviewed. The ttaditional isolation of the Canadian and United States iron ore operations and their strong linkage to downstream steel production will be discussed in the context of a changing global economy. Management-labour conflicts that have taken place and agreements made during 2000 through 2004 will be discussed in the context of the economic environment leading up to these agreements. Cooperative agreements between competing Canadian and United States companies to resolve client needs in processing and blending will be examined. A joint industry-government project designed to use new technology to produce direct reduced iron nuggets of 96 - 98 per cent iron content using non-coking coals will also be assessed. Changes in iron ore transportation methods, ownership and infrastructure will be reviewed for both rail and inland waterway transport between Canadian and United States companies. A brief analysis of social and environmental issues relating to sustainable development of the Canadian-United States iron ore industry will be included.

Solubility of iron from combustion source particles in acidic media linked to iron speciation.

Science.gov (United States)

Fu, Hongbo; Lin, Jun; Shang, Guangfeng; Dong, Wenbo; Grassian, Vichi H; Carmichael, Gregory R; Li, Yan; Chen, Jianmin

2012-10-16

In this study, iron solubility from six combustion source particles was investigated in acidic media. For comparison, a Chinese loess (CL) dust was also included. The solubility experiments confirmed that iron solubility was highly variable and dependent on particle sources. Under dark and light conditions, the combustion source particles dissolved faster and to a greater extent relative to CL. Oil fly ash (FA) yielded the highest soluble iron as compared to the other samples. Total iron solubility fractions measured in the dark after 12 h ranged between 2.9 and 74.1% of the initial iron content for the combustion-derived particles (Oil FA > biomass burning particles (BP) > coal FA). Ferrous iron represented the dominant soluble form of Fe in the suspensions of straw BP and corn BP, while total dissolved Fe presented mainly as ferric iron in the cases of oil FA, coal FA, and CL. Mössbauer measurements and TEM analysis revealed that Fe in oil FA was commonly presented as nanosized Fe(3)O(4) aggregates and Fe/S-rich particles. Highly labile source of Fe in corn BP could be originated from amorphous Fe form mixed internally with K-rich particles. However, Fe in coal FA was dominated by the more insoluble forms of both Fe-bearing aluminosilicate glass and Fe oxides. The data presented herein showed that iron speciation varies by source and is an important factor controlling iron solubility from these anthropogenic emissions in acidic solutions, suggesting that the variability of iron solubility from combustion-derived particles is related to the inherent character and origin of the aerosols themselves. Such information can be useful in improving our understanding on iron solubility from combustion aerosols when they undergo acidic processing during atmospheric transport.

Fabrication, characterization and applications of iron selenide

Energy Technology Data Exchange (ETDEWEB)

Hussain, Raja Azadar, E-mail: hussainazadar@yahoo.com [Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad (Pakistan); Badshah, Amin [Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad (Pakistan); Lal, Bhajan [Department of Energy Systems Engineering, Sukkur Institute of Business Administration (Pakistan)

2016-11-15

This review article presents fabrication of FeSe by solid state reactions, solution chemistry routes, chemical vapor deposition, spray pyrolysis and chemical vapor transport. Different properties and applications such as crystal structure and phase transition, band structure, spectroscopy, superconductivity, photocatalytic activity, electrochemical sensing, and fuel cell activity of FeSe have been discussed. - Graphical abstract: Iron selenide can be synthesized by solid state reactions, chemical vapor deposition, solution chemistry routes, chemical vapor transport and spray pyrolysis. - Highlights: • Different fabrication methods of iron selenide (FeSe) have been reviewed. • Crystal structure, band structure and spectroscopy of FeSe have been discussed. • Superconducting, catalytic and fuel cell application of FeSe have been presented.

Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

DEFF Research Database (Denmark)

Schonberg, David L; Miller, Tyler E; Wu, Qiulian

2015-01-01

Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue......, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable...

Isolation and characterisation of EfeM, a periplasmic component of the putative EfeUOBM iron transporter of Pseudomonas syringae pv. syringae

Energy Technology Data Exchange (ETDEWEB)

Rajasekaran, Mohan B [School of Biological Sciences Harborne Building, Whiteknights Campus, Reading, RG6 6AS (United Kingdom); Structural Biology Unit at The BioCentre, University of Reading, Harborne Building, Whiteknights Campus, Reading, RG6 6AS (United Kingdom); Mitchell, Sue A; Gibson, Trevor M [Structural Biology Unit at The BioCentre, University of Reading, Harborne Building, Whiteknights Campus, Reading, RG6 6AS (United Kingdom); Hussain, Rohanah; Siligardi, Giuliano [Circular Dichroism Group, Diamond Light Source, Chiltern, Oxfordshire,OX11 0DE (United Kingdom); Andrews, Simon C [School of Biological Sciences Harborne Building, Whiteknights Campus, Reading, RG6 6AS (United Kingdom); Watson, Kimberly A, E-mail: k.a.watson@reading.ac.uk [School of Biological Sciences Harborne Building, Whiteknights Campus, Reading, RG6 6AS (United Kingdom); Structural Biology Unit at The BioCentre, University of Reading, Harborne Building, Whiteknights Campus, Reading, RG6 6AS (United Kingdom)

2010-07-30

Research highlights: {yields} Bioinformatic analysis reveals EfeM is a metallopeptidase with conserved HXXE motif. {yields} Mass spectrometry confirms EfeM consists of 251 residues, molecular weight 27,772Da. {yields} SRCD spectroscopy shows an {alpha}-helical secondary structure. {yields} Single crystals of EfeM are orthorhombic and diffract to 1.6A resolution. {yields} Space group is P22{sub 1}2{sub 1} with cell dimensions a = 46.74, b = 95.17 and c = 152.61 A. -- Abstract: The EfeM protein is a component of the putative EfeUOBM iron-transporter of Pseudomonas syringae pathovar syringae and is thought to act as a periplasmic, ferrous-iron binding protein. It contains a signal peptide of 34 amino acid residues and a C-terminal 'Peptidase{sub M}75' domain of 251 residues. The C-terminal domain contains a highly conserved 'HXXE' motif thought to act as part of a divalent cation-binding site. In this work, the gene (efeM or 'Psyr{sub 3}370') encoding EfeM was cloned and over-expressed in Escherichia coli, and the mature protein was purified from the periplasm. Mass spectrometry confirmed the identity of the protein (M{sub W} 27,772 Da). Circular dichroism spectroscopy of EfeM indicated a mainly {alpha}-helical structure, consistent with bioinformatic predictions. Purified EfeM was crystallised by hanging-drop vapor diffusion to give needle-shaped crystals that diffracted to a resolution of 1.6 A. This is the first molecular study of a peptidase M75 domain with a presumed iron transport role.

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

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Yu. P. Orlov

2006-01-01

Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

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.

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.

Iron transport across the skin and gut epithelia of Pacific hagfish: Kinetic characterisation and effect of hypoxia.

Science.gov (United States)

Glover, Chris N; Niyogi, Som; Blewett, Tamzin A; Wood, Chris M

2016-09-01

In most animals, the acquisition of the essential trace metal iron (Fe) is achieved by the gut, but in hagfishes, the skin is a nutrient absorbing epithelium, and thus may also play a role in Fe uptake. In the current study, the absorption of Fe, as Fe(II), across the intestinal and cutaneous epithelia of Pacific hagfish (Eptatretus cirrhatus) was investigated. Both epithelia absorbed Fe, with saturation at lower tested concentrations, superseded by a diffusive component at higher Fe exposure concentrations. Affinity constants (Km) of 9.4 and 137μM, and maximal Fe transport rates (Jmax) of 0.81 and 0.57nmolcm(-2)h(-1) were determined for the skin and the gut, respectively. This characterises the skin as a relatively high-affinity Fe transport epithelium. The majority of the absorbed Fe in the skin remained in the tissue, whereas in the gut, most absorbed Fe was found in the serosal fluid, suggesting distinct mechanisms of Fe handling between the two epithelia. To determine if reduced dissolved oxygen altered Fe transport, hagfish were subjected to hypoxia for 24h, before Fe transport was again assessed. Hypoxia had no effect on Fe transport across gut or skin, likely owing to the relative lack of change in haematological variables, and thus an unaltered Fe demand under such conditions. These data are the first to kinetically characterise the absorption of a nutritive trace metal across the epithelia of hagfish and add to the growing understanding of the role of the skin in nutritive transport in this group. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficiency increase of complex production and transport systems management

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Kornilov S.

2017-01-01

Full Text Available This article deals with the problem of the reduced efficiency of management in complex production - transport systems due to the lack of co-ordination in the operation of industrial enterprises and transport carrying out their maintenance. The existing transport service schedules for auxiliary departments do not take into account possible changes in operating conditions, the probability of malfunctions and the amount of reserves, which leads to an increase in general production costs. To solve this problem, we propose to use the interval regulation of production and transport processes in all departments of the complex production and transport systems. Also, such regulation involves the determination of traffic service priority. This will allow passing on from the regulated control of production and transport processes to the situational one, adapted to specific conditions, and reducing losses from untimely transport servicing, which will lead to a stores reduction and efficiency increase of the enterprise circulating facilities use. Testing the effectiveness of interval regulation was performed on the system and dynamics simulation model of liquid iron transportation in the oxygen converter shop of the metallurgical enterprise. It was established that the use of interval regulation processes in iron production and its transportation will allow decreasing non-productive downtime by 21% and the amount of the liquid iron in anticipation of recasting in the oxygen converter shop – by 33%. Economical effect of reducing the liquid iron downtime during transportation to the oxygen converter shop will be about 30 million rubles per year.

Identification of iron-regulated genes of Bifidobacterium breve UCC2003 as a basis for controlled gene expression.

NARCIS (Netherlands)

Cronin, M.; Zomer, A.L.; Fitzgerald, G.F.; Sinderen, D. van

2012-01-01

Iron is an essential growth factor for virtually all organisms. However, iron is not readily available in most environments and microorganisms have evolved specialized mechanisms, such as the use of siderophores and high-affinity transport systems, to acquire iron when confronted with iron-limiting

Production, regulation and transportation of bacillibactin in bacillus subtilis

International Nuclear Information System (INIS)

Raza, W.; Hussain, Q.; Shen, Q.

2012-01-01

Bacillus subtilis produces a catecholate type siderophore 'Bacillibactin'. This review focuses on the non-ribosomal synthesis, transport and regulation of bacillibactin. Bacillibactin biosynthetic operon contains five genes (dhbACEBF). The uptake of bacillibactin requires the FeuABC transporter, inner-membrane permease, FepDG and YusV ATPase and an esterase encoding gene, besA and while export required YmfE major facilitator super-family (MFS)-type transporter. Fur is the major iron-controlled transcriptional regulator in B. subtilis, which acts as an iron-dependent repressor of the dhb operon in vivo while an iron-independent repressor in vitro. Knowledge of the Fur regulon will be useful in interpreting other global analysis of transcriptional responses. (author)

Siderophores as iron storage compounds in the yeasts Rhodotorula minuta and Ustilago sphaerogena detected by in vivo Moessbauer spectroscopy

International Nuclear Information System (INIS)

Matzanke, B.F.; Winkelmann, G.; Bill, E.; Trautwein, A.X.

1990-01-01

In the yeasts Rhodotorula minuta and Ustilago sphaerogena siderophores represent the main intracellular iron pool. We suggest a ferritin substituting function of these siderophores in addition to their role as iron transport agents. In Rhodotorula transport and storage siderophore is the same compound whereas in Ustilago the iron-storage siderophore is ferrichrome. Besides siderophores, merely two iron metabolites can be observed. Other iron-requiring compounds are at least one order of magnitude less abundant in these yeasts. The ferrous metabolite has been detected in many other microbial systems and seems to be of general occurence and importance. (orig.)

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.

Iron and genome stability: An update

International Nuclear Information System (INIS)

Prá, Daniel; Franke, Silvia Isabel Rech; Henriques, João Antonio Pêgas; Fenech, Michael

2012-01-01

Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40–45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

Iron and genome stability: An update

Energy Technology Data Exchange (ETDEWEB)

Pra, Daniel, E-mail: daniel_pra@yahoo.com [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); PPG em Saude e Comportamento, Universidade Catolica de Pelotas, Pelotas, RS (Brazil); Franke, Silvia Isabel Rech [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); Henriques, Joao Antonio Pegas [Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS (Brazil); Fenech, Michael [CSIRO Food and Nutritional Sciences, Adelaide, SA (Australia)

2012-05-01

Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40-45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

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...

Soluble iron nutrients in Saharan dust over the central Amazon rainforest

Science.gov (United States)

Rizzolo, Joana A.; Barbosa, Cybelli G. G.; Borillo, Guilherme C.; Godoi, Ana F. L.; Souza, Rodrigo A. F.; Andreoli, Rita V.; Manzi, Antônio O.; Sá, Marta O.; Alves, Eliane G.; Pöhlker, Christopher; Angelis, Isabella H.; Ditas, Florian; Saturno, Jorge; Moran-Zuloaga, Daniel; Rizzo, Luciana V.; Rosário, Nilton E.; Pauliquevis, Theotonio; Santos, Rosa M. N.; Yamamoto, Carlos I.; Andreae, Meinrat O.; Artaxo, Paulo; Taylor, Philip E.; Godoi, Ricardo H. M.

2017-02-01

The intercontinental transport of aerosols from the Sahara desert plays a significant role in nutrient cycles in the Amazon rainforest, since it carries many types of minerals to these otherwise low-fertility lands. Iron is one of the micronutrients essential for plant growth, and its long-range transport might be an important source for the iron-limited Amazon rainforest. This study assesses the bioavailability of iron Fe(II) and Fe(III) in the particulate matter over the Amazon forest, which was transported from the Sahara desert (for the sake of our discussion, this term also includes the Sahel region). The sampling campaign was carried out above and below the forest canopy at the ATTO site (Amazon Tall Tower Observatory), a near-pristine area in the central Amazon Basin, from March to April 2015. Measurements reached peak concentrations for soluble Fe(III) (48 ng m-3), Fe(II) (16 ng m-3), Na (470 ng m-3), Ca (194 ng m-3), K (65 ng m-3), and Mg (89 ng m-3) during a time period of dust transport from the Sahara, as confirmed by ground-based and satellite remote sensing data and air mass backward trajectories. Dust sampled above the Amazon canopy included primary biological aerosols and other coarse particles up to 12 µm in diameter. Atmospheric transport of weathered Saharan dust, followed by surface deposition, resulted in substantial iron bioavailability across the rainforest canopy. The seasonal deposition of dust, rich in soluble iron, and other minerals is likely to assist both bacteria and fungi within the topsoil and on canopy surfaces, and especially benefit highly bioabsorbent species. In this scenario, Saharan dust can provide essential macronutrients and micronutrients to plant roots, and also directly to plant leaves. The influence of this input on the ecology of the forest canopy and topsoil is discussed, and we argue that this influence would likely be different from that of nutrients from the weathered Amazon bedrock, which otherwise provides the

Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

Science.gov (United States)

Taveggia, Carla

2014-01-01

Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

Basin-scale transport of hydrothermal dissolved metals across the South Pacific Ocean.

Science.gov (United States)

Resing, Joseph A; Sedwick, Peter N; German, Christopher R; Jenkins, William J; Moffett, James W; Sohst, Bettina M; Tagliabue, Alessandro

2015-07-09

Hydrothermal venting along mid-ocean ridges exerts an important control on the chemical composition of sea water by serving as a major source or sink for a number of trace elements in the ocean. Of these, iron has received considerable attention because of its role as an essential and often limiting nutrient for primary production in regions of the ocean that are of critical importance for the global carbon cycle. It has been thought that most of the dissolved iron discharged by hydrothermal vents is lost from solution close to ridge-axis sources and is thus of limited importance for ocean biogeochemistry. This long-standing view is challenged by recent studies which suggest that stabilization of hydrothermal dissolved iron may facilitate its long-range oceanic transport. Such transport has been subsequently inferred from spatially limited oceanographic observations. Here we report data from the US GEOTRACES Eastern Pacific Zonal Transect (EPZT) that demonstrate lateral transport of hydrothermal dissolved iron, manganese, and aluminium from the southern East Pacific Rise (SEPR) several thousand kilometres westward across the South Pacific Ocean. Dissolved iron exhibits nearly conservative (that is, no loss from solution during transport and mixing) behaviour in this hydrothermal plume, implying a greater longevity in the deep ocean than previously assumed. Based on our observations, we estimate a global hydrothermal dissolved iron input of three to four gigamoles per year to the ocean interior, which is more than fourfold higher than previous estimates. Complementary simulations with a global-scale ocean biogeochemical model suggest that the observed transport of hydrothermal dissolved iron requires some means of physicochemical stabilization and indicate that hydrothermally derived iron sustains a large fraction of Southern Ocean export production.

New perspectives on the regulation of iron absorption via cellular zinc concentrations in humans.

Science.gov (United States)

Knez, Marija; Graham, Robin D; Welch, Ross M; Stangoulis, James C R

2017-07-03

Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.

Moessbauer study of iron uptake in cucumber root

Energy Technology Data Exchange (ETDEWEB)

Kovacs, K.; Kuzmann, E., E-mail: kuzmann@para.chem.elte.hu [Eoetvoes Lorand University, Research Group for Nuclear Methods in Structural Chemistry, Hungarian Academy of Sciences, Department of Nuclear Chemistry (Hungary); Fodor, F. [Eoetvoes Lorand University, Department of Plant Physiology and Molecular Plant Biology (Hungary); Vertes, A. [Eoetvoes Lorand University, Research Group for Nuclear Methods in Structural Chemistry, Hungarian Academy of Sciences, Department of Nuclear Chemistry (Hungary); Kamnev, A. A. [Russian Academy of Sciences, Institute of Biochemistry and Physiology of Plants and Microorganisms (Russian Federation)

2005-09-15

{sup 57}Fe Moessbauer spectroscopy was used to study the uptake and distribution of iron in the root of cucumber plants grown in iron-deficient modified Hoagland nutrient solution and put into iron-containing solution with 10 {mu}M Fe citrate enriched with {sup 57}Fe (90%) only before harvesting. The Moessbauer spectra of the frozen roots exhibited two Fe{sup 3+} components with typical average Moessbauer parameters of {delta} = 0.5 mm s{sup -1}, {Delta} = 0.46 mm s{sup -1} and {delta} = 0.5 mm s{sup -1}, {Delta} = 1.2 mm s{sup -1} at 78 K and the presence of an Fe{sup 2+} doublet, assigned to the ferrous hexaaqua complex. This finding gives a direct evidence for the existence of Fe{sup 2+} ions produced via root-associated reduction according to the mechanism proposed for iron uptake for dicotyledonous plants. Monotonous changes in the relative content of the components were found with the time period of iron supply. The Moessbauer results are interpreted in terms of iron uptake and transport through the cell wall and membranes.

Siderophores as iron storage compounds in the yeasts Rhodotorula minuta and Ustilago sphaerogena detected by in vivo Mössbauer spectroscopy

Science.gov (United States)

Matzanke, B. F.; Bill, E.; Trautwein, A. X.; Winkelmann, G.

1990-07-01

In the yeasts Rhodotorula minuta and Ustilago sphaerogena siderophores represent the main intracellular iron pool. We suggest a ferritin substituting function of these siderophores in addition to their role as iron transport agents. In Rhodotorula transport and storage siderophore is the same compound whereas in Ustilago the iron-storage siderophore is ferrichrome. Besides siderophores, merely two iron metabolites can be observed. Other iron-requiring compounds are at least one order of magnitude less abundant in these yeasts. The ferrous metabolite has been detected in many other microbial systems and seems to be of general occurence and importance.

Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

Science.gov (United States)

Hudson, Benjamin H.; Hale, Andrew T.; Irving, Ryan P.; Li, Shenglan; York, John D.

2018-01-01

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis. PMID:29507250

Benchmark analysis of MCNP trademark ENDF/B-VI iron

International Nuclear Information System (INIS)

Court, J.D.; Hendricks, J.S.

1994-12-01

The MCNP ENDF/B-VI iron cross-section data was subjected to four benchmark studies as part of the Hiroshima/Nagasaki dose re-evaluation for the National Academy of Science and the Defense Nuclear Agency. The four benchmark studies were: (1) the iron sphere benchmarks from the Lawrence Livermore Pulsed Spheres; (2) the Oak Ridge National Laboratory Fusion Reactor Shielding Benchmark; (3) a 76-cm diameter iron sphere benchmark done at the University of Illinois; (4) the Oak Ridge National Laboratory Benchmark for Neutron Transport through Iron. MCNP4A was used to model each benchmark and computational results from the ENDF/B-VI iron evaluations were compared to ENDF/B-IV, ENDF/B-V, the MCNP Recommended Data Set (which includes Los Alamos National Laboratory Group T-2 evaluations), and experimental data. The results show that the ENDF/B-VI iron evaluations are as good as, or better than, previous data sets

Iron overload impact on P-ATPases.

Science.gov (United States)

Sousa, Leilismara; Pessoa, Marco Tulio C; Costa, Tamara G F; Cortes, Vanessa F; Santos, Herica L; Barbosa, Leandro Augusto

2018-03-01

Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na + ,K + -ATPase and the Ca 2+ -ATPase. On the Fe 2+ -ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe 2+ and playing a protection role for the cell. On the Ca 2+ -ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca 2+ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca 2+ concentrations, which could promote an enzyme oxidation, nitration, and fragmentation. However, the iron overload effect on the Na + ,K + -ATPase may change according to the tissue expressions. On the renal cells, as well as on the brain and the heart, iron promotes an enzyme inactivation, whereas its effect on the erythrocytes seems to be the opposite, directly stimulating the ATPase activity, or stimulating it by signaling pathways involving ROS and PKC. Modulations in the ATPase activity may impair the ionic transportation, which is essential for cell viability maintenance, inducing irreversible damage to the cell homeostasis. Here, we will discuss about the iron overload effect on the P-ATPases, such as the Na + ,K + -ATPase, the Ca 2+ -ATPase, and the Fe 2+ -ATPase.

Quantum oscillations and ferromagnetic hysteresis observed in iron filled multiwall carbon nanotubes.

Science.gov (United States)

Barzola-Quiquia, J; Klingner, N; Krüger, J; Molle, A; Esquinazi, P; Leonhardt, A; Martínez, M T

2012-01-13

We report on the electrical transport properties of single multiwall carbon nanotubes with and without an iron filling as a function of temperature and magnetic field. For the iron filled nanotubes the magnetoresistance shows a magnetic behavior induced by iron, which can be explained by taking into account a contribution of s-d hybridization. In particular, ferromagnetic-like hysteresis loops were observed up to 50 K for the iron filled multiwall carbon nanotubes. The magnetoresistance shows quantum interference phenomena such as universal conductance fluctuations and weak localization effects.

Enhanced Iron Solubility at Low pH in Global Aerosols

Directory of Open Access Journals (Sweden)

Ellery D. Ingall

2018-05-01

Full Text Available The composition and oxidation state of aerosol iron were examined using synchrotron-based iron near-edge X-ray absorption spectroscopy. By combining synchrotron-based techniques with water leachate analysis, impacts of oxidation state and mineralogy on aerosol iron solubility were assessed for samples taken from multiple locations in the Southern and the Atlantic Oceans; and also from Noida (India, Bermuda, and the Eastern Mediterranean (Crete. These sampling locations capture iron-containing aerosols from different source regions with varying marine, mineral dust, and anthropogenic influences. Across all locations, pH had the dominating influence on aerosol iron solubility. When aerosol samples were approximately neutral pH, iron solubility was on average 3.4%; when samples were below pH 4, the iron solubility increased to 35%. This observed aerosol iron solubility profile is consistent with thermodynamic predictions for the solubility of Fe(III oxides, the major iron containing phase in the aerosol samples. Source regions and transport paths were also important factors affecting iron solubility, as samples originating from or passing over populated regions tended to contain more soluble iron. Although the acidity appears to affect aerosol iron solubility globally, a direct relationship for all samples is confounded by factors such as anthropogenic influence, aerosol buffer capacity, mineralogy and physical processes.

Hepcidin: an important iron metabolism regulator in chronic kidney disease.

Science.gov (United States)

Antunes, Sandra Azevedo; Canziani, Maria Eugênia Fernandes

2016-01-01

Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production. The elevation of hepcidin has been associated with infection, inflammation, atherosclerosis, insulin resistance and oxidative stress. Some strategies were tested to reduce the effects of hepcidin in patients with CKD, however more studies are necessary to assess the impact of its modulation in the management of anemia in this population. Resumo Anemia é uma complicação frequente e seu impacto na morbimortalidade é bem conhecido em pacientes com doença renal crônica (DRC). A descoberta da hepcidina e de suas funções contribuíram para melhor compreensão dos distúrbios do metabolismo de ferro na anemia da DRC. Hepcidina é um peptídeo produzido principalmente pelos hepatócitos, e através de sua ligação com a ferroportina, regula a absorção de ferro no duodeno e sua liberação das células de estoque. Altas concentrações de hepcidina descritas em pacientes com DRC, principalmente em estádios mais avançados, são atribuídas à diminuição da excreção renal e ao aumento de sua produção. Elevação de hepcidina tem sido associada à ocorrência de infecção, inflamação, aterosclerose, resistência à insulina e estresse oxidativo. Algumas estratégias foram testadas para diminuir os efeitos da hepcidina em pacientes com DRC, entretanto, serão necessários mais estudos para avaliar o impacto de sua modulação no manejo da anemia nessa população.

Isolation and characterization of Lotus japonicus genes involved in iron and zinc homeostasis

DEFF Research Database (Denmark)

Cvitanich, Cristina; Jensen, Winnie; Sandal, Niels Nørgaard

. Legumes are frequently grown in soil with limited nutrient availability. Plants use finely tuned mechanisms to keep appropriated levels of iron and zinc in each of their organs. Several genes involved in iron and zinc homeostasis have been described in yeast, and a few orthologs have been studied...... in plants. We have used these sequences to search for L. japonicus ESTs and genomic loci that are likely to be involved in iron and zinc metabolism. We have identified sequences corresponding to ferritins, ferric reductases, metal transport proteins of the ZIP family, and cation transporters of the NRAMP......The goal of this project is to find ways to improve the nutritional value of legumes by identifying genes and proteins important for iron and zinc regulation in the model legume Lotus japonicus. Legumes are important staples in the developing world and are a major source of nutrients in many areas...

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.

Iron-induced changes in the proteome of Trichomonas vaginalis hydrogenosomes.

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Neritza Campo Beltrán

Full Text Available Iron plays a crucial role in metabolism as a key component of catalytic and redox cofactors, such as heme or iron-sulfur clusters in enzymes and electron-transporting or regulatory proteins. Limitation of iron availability by the host is also one of the mechanisms involved in immunity. Pathogens must regulate their protein expression according to the iron concentration in their environment and optimize their metabolic pathways in cases of limitation through the availability of respective cofactors. Trichomonas vaginalis, a sexually transmitted pathogen of humans, requires high iron levels for optimal growth. It is an anaerobe that possesses hydrogenosomes, mitochondrion-related organelles that harbor pathways of energy metabolism and iron-sulfur cluster assembly. We analyzed the proteomes of hydrogenosomes obtained from cells cultivated under iron-rich and iron-deficient conditions employing two-dimensional peptide separation combining IEF and nano-HPLC with quantitative MALDI-MS/MS. We identified 179 proteins, of which 58 were differentially expressed. Iron deficiency led to the upregulation of proteins involved in iron-sulfur cluster assembly and the downregulation of enzymes involved in carbohydrate metabolism. Interestingly, iron affected the expression of only some of multiple protein paralogues, whereas the expression of others was iron independent. This finding indicates a stringent regulation of differentially expressed multiple gene copies in response to changes in the availability of exogenous iron.

Importance of boreal rivers in providing iron to marine waters.

Directory of Open Access Journals (Sweden)

Emma S Kritzberg

Full Text Available This study reports increasing iron concentrations in rivers draining into the Baltic Sea. Given the decisive role of iron to the structure and biogeochemical function of aquatic ecosystems, this trend is likely one with far reaching consequences to the receiving system. What those consequences may be depends on the fate of the iron in estuarine mixing. We here assess the stability of riverine iron by mixing water from seven boreal rivers with artificial sea salts. The results show a gradual loss of iron from suspension with increasing salinity. However, the capacity of the different river waters to maintain iron in suspension varied greatly, i.e. between 1 and 54% of iron was in suspension at a salinity of 30. The variability was best explained by iron:organic carbon ratios in the riverine waters--the lower the ratio the more iron remained in suspension. Water with an initially low iron:organic carbon ratio could keep even higher than ambient concentrations of Fe in suspension across the salinity gradient, as shown in experiments with iron amendments. Moreover, there was a positive relationship between the molecular size of the riverine organic matter and the amount of iron in suspension. In all, the results point towards a remarkably high transport capacity of iron from boreal rivers, suggesting that increasing concentrations of iron in river mouths may result in higher concentrations of potentially bioavailable iron in the marine system.

Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.

Science.gov (United States)

Renaud, Stéphanie; Corcé, Vincent; Cannie, Isabelle; Ropert, Martine; Lepage, Sylvie; Loréal, Olivier; Deniaud, David; Gaboriau, François

2015-08-01

Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine chain, is related to its high selectivity for the Polyamine Transport System (PTS), allowing its preferential uptake by tumoral cells. The difference in PTS activation between healthy cells and tumor cells enables tumor cells to be targeted, whereas the strong dependence of these cells on iron ensures a secondary targeting. Here, we demonstrated in vitro that HQ1-44 inhibits DNA synthesis and cell proliferation of HCT116 cells by modulating the intracellular metabolism of both iron and polyamines. Moreover, in vivo, in xenografted athymic nude mice, we found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects. Furthermore, as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ1-44. These data support the need for further studies to assess the value of HQ1-44 as an adjuvant treatment in cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Iron and thiols as two major players in carcinogenesis: friends or foes?

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Toyokuni, Shinya

2014-01-01

Iron is the most abundant metal in the human body and mainly works as a cofactor for proteins such as hemoglobin and various enzymes. No independent life forms on earth can survive without iron. However, excess iron is intimately associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Biomolecules with redox-active sulfhydryl function(s) (thiol compounds) are necessary for the maintenance of mildly reductive cellular environments to counteract oxidative stress, and for the execution of redox reactions for metabolism and detoxification. Involvement of glutathione S-transferase and thioredoxin has long attracted the attention of cancer researchers. Here, I update recent findings on the involvement of iron and thiol compounds during carcinogenesis and in cancer cells. It is now recognized that the cystine/glutamate transporter (antiporter) is intimately associated with ferroptosis, an iron-dependent, non-apoptotic form of cell death, observed in cancer cells, and also with cancer stem cells; the former with transporter blockage but the latter with its stabilization. Excess iron in the presence of oxygen appears the most common known mutagen. Ironically, the persistent activation of antioxidant systems via genetic alterations in Nrf2 and Keap1 also contributes to carcinogenesis. Therefore, it is difficult to conclude the role of iron and thiol compounds as friends or foes, which depends on the quantity/distribution and induction/flexibility, respectively. Avoiding further mutation would be the most helpful strategy for cancer prevention, and myriad of efforts are being made to sort out the weaknesses of cancer cells.

Effect of different iron levels on 65Zn uptake and transport in maize seedlings

International Nuclear Information System (INIS)

Rathore, V.S.; Sharma, D.; Kandala, J.C.

1974-01-01

Uptake and translocation of 65 Zn was studied in two week old maize seedlings at 0.01, 0.1, 1 and 5 ppm iron levels in half-strength Hoagland's solution. Four different zinc levels viz., 0.04, 0.4, 4 and 8 ppm were taken. Total 65 Zn uptake and translocation to shoots at 2, 4, 6 and 12 hours showed that increasing iron levels in the uptake medium reduced Zn-uptake in all combinations and at all uptake hours studied. This antagnnistic effect of iron on zinc uptake was more pronounced at the initial stages and could be partly inhibited by increasing zinc concentration in the uptake medium. Translocation of 65 Zn to shoots increased with increase in uptake time. Increasing iron levels in the medium decreased zinc dislocation to shoots at all zinc levels. (author)

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...

The Structure of the Iron Binding Protein, FutA1, from Synechocystis 6803*

International Nuclear Information System (INIS)

Koropatkin, Nicole; Randich, Amelia M.; Bhattacharyya-Pakrasi, Maitrayee; Pakrasi, Himadri B.; Smith, Thomas J.

2007-01-01

Cyanobacteria account for a significant percentage of aquatic primary productivity even in areas where the concentrations of essential micronutrients are extremely low. To better understand the mechanism of iron selectivity and transport, the structure of the solute-binding domain of an ABC iron transporter, FutA1, was determined in the presence and absence of iron. The iron ion is bound within the 'C-clamp' structure via four tyrosine and one histidine residues. There are extensive interactions between these ligating residues and the rest of the protein such that the conformations of the side chains remain relatively unchanged as the iron is released by the opening of the metal binding cleft. This is in stark contrast to the zinc binding protein, ZnuA, where the domains of the metal binding protein remain relatively fixed while the ligating residues rotate out of the binding pocket upon metal release. The rotation of the domains in FutA1 is facilitated by two flexible β-strands running along the back of the protein that act like a hinge during domain motion. This motion may require relatively little energy since total contact area between the domains is the same whether the protein is in the open or closed conformation. Consistent with the pH dependency of iron binding, the main trigger for iron release is likely the histidine in the iron-binding site. Finally, neither FutA1 nor FutA2 binds iron as a siderophore complex or in the presence of anions and both preferentially bind ferrous over ferric ions

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.

[Cloning and expression analysis of a zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like protein encoding gene in Dendrobium officinale].

Science.gov (United States)

Zhang, Gang; Li, Yi-Min; Li, Biao; Zhang, Da-Wei; Guo, Shun-Xing

2015-01-01

The zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like protein (ZIP) plays an important role in the growth and development of plant. In this study, a full length cDNA of ZIP encoding gene, designed as DoZIP1 (GenBank accession KJ946203), was identified from Dendrobium officinale using RT-PCR and RACE. Bioinformatics analysis showed that DoZIP1 consisted of a 1,056 bp open reading frame (ORF) encoded a 351-aa protein with a molecular weight of 37.57 kDa and an isoelectric point (pI) of 6.09. The deduced DoZIP1 protein contained the conserved ZIP domain, and its secondary structure was composed of 50.71% alpha helix, 11.11% extended strand, 36.18% random coil, and beta turn 1.99%. DoZIP1 protein exhibited a signal peptide and eight transmembrane domains, presumably locating in cell membrane. The amino acid sequence had high homology with ZIP proteins from Arabidopsis, alfalfa and rice. A phylogenetic tree analysis demonstrated that DoZIP1 was closely related to AtZIP10 and OsZIP3, and they were clustered into one clade. Real time quantitative PCR analysis demonstrated that the transcription level of DoZIP1 in D. officinale roots was the highest (4.19 fold higher than that of stems), followed by that of leaves (1.12 fold). Molecular characters of DoZIP1 will be useful for further functional determination of the gene involving in the growth and development of D. officinale.

Volatile compounds from beneficial or pathogenic bacteria differentially regulate root exudation, transcription of iron transporters, and defense signaling pathways in Sorghum bicolor.

Science.gov (United States)

Hernández-Calderón, Erasto; Aviles-Garcia, Maria Elizabeth; Castulo-Rubio, Diana Yazmín; Macías-Rodríguez, Lourdes; Ramírez, Vicente Montejano; Santoyo, Gustavo; López-Bucio, José; Valencia-Cantero, Eduardo

2018-02-01

Our results show that Sorghum bicolor is able to recognize bacteria through its volatile compounds and differentially respond to beneficial or pathogens via eliciting nutritional or defense adaptive traits. Plants establish beneficial, harmful, or neutral relationships with bacteria. Plant growth promoting rhizobacteria (PGPR) emit volatile compounds (VCs), which may act as molecular cues influencing plant development, nutrition, and/or defense. In this study, we compared the effects of VCs produced by bacteria with different lifestyles, including Arthrobacter agilis UMCV2, Bacillus methylotrophicus M4-96, Sinorhizobium meliloti 1021, the plant pathogen Pseudomonas aeruginosa PAO1, and the commensal rhizobacterium Bacillus sp. L2-64, on S. bicolor. We show that VCs from all tested bacteria, except Bacillus sp. L2-64, increased biomass and chlorophyll content, and improved root architecture, but notheworthy A. agilis induced the release of attractant molecules, whereas P. aeruginosa activated the exudation of growth inhibitory compounds by roots. An analysis of the expression of iron-transporters SbIRT1, SbIRT2, SbYS1, and SbYS2 and genes related to plant defense pathways COI1 and PR-1 indicated that beneficial, pathogenic, and commensal bacteria could up-regulate iron transporters, whereas only beneficial and pathogenic species could induce a defense response. These results show how S. bicolor could recognize bacteria through their volatiles profiles and highlight that PGPR or pathogens can elicit nutritional or defensive traits in plants.

Basin scale survey of marine humic fluorescence in the Atlantic: relationship to iron solubility and H2O2

OpenAIRE

Heller, Maija; Gaiero, Diego; Croot, Peter

2013-01-01

Iron (Fe) is a limiting nutrient for phytoplankton productivity in many different oceanic regions. A critical aspect underlying iron limitation is its low solubility in seawater as this controls the distribution and transport of iron through the ocean. Processes which enhance the solubility of iron in seawater, either through redox reactions or organic complexation, are central to understanding the biogeochemical cycling of iron. In this work we combined iron solubility measurements with para...

Heavy metal toxicity and iron chlorosis

Energy Technology Data Exchange (ETDEWEB)

DeKock, P C

1956-01-01

The toxicity of copper, nickel, cobalt, zinc, chromium, and manganese to mustard was studied in water culture, utilizing either the ionic form or the EDTA chelate of the metal in the presence of either ferric chloride or ferric EDTA. In presence of ferric chloride the activity of the metals in producing chlorosis was as given above, i.e. in the order of stability of their chelates. In the presence of ferric versenate, toxicity of the ionic metal was much reduced. The metal chelates gave very little indication of toxicity with either form of iron. It was found that the ratio of total phosphorus to total iron was higher in chlorotic plants than in green plants, irrespective of which metal was causing the toxicity. Copper could be demonstrated in the phloem cells of the root using biscyclohexanone-oxalydihydrazone as histochemical reagent. It is postulated that transport of iron probably takes place in the phloem as an active process. It would appear that as a major part of the iron in plant cells is attached to nucleo- or phospho-proteins, the heavy metals must be similarly attached to phospho-proteins.

Manganese Transport and Toxicity in Polarized WIF-B Hepatocytes.

Science.gov (United States)

Thompson, Khristy J; Hein, Jennifer; Baez, Andrew; Sosa, Jose Carlo; Wessling-Resnick, Marianne

2018-05-24

Mn toxicity arises from nutritional problems, community and occupational exposures, and genetic risks. Mn blood levels are controlled by hepatobiliary clearance. The goals of this study were to determine the cellular distribution of Mn transporters in polarized hepatocytes, to establish an in vitro assay for hepatocyte Mn efflux, and to examine possible roles the Mn transporters would play in metal import and export. For these experiments, hepatocytoma WIF-B cells were grown for 12-14 days to achieve maximal polarity. Immunoblots showed that Mn transporters ZIP8, ZnT10, ferroportin (Fpn), and ZIP14 were present. Indirect immunofluorescence microscopy localized Fpn and ZIP14 to WIF-B cell basolateral domains while ZnT10 and ZIP8 associated with intracellular vesicular compartments. ZIP8-positive structures were distributed uniformly throughout the cytoplasm, but ZnT10-positive vesicles were adjacent to apical bile compartments. WIF-B cells were sensitive to Mn toxicity, showing decreased viability after 16 h exposure to > 250 M MnCl2. However, the hepatocytes were resistant to 4 h exposures of up to 500 M MnCl2 despite 50-fold increased Mn content. Washout experiments showed time-dependent efflux with 80% Mn released after a 4 h chase period. Hepcidin reduced levels of Fpn in WIF-B cells, clearing Fpn from the cell surface, but Mn efflux was unaffected. The secretory inhibitor brefeldin A did block release of Mn from WIF-B cells, suggesting vesicle fusion may be involved in export. These results point to a possible role of ZnT10 to import Mn into vesicles that subsequently fuse with the apical membrane and empty their contents into bile.

Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking.

Science.gov (United States)

White, Robert A; Boydston, Leigh A; Brookshier, Terri R; McNulty, Steven G; Nsumu, Ndona N; Brewer, Brandon P; Blackmore, Krista

2005-12-01

Defects in iron absorption and utilization lead to iron deficiency and anemia. While iron transport by transferrin receptor-mediated endocytosis is well understood, it is not completely clear how iron is transported from the endosome to the mitochondria where heme is synthesized. We undertook a positional cloning project to identify the causative mutation for the hemoglobin-deficit (hbd) mouse mutant, which suffers from a microcytic, hypochromic anemia apparently due to defective iron transport in the endocytosis cycle. As shown by previous studies, reticulocyte iron accumulation in homozygous hbd/hbd mice is deficient despite normal binding of transferrin to its receptor and normal transferrin uptake in the cell. We have identified a strong candidate gene for hbd, Sec15l1, a homologue to yeast SEC15, which encodes a key protein in vesicle docking. The hbd mice have an exon deletion in Sec15l1, which is the first known mutation of a SEC gene homologue in mammals.

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

Science.gov (United States)

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.

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.

Iron, transferrin and myelinogenesis

International Nuclear Information System (INIS)

Sergeant, C.; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F.

2003-01-01

Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport

Nitric oxide and plant iron homeostasis.

Science.gov (United States)

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.

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).

Mechanisms of iron sensing and regulation in the yeast Saccharomyces cerevisiae.

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Martínez-Pastor, María Teresa; Perea-García, Ana; Puig, Sergi

2017-04-01

Iron is a redox active element that functions as an essential cofactor in multiple metabolic pathways, including respiration, DNA synthesis and translation. While indispensable for eukaryotic life, excess iron can lead to oxidative damage of macromolecules. Therefore, living organisms have developed sophisticated strategies to optimally regulate iron acquisition, storage and utilization in response to fluctuations in environmental iron bioavailability. In the yeast Saccharomyces cerevisiae, transcription factors Aft1/Aft2 and Yap5 regulate iron metabolism in response to low and high iron levels, respectively. In addition to producing and assembling iron cofactors, mitochondrial iron-sulfur (Fe/S) cluster biogenesis has emerged as a central player in iron sensing. A mitochondrial signal derived from Fe/S synthesis is exported and converted into an Fe/S cluster that interacts directly with Aft1/Aft2 and Yap5 proteins to regulate their transcriptional function. Various conserved proteins, such as ABC mitochondrial transporter Atm1 and, for Aft1/Aft2, monothiol glutaredoxins Grx3 and Grx4 are implicated in this iron-signaling pathway. The analysis of a wide range of S. cerevisiae strains of different geographical origins and sources has shown that yeast strains adapted to high iron display growth defects under iron-deficient conditions, and highlighted connections that exist in the response to both opposite conditions. Changes in iron accumulation and gene expression profiles suggest differences in the regulation of iron homeostasis genes.

Prevalence of Iron Deficiency and Iron Deficiency Anemia in High-School Girl Students of Yazd

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M Noori Shadkam

2009-07-01

Full Text Available Introduction: It is generally assumed that 50% of the cases of anemia are due to iron deficiency. The most severe consequence of iron depletion is iron deficiency anemia (IDA, and it is still considered the most common nutrition deficiency worldwide. The main risk factors for IDA include: inadequate iron intake, impaired absorption or transport, physiologic losses associated with chronological or reproductive age, or acute or chronic blood loss, parasite infections such as hookworms, acute and chronic infections, including malaria, cancer, tuberculosis, HIV and other micronutrient deficiencies, including vitamins A and B12, folate, riboflavin, and copper deficiency. Methods: This work as a cross-sectional study was done in 2007-2008 in Yazd. Two hundred girls who participated in the study were selected randomly from eight girl high schools. Five ml venous blood was collected for determination of serum ferritin and cell blood count (CBC. Serum ferritin was determined by using ECLIA method and CBC by cell counter SYSMEX KX21N. Iron deficiency was defined as having serum ferritin values below 12 μ/l. Anemia was defined as having Hemoglobin levels below12 g/dl. Iron-deficiency anemia was considered to be the combination of both. Results: The3 mean ageyears and body mass index (kg/m2 were 15.19±0.7years and 21.5±4.2, respectively. Distribution in the 14, 15 and 16 years and more age groups were 13, 58.5 and 28.5 percent, respectively. Mean of Hemoglobin(g/dl, Hematocrit(%, MCV (fl, MCH (pg, MCHC (g/dl and ferritin(μ/l were 12.8±0.9, 38.9±3.0, 80.7±4.3, 26.6±1.8, 33.2±3.6 and 23±18.2, respectively. Of the total, 13.5% were anemic, 68% of which had Iron Deficiency Anemia (9.3% of the total. Iron deficiency was present in 34.7% of the population under study. Conclusion: According to world health organization criteria, anemia is a mild public health problem in this region, but iron deficiency is a significant problem and suitable measures for

EDITORIAL: The electromagnetic properties of iron-based superconductors The electromagnetic properties of iron-based superconductors

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Prozorov, Ruslan; Gurevich, Alex; Luke, Graeme

2010-05-01

cuprates, a superconducting 'dome' is formed upon doping the parent compounds, which exhibits antiferromagnetic and structural transitions at temperatures well above the superconducting critical temperature. This special section touches on several key aspects of these new iron-based superconductors. These topics include materials synthesis and basic characterization, the role of impurities and pairing symmetry, and mapping of the superconducting phase diagram as a function of chemical doping and pressure. Studies of transport, magnetic and optical properties account for a substantial portion of this special section. Particular attention is devoted to the role of magnetic excitations and the issue of the possible coexistence of magnetism and superconductivity. Attempts to understand the nature of the superconducting pairing are discussed from several angles, including tunneling spectroscopy and the London penetration depth. The vortex state is probed by magnetization, transport and neutron scattering, while the irreversible state is probed by studies of magnetic and transport critical current density.

Accumulation and distribution of iron, cadmium, lead and nickel in cucumber plants grown in hydroponics containing two different chelated iron supplies.

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Csog, Árpád; Mihucz, Victor G; Tatár, Eniko; Fodor, Ferenc; Virág, István; Majdik, Cornelia; Záray, Gyula

2011-07-01

Cucumber plants grown in hydroponics containing 10 μM Cd(II), Ni(II) and Pb(II), and iron supplied as Fe(III) EDTA or Fe(III) citrate in identical concentrations, were investigated by total-reflection X-ray fluorescence spectrometry with special emphasis on the determination of iron accumulation and distribution within the different plant compartments (root, stem, cotyledon and leaves). The extent of Cd, Ni and Pb accumulation and distribution were also determined. Generally, iron and heavy-metal contaminant accumulation was higher when Fe(III) citrate was used. The accumulation of nickel and lead was higher by about 20% and 100%, respectively, if the iron supply was Fe(III) citrate. The accumulation of Cd was similar. In the case of Fe(III) citrate, the total amounts of Fe taken up were similar in the control and heavy-metal-treated plants (27-31 μmol/plant). Further, the amounts of iron transported from the root towards the shoot of the control, lead- and nickel-contaminated plants were independent of the iron(III) form. Although Fe mobility could be characterized as being low, its distribution within the shoot was not significantly affected by the heavy metals investigated. Copyright © 2011 Elsevier GmbH. All rights reserved.

The interplay between iron accumulation, mitochondrial dysfunction and inflammation during the execution step of neurodegenerative disorders

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Pamela J. Urrutia

2014-03-01

Full Text Available A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich’s ataxia and Parkinson’s disease. Particularly relevant for neurodegenerative processes is the relationship between mitochondria and iron. The mitochondrion upholds the synthesis of iron-sulfur clusters and heme, the most abundant iron-containing prosthetic groups in a large variety of proteins, so a fraction of incoming iron must go through this organelle before reaching its final destination. In turn, the mitochondrial respiratory chain is the source of reactive oxygen species (ROS derived from leaks in the electron transport chain. The co-existence of both iron and ROS in the secluded space of the mitochondrion makes this organelle particularly prone to hydroxyl radical-mediated damage. In addition, a connection between the loss of iron homeostasis and inflammation is starting to emerge; thus, inflammatory cytokines like TNF-alpha and IL-6 induce the synthesis of the divalent metal transporter 1 and promote iron accumulation in neurons and microglia. Here, we review the recent literature on mitochondrial iron homeostasis and the role of inflammation on mitochondria dysfunction and iron accumulation on the neurodegenerative process that lead to cell death in Parkinson’s disease. We also put forward the hypothesis that mitochondrial dysfunction, iron accumulation and inflammation are part of a synergistic self-feeding cycle that ends in apoptotic cell death, once the antioxidant cellular defense systems are finally overwhelmed.

Identification of genes expressed by Cryptococcus gattii during iron deprivation

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Daphine Ariadne Jesus de Paula

2014-09-01

Full Text Available Cryptococcus neoformans and C. gattii are pathogenic yeasts that cause life-threatening diseases in humans and animals. Iron is an essential nutrient for virtually every organism as it functions as a cofactor in numerous essential enzymatic reactions. In the literature, the competition for iron between microbes and mammalian hosts during infection is well documented. In this study, we used representational difference analysis (RDA in order to gain a better understanding of how C. gattii responds to iron starvation. A total of 15 and 29 genes were identified as having altered expression levels due to iron depletion after 3 h and 12 h, respectively. Of these, eight genes were identified in both libraries. The transcripts were related to many biological processes, such as cell cycle, ergosterol metabolism, cell wall organization, transportation, translation, cell respiration and the stress response. These data suggest a remodeling of C. gattii metabolism during conditions of iron deprivation.

Studies on effect of Microbial Iron Chelators on Candida Albican

International Nuclear Information System (INIS)

Rehmani, Fouzia S.; Milicent, S.; Zaheer-Uddin

2005-01-01

Iron is an essential for the life of all microbe cells. It generally exists in the oxidized form Fe(III). Even under anaerobic reducing condition the metal appear to be taken up as Fe(III). Thus free-living microorganisms require specific and effective ferric ion transport system to cope with low availability of the metal. In iron deficient environment they produce a low molecular weight specific chelators called siderphores or microbial iron chelators. Siderphores compete for limited supplied of iron. These compounds came out of the cell but can not re-enter without iron due to high affinity of these siderphores often have more than one catechol/hydroxamate functions and are multidentate (usually hexadentate ligands). The aim of the present research is to check the effect of iron chelators, namely gallic acid and salisyl hydroxamate on the growth of Candida albican in vitro. C. albican is the opportunistic paltogen present as the normal flora inside human body. In vivo the growth of C. albican is distributed by the use of antibiotics and immuno suppressers. In cases of iron over-dosage in human being, the patients are treated with certain a-iron chelators. Hence an attempt is made to notice the effect that might be inhibition or enhancement of the organism in vitro. (author)

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

Interdependence between iron ore production and maritime transport

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A. V. Todorut

2016-10-01

Full Text Available The maritime industry plays an important role in international trade, transporting a total of 10,1 billion tons of merchandise in 2015, representing over 80% of all global trade, with dry cargo estimated to account for over two thirds of the total seaborne trade. Bulk carriers supply the raw materials needed by the steel industry and container ships transport the steel products. Demand and supply for seaborne transport is influenced by trends in global economy and worldwide demand for commodities. The paper analyzes the most important economic determinants in the supply of metallurgical raw materials, highlighting the importance of the shipping sector.

Shelf-to-basin iron shuttling enhances vivianite formation in deep Baltic Sea sediments

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Reed, Daniel C.; Gustafsson, Bo G.; Slomp, Caroline P.

2016-01-01

Coastal hypoxia is a growing and persistent problem largely attributable to enhanced terrestrial nutrient (i.e., nitrogen and phosphorus) loading. Recent studies suggest phosphorus removal through burial of iron (II) phosphates, putatively vivianite, plays an important role in nutrient cycling in the Baltic Sea - the world's largest anthropogenic dead zone - yet the dynamics of iron (II) phosphate formation are poorly constrained. To address this, a reactive-transport model was used to reconstruct the diagenetic and depositional history of sediments in the Fårö basin, a deep anoxic and sulphidic region of the Baltic Sea where iron (II) phosphates have been observed. Simulations demonstrate that transport of iron from shelf sediments to deep basins enhances vivianite formation while sulphide concentrations are low, but that pyrite forms preferentially over vivianite when sulphate reduction intensifies due to elevated organic loading. Episodic reoxygenation events, associated with major inflows of oxic waters, encourage the retention of iron oxyhydroxides and iron-bound phosphorus in sediments, increasing vivianite precipitation as a result. Results suggest that artificial reoxygenation of the Baltic Sea bottom waters could sequester up to 3% of the annual external phosphorus loads as iron (II) phosphates, but this is negligible when compared to potential internal phosphorus loads due to dissolution of iron oxyhydroxides when low oxygen conditions prevail. Thus, enhancing vivianite formation through artificial reoxygenation of deep waters is not a viable engineering solution to eutrophication in the Baltic Sea. Finally, simulations suggest that regions with limited sulphate reduction and hypoxic intervals, such as eutrophic estuaries, could act as important phosphorus sinks by sequestering vivianite. This could potentially alleviate eutrophication in shelf and slope environments.

Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

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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

Electron transport chain dysfunction by H(2)O (2) is linked to increased reactive oxygen species production and iron mobilization by lipoperoxidation: studies using Saccharomyces cerevisiae mitochondria.

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Cortés-Rojo, Christian; Estrada-Villagómez, Mirella; Calderón-Cortés, Elizabeth; Clemente-Guerrero, Mónica; Mejía-Zepeda, Ricardo; Boldogh, Istvan; Saavedra-Molina, Alfredo

2011-04-01

The mitochondrial electron transport chain (ETC) contains thiol groups (-SH) which are reversibly oxidized to modulate ETC function during H(2)O(2) overproduction. Since deleterious effects of H(2)O(2) are not limited to -SH oxidation, due to the formation of other H(2)O(2)-derived species, some processes like lipoperoxidation could enhance the effects of H(2)O(2) over ETC enzymes, disrupt their modulation by -SH oxidation and increase superoxide production. To verify this hypothesis, we tested the effects of H(2)O(2) on ETC activities, superoxide production and iron mobilization in mitochondria from lipoperoxidation-resistant native yeast and lipoperoxidation-sensitized yeast. Only complex III activity from lipoperoxidation-sensitive mitochondria exhibited a higher susceptibility to H(2)O(2) and increased superoxide production. The recovery of ETC activity by the thiol reductanct β-mercaptoethanol (BME) was also altered at complex III, and a role was attributed to lipoperoxidation, the latter being also responsible for iron release. A hypothetical model linking lipoperoxidation, increased complex III damage, superoxide production and iron release is given.

Iron persistence in a distal hydrothermal plume supported by dissolved-particulate exchange

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Fitzsimmons, Jessica N.; John, Seth G.; Marsay, Christopher M.; Hoffman, Colleen L.; Nicholas, Sarah L.; Toner, Brandy M.; German, Christopher R.; Sherrell, Robert M.

2017-02-01

Hydrothermally sourced dissolved metals have been recorded in all ocean basins. In the oceans' largest known hydrothermal plume, extending westwards across the Pacific from the Southern East Pacific Rise, dissolved iron and manganese were shown by the GEOTRACES program to be transported halfway across the Pacific. Here, we report that particulate iron and manganese in the same plume also exceed background concentrations, even 4,000 km from the vent source. Both dissolved and particulate iron deepen by more than 350 m relative to 3He--a non-reactive tracer of hydrothermal input--crossing isopycnals. Manganese shows no similar descent. Individual plume particle analyses indicate that particulate iron occurs within low-density organic matrices, consistent with its slow sinking rate of 5-10 m yr-1. Chemical speciation and isotopic composition analyses reveal that particulate iron consists of Fe(III) oxyhydroxides, whereas dissolved iron consists of nanoparticulate Fe(III) oxyhydroxides and an organically complexed iron phase. The descent of plume-dissolved iron is best explained by reversible exchange onto slowly sinking particles, probably mediated by organic compounds binding iron. We suggest that in ocean regimes with high particulate iron loadings, dissolved iron fluxes may depend on the balance between stabilization in the dissolved phase and the reversibility of exchange onto sinking particles.

Genetics Home Reference: iron-refractory iron deficiency anemia

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... 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 ...

Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

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Harold Tjalsma

Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

The influence of high iron diet on rat lung manganese absorption

International Nuclear Information System (INIS)

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

Electrochemically controlled iron isotope fractionation

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Black, Jay R.; Young, Edward D.; Kavner, Abby

2010-02-01

Variations in the stable isotope abundances of transition metals have been observed in the geologic record and trying to understand and reconstruct the physical/environmental conditions that produced these signatures is an area of active research. It is clear that changes in oxidation state lead to large fractionations of the stable isotopes of many transition metals such as iron, suggesting that transition metal stable isotope signatures could be used as a paleo-redox proxy. However, the factors contributing to these observed stable isotope variations are poorly understood. Here we investigate how the kinetics of iron redox electrochemistry generates isotope fractionation. Through a combination of electrodeposition experiments and modeling of electrochemical processes including mass-transport, we show that electron transfer reactions are the cause of a large isotope separation, while mass transport-limited supply of reactant to the electrode attenuates the observed isotopic fractionation. Furthermore, the stable isotope composition of electroplated transition metals can be tuned in the laboratory by controlling parameters such as solution chemistry, reaction overpotential, and solution convection. These methods are potentially useful for generating isotopically-marked metal surfaces for tracking and forensic purposes. In addition, our studies will help interpret stable isotope data in terms of identifying underlying electron transfer processes in laboratory and natural samples.

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

Iron, transferrin and myelinogenesis

Energy Technology Data Exchange (ETDEWEB)

Sergeant, C. E-mail: sergeant@cenbg.in2p3.fr; Vesvres, M.H.; Deves, G.; Baron, B.; Guillou, F

2003-09-01

Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5{sup '} and 3{sup '} untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

Study on Increasing High Temperature pH(t) to Reduce Iron Corrosion Products

International Nuclear Information System (INIS)

Shin, Dong Man; Hur, Nam Yong; Kim, Waang Bae

2011-01-01

The transportation and deposition of iron corrosion products are important elements that affect both the steam generator (SG) integrity and secondary system in pressurized water reactor (PWR) nuclear power plants. Most of iron corrosion products are generated on carbon steel materials due to flow accelerated corrosion (FAC). The several parameters like water chemistry, temperature, hydrodynamic, and steel composition affect FAC. It is well established that the at-temperature pH of the deaerated water system has a first order effect on the FAC rate of carbon steels through nuclear industry researches. In order to reduce transportation and deposition of iron corrosion products, increasing pH(t) tests were applied on secondary system of A, B units. Increasing pH(t) successfully reduced flow accelerated corrosion. The effect of increasing pH(t) to inhibit FAC was identified through the experiment and pH(t) evaluation in this paper

The Effects of Dietary Calcium and/or Iron Deficiency upon Murine Intestinal Calcium Binding Protein Activity and Calcium Absorption

OpenAIRE

McDonald, Catherine M.

1980-01-01

Iron deficiency has been shown to impair calcium absorption, leading to decreased bone mass. Vitamin D3-dependent calcium binding protein (CaBP) has been demonstrated to be necessary for the active transport of calcium in the intestine of numerous species. Iron deficiency might affect the activity of the calcium binding protein. Four experimental diets were formulated as follows: Diet 1, iron adequate, calcium adequate; Diet 2, iron deficient, calcium adequate; Diet 3, iron adequate, calci...

Calculation of parameters for an iron shield experiment

International Nuclear Information System (INIS)

Gavazza, S.

1986-01-01

In this text is carreid out the evaluation of radiation transport methodology, comparying the calculated reactions and dose rates, for neutrons and gama-rays, with the experimental measurements obtained on iron shield, irradiated in YAYOI reactor. Were employed the ENDF/B-IV and VITAMIN-C libraries and the AMPX-II modular system for generation of cross sections, collapsed by the ANISN code. The tranpsort calculations were made by using the DOT 3.5 code, adjusting the spectrum of the iron shield boundary source to the reaction and doses rates, measured at the beginning of shield. The distributions calculated for neutrons and gamma-rays, on iron shield, presented reasonable concordance with the experimental measurements. Finally, is presented a proposal for setting up of an experimental arrangement, using the IEA-R1 reactor, with the purpose of lay down a shielding benchmark. (Author) [pt

Route planning of raw materials transportation in the industrial hub of Mariupol city

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Юлія Вікторівна Булгакова

2017-07-01

Full Text Available The multi-modal freight transportation routes planning problem is viewed in this paper. The case study of iron ore deliveries to the metallurgical enterprises of Mariupol from Kryvyi Rih is presented. Based on the analysis of Ukrainian railroads and sea ports infrastructures six possible routes of multi-modal iron ore transportation are built. The paper presents a short review of route planning problem in multi-modal freight transportations, which are use sea and land parts together, regarding decision support methods of routes evaluation and selection. The lack of studies dedicated to fuzzy logic theory application for solving the stated problems is identified. The relevance of fuzzy set application to the route planning problem is proved. Taking into account the peculiarities of iron ore transportations technology, the following criterions of routes evaluation are chosen: «transportation costs», «delivery times», «transportation risks». The model of multicriterion decision-making of routes evaluation and the optimal route selection, based on fuzzy logic theory, is developed. Criteria of routes evaluation are set by three terms Gaussian and sigmoidal membership functions. The approach to each function construction is practice-based and executed together with iron ore supply chain manager. The model is created in MATLAB Fuzzy Logic Tool Box environment using Mamdani’s fuzzy inference

CHARACTERIZATION OF METAL GRADES IN A STOCKPILE OF AN IRON MINE (CASE STUDY- CHOGHART IRON MINE, IRAN

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Francesco Tinti

2018-01-01

Full Text Available In any mining operation due to the cut-off grade (economic criteria, materials classify into the ore and waste. The material with grade equal to or higher than the cut-off grade is considered as ore and the material with grade less than the cut-off grade is transported as wastes to the waste dumps. However, because of increasing metal demand, depleting of in situ ore reserves and so the reduction of cut-off grades for many metals, the mentioned waste dumps were considered as valuable ore reserves named stockpiles. In this paper, multivariate geostatistics was used to estimate the iron grades of two stockpiles following the sequential of piling procedures from the main source - the ore deposit - to the piling field. One stockpile is characterized by phosphorous concentration ((P % > 0.6 %, while the other by iron concentration ((Fe %< 50%. Since economic and physical constraints made sampling physically and economically problematic, the grade distribution and variability were estimated on the basis of primary blast-hole data from the main ore body and the mine’s long-term planning policy. A geostatistical model was applied to the excavated part of the iron deposit and the stockpile, by reconstructing ore selection, haulage and piling method. Results were validated through spatial variability of iron and phosphorous concentrations by comparing grade variability (Fe and P with mining and pilling units. This methodology allows characterizing the iron grades within stockpiles without any extra sampling.

Effects of sulfate on heavy metal release from iron corrosion scales in drinking water distribution system.

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Sun, Huifang; Shi, Baoyou; Yang, Fan; Wang, Dongsheng

2017-05-01

Trace heavy metals accumulated in iron corrosion scales within a drinking water distribution system (DWDS) could potentially be released to bulk water and consequently deteriorate the tap water quality. The objective of this study was to identify and evaluate the release of trace heavy metals in DWDS under changing source water conditions. Experimental pipe loops with different iron corrosion scales were set up to simulate the actual DWDS. The effects of sulfate levels on heavy metal release were systemically investigated. Heavy metal releases of Mn, Ni, Cu, Pb, Cr and As could be rapidly triggered by sulfate addition but the releases slowly decreased over time. Heavy metal release was more severe in pipes transporting groundwater (GW) than in pipes transporting surface water (SW). There were strong positive correlations (R 2  > 0.8) between the releases of Fe and Mn, Fe and Ni, Fe and Cu, and Fe and Pb. When switching to higher sulfate water, iron corrosion scales in all pipe loops tended to be more stable (especially in pipes transporting GW), with a larger proportion of stable constituents (mainly Fe 3 O 4 ) and fewer unstable compounds (β-FeOOH, γ-FeOOH, FeCO 3 and amorphous iron oxides). The main functional iron reducing bacteria (IRB) communities were favorable for the formation of Fe 3 O 4 . The transformation of corrosion scales and the growth of sulfate reducing bacteria (SRB) accounted for the gradually reduced heavy metal release with time. The higher metal release in pipes transporting GW could be due to increased Fe 6 (OH) 12 CO 3 content under higher sulfate concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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 supplementation decreases severity of allergic inflammation in murine lung.

Directory of Open Access Journals (Sweden)

Laura P Hale

Full Text Available The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans.

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.)

The properties and transport phenomena in oxide films on iron, nickel, chromium and their alloys in aqueous environments

International Nuclear Information System (INIS)

Laitinen, T.; Bojinov, M.; Betova, I.; Maekelae, K.; Saario, T.

1999-01-01

The construction materials used in coolant systems in nuclear power plants become covered with oxide films as a result of exposure to the aqueous environment. The susceptibility of the materials to different forms of corrosion, as well as the extent of the incorporation of radioactive species on the surfaces of the primary circuit, are greatly influenced by the physical and chemical properties of these oxide films. The composition and characteristics of the oxide films in turn depend on the applied water chemistry. This work was undertaken in order to collect and evaluate the present views on the structure and behaviour of oxide films formed on iron- and nickel-based materials in aqueous environments. This survey should serve to recognise the areas in which more understanding and research effort is needed. The review begins with a discussion on the bulk oxides of iron, nickel and chromium, as well as their mixed oxides. In addition to bulk oxides, the structure and properties of oxide films forming on pure iron, nickel and chromium and on iron- and nickel-based engineering alloys are considered. General approaches to model the structure and growth of oxide films on metals are discussed in detail. The specific features of the oxide structures, properties and growth at high temperatures are presented with special focus on the relevance of existing models. Finally, the role of oxide films in localised corrosion, oxide breakdown pitting. Stress corrosion cracking and related phenomena is considered. The films formed on the surfaces of iron- and nickel-based alloys in high-temperature aqueous environments generally comprise two layers, i.e. the so-called duplex structure. The inner part is normally enriched in chromium and has a more compact structure, while the outer part is enriched in iron and has a cracked or porous structure. The information collected clearly indicates the effect of the chemical environment on the properties of oxide films growing on metal surfaces

The properties and transport phenomena in oxide films on iron, nickel, chromium and their alloys in aqueous environments

Energy Technology Data Exchange (ETDEWEB)

Laitinen, T.; Bojinov, M.; Betova, I.; Maekelae, K.; Saario, T. [VTT Manufacturing Technology, Espoo (Finland)

1999-01-01

The construction materials used in coolant systems in nuclear power plants become covered with oxide films as a result of exposure to the aqueous environment. The susceptibility of the materials to different forms of corrosion, as well as the extent of the incorporation of radioactive species on the surfaces of the primary circuit, are greatly influenced by the physical and chemical properties of these oxide films. The composition and characteristics of the oxide films in turn depend on the applied water chemistry. This work was undertaken in order to collect and evaluate the present views on the structure and behaviour of oxide films formed on iron- and nickel-based materials in aqueous environments. This survey should serve to recognise the areas in which more understanding and research effort is needed. The review begins with a discussion on the bulk oxides of iron, nickel and chromium, as well as their mixed oxides. In addition to bulk oxides, the structure and properties of oxide films forming on pure iron, nickel and chromium and on iron- and nickel-based engineering alloys are considered. General approaches to model the structure and growth of oxide films on metals are discussed in detail. The specific features of the oxide structures, properties and growth at high temperatures are presented with special focus on the relevance of existing models. Finally, the role of oxide films in localised corrosion, oxide breakdown pitting. Stress corrosion cracking and related phenomena is considered. The films formed on the surfaces of iron- and nickel-based alloys in high-temperature aqueous environments generally comprise two layers, i.e. the so-called duplex structure. The inner part is normally enriched in chromium and has a more compact structure, while the outer part is enriched in iron and has a cracked or porous structure. The information collected clearly indicates the effect of the chemical environment on the properties of oxide films growing on metal surfaces

Factors Affecting Ballability of Mixture Iron Ore Concentrates and Iron Oxide Bearing Wastes in Metallurgical Processing

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Mfon Udo

2018-05-01

Full Text Available Iron oxide bearing wastes (IROBEWAS are produced at every segment of processing stage of sinter, molten iron and steel production. They are hard to handle and in many cases are stockpiled only to be a source of environmental pollution but can be balled into pellets. Pellet of good ballability values are transportable and recyclable as they can withstand stress they will encounter without disintegrating back to dust. But ballability is affected by some factors like the grain sizes of the materials, the moisture and binder contents of the ball mix, wettability of the balled materials and the processing perimeters of the granulator. The objective of this research work is to investigate the factors affecting ballability of mixture of iron ore concentrates and iron oxide bearing wastes (IROBEWAS in metallurgical processing. The parameters under consideration were grain size of materials, the moisture contents, the speed of balling disc, IROBEWAS and Bentonite (Binder contents of the balled mix. This was carried out by balling different volume fractions of mix containing iron oxide concentrate and IROBEWAS using a balling disc and testing the resulting balls for green compressive strength using universal testing machine. It was found that the ballability of the mixture of iron ore concentrate and IROBEWAS increases as grain sizes of the materials reduce but increases as the moisture contents and IROBEWAS content increase up to an optimum value of moisture content in the mix before it starts to reduce. The ballability also increases as the speed of the granulator (Balling disc increases within the limit of this work. It was also observed that there was an increase in ballability with slight increase in bentonite content in the mix.

Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog.

Science.gov (United States)

Lo, Miranda; Murray, Gerald L; Khoo, Chen Ai; Haake, David A; Zuerner, Richard L; Adler, Ben

2010-11-01

Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur homologs; we have constructed a mutation in one of these, la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects of la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyte L. biflexa and which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis of la1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, the la1857 mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.

Understanding the Transport of Patagonian Dust and Its Influence on Marine Biological Activity in the South Atlantic Ocean

Science.gov (United States)

Johnson, Matthew; Meskhidze, Nicholas; Kiliyanpilakkil, Praju; Gasso, Santiago

2010-01-01

Modeling and remote sensing techniques were applied to examine the horizontal and vertical transport pathways of Patagonian dust and quantify the effect of soluble-iron- laden mineral dust deposition on marine primary productivity in the South Atlantic Ocean (SAO) surface waters. The global chemistry transport model GEOS-Chem, implemented with an iron dissolution scheme, was applied to evaluate the atmospheric transport and deposition of mineral dust and bioavailable iron during two dust outbreaks originating in the source regions of Patagonia. In addition to this "rapidly released" iron, offline calculations were also carried out to estimate the amount of bioavailable iron leached during the residence time of dust in the ocean mixed layer. Model simulations showed that the horizontal and vertical transport pathways of Patagonian dust plumes were largely influenced by the synoptic meteorological patterns of high and low pressure systems. Model-predicted horizontal and vertical transport pathways of Patagonian dust over the SAO were in reasonable agreement with remotely-sensed data. Comparison between remotely-sensed and offline calculated ocean surface chlorophyll-a concentrations indicated that, for the two dust outbreaks examined in this study, the deposition of bioavailable iron in the SAO through atmospheric pathways was insignificant. As the two dust transport episodes examined here represent typical outflows of mineral dust from South American sources, our study suggests that the atmospheric deposition of mineral dust is unlikely to induce large scale marine primary productivity and carbon sequestration in the South Atlantic sector of the Southern Ocean.

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.

Moléculas que participan en el transporte de hierro materno-fetal: importancia del receptor 1 de transferrina y de la ferroportina en la placenta humana = Molecules implicated in maternal-fetal iron transport across the placental barrier: Role of Transferrin Receptor 1 and Ferroportin

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Corrales Agudelo, Lady Vanessa

2011-03-01

Full Text Available La adecuada transferencia placentaria de hierro es crucial para satisfacer los altos requerimientos del feto y promover su adecuado crecimiento y desarrollo intrauterino; de otra parte, contribuye a prevenir la ferropenia y la anemia, entidades altamente prevalentes en los lactantes durante los primeros dos años de edad, que se asocian con mayor morbilidad y mortalidad en la infancia. La placenta es un órgano capaz de realizar diferentes adaptaciones en la producción de moléculas que participan en el transporte de hierro materno-fetal en respuesta al estado de hierro celular, para proveer la mayor disponibilidad de este mineral al feto. Esta revisión, pretende acercar al lector a los mecanismos metabólicos y moleculares relacionados con la captación, el transporte y la salida de hierro por la placenta hacia el feto, así como su regulación, para proporcionar elementos que le permitan comprender en forma integrada, la importancia de un adecuado estado de hierro materno antes y durante la gestación.

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.

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...

Importance of Ekman transport and gyre circulation change on seasonal variation of surface dissolved iron in the western subarctic North Pacific

Science.gov (United States)

Nakanowatari, Takuya; Nakamura, Tomohiro; Uchimoto, Keisuke; Nishioka, Jun; Mitsudera, Humio; Wakatsuchi, Masaaki

2017-05-01

Iron (Fe) is an essential nutrient for marine phytoplankton and it constitutes an important element in the marine carbon cycle in the ocean. This study examined the mechanisms controlling seasonal variation of dissolved Fe (dFe) in the western subarctic North Pacific (WSNP), using an ocean general circulation model coupled with a simple biogeochemical model incorporating a dFe cycle fed by two major sources (atmospheric dust and continental shelf sediment). The model reproduced the seasonal cycle of observed concentrations of dFe and macronutrients at the surface in the Oyashio region with maxima in winter (February-March) and minima in summer (July-September), although the simulated seasonal amplitudes are a half of the observed values. Analysis of the mixed-layer dFe budget indicated that both local vertical entrainment and lateral advection are primary contributors to the wintertime increase in dFe concentration. In early winter, strengthened northwesterly winds excite southward Ekman transport and Ekman upwelling over the western subarctic gyre, transporting dFe-rich water southward. In mid to late winter, the southward western boundary current of the subarctic gyre and the outflow from the Sea of Okhotsk also bring dFe-rich water to the Oyashio region. The contribution of atmospheric dust to the dFe budget is several times smaller than these ocean transport processes in winter. These results suggest that the westerly wind-induced Ekman transport and gyre circulation systematically influence the seasonal cycle of WSNP surface dFe concentration.

Binding of tryptophan and iron by reptilion plasnna proteins

African Journals Online (AJOL)

transport functions. Albumin of the alligator (Alligator mississippiensis) and other reptiles binds, amongst other ions, tryptophan (McMenamy & Watson 1968) and transferrin binds iron (Barber & Sheeler 1963). Multiple transferrins are present in the plasma of many reptiles. (Dessauer et af 1962) and the albumin region of the.

Higher iron bioavailability of a human-like collagen iron complex.

Science.gov (United States)

Zhu, Chenhui; Yang, Fan; Fan, Daidi; Wang, Ya; Yu, Yuanyuan

2017-07-01

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO 4 , ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO 4 , ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future.

Electron small polarons and their mobility in iron (oxyhydr)oxide nanoparticles

DEFF Research Database (Denmark)

Katz, Jordan E; Zhang, Xiaoyi; Attenkofer, Klaus

2012-01-01

Electron mobility within iron (oxyhydr)oxides enables charge transfer between widely separated surface sites. There is increasing evidence that this internal conduction influences the rates of interfacial reactions and the outcomes of redox-driven phase transformations of environmental interest....... To determine the links between crystal structure and charge-transport efficiency, we used pump-probe spectroscopy to study the dynamics of electrons introduced into iron(III) (oxyhydr)oxide nanoparticles via ultrafast interfacial electron transfer. Using time-resolved x-ray spectroscopy and ab initio...

Control of intracellular heme levels: Heme transporters and Heme oxygenases

Science.gov (United States)

Khan, Anwar A.; Quigley, John G.

2011-01-01

Heme serves as a co-factor in proteins involved in fundamental biological processes including oxidative metabolism, oxygen storage and transport, signal transduction and drug metabolism. In addition, heme is important for systemic iron homeostasis in mammals. Heme has important regulatory roles in cell biology, yet excessive levels of intracellular heme are toxic; thus, mechanisms have evolved to control the acquisition, synthesis, catabolism and expulsion of cellular heme. Recently, a number of transporters of heme and heme synthesis intermediates have been described. Here we review aspects of heme metabolism and discuss our current understanding of heme transporters, with emphasis on the function of the cell-surface heme exporter, FLVCR. Knockdown of Flvcr in mice leads to both defective erythropoiesis and disturbed systemic iron homeostasis, underscoring the critical role of heme transporters in mammalian physiology. PMID:21238504

Investigation of friction and wear characteristics of cast iron material under various conditions

Energy Technology Data Exchange (ETDEWEB)

Joo, Ji Hoon; Kim, Chang Lae; Oh, Jeong Taek; Kim, Dae Eun [Yonsei University, Seoul (Korea, Republic of); Nemati, Narguess [School of Materials and Metallurgy, University of Tehran, Tehran (Iran, Islamic Republic of)

2015-08-15

Cast iron is widely used in fields such as the transport and heavy industries. For parts where contact damage is expected to occur, it is necessary to understand the friction and wear characteristics of cast iron. In this study, we use cast iron plates as the specimens to investigate their friction and wear characteristics. We perform various experiments using a reciprocating type tribotester. We assess the frictional characteristics by analyzing the friction coefficient values that were obtained during the sliding tests. We observe the wear surfaces of cast iron and steel balls using a scanning electron microscope, confocal microscope, and 3D profiler. We investigate the friction and wear characteristics of cast iron by injecting sand and alumina particles having various sizes. Furthermore, we estimate the effect of temperature on the friction and wear characteristics. The results obtained are expected to aid in the understanding of the tribological characteristics of cast iron in industry.

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

Cast iron - a predictable material

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Jorg C. Sturm

2011-02-01

Full Text Available High strength compacted graphite iron (CGI or alloyed cast iron components are substituting previously used non-ferrous castings in automotive power train applications. The mechanical engineering industry has recognized the value in substituting forged or welded structures with stiff and light-weight cast iron castings. New products such as wind turbines have opened new markets for an entire suite of highly reliable ductile iron cast components. During the last 20 years, casting process simulation has developed from predicting hot spots and solidification to an integral assessment tool for foundries for the entire manufacturing route of castings. The support of the feeding related layout of the casting is still one of the most important duties for casting process simulation. Depending on the alloy poured, different feeding behaviors and self-feeding capabilities need to be considered to provide a defect free casting. Therefore, it is not enough to base the prediction of shrinkage defects solely on hot spots derived from temperature fields. To be able to quantitatively predict these defects, solidification simulation had to be combined with density and mass transport calculations, in order to evaluate the impact of the solidification morphology on the feeding behavior as well as to consider alloy dependent feeding ranges. For cast iron foundries, the use of casting process simulation has become an important instrument to predict the robustness and reliability of their processes, especially since the influence of alloying elements, melting practice and metallurgy need to be considered to quantify the special shrinkage and solidification behavior of cast iron. This allows the prediction of local structures, phases and ultimately the local mechanical properties of cast irons, to asses casting quality in the foundry but also to make use of this quantitative information during design of the casting. Casting quality issues related to thermally driven

Transport containers for radioactive material

International Nuclear Information System (INIS)

Bibby, D.

1978-01-01

A transport container for transporting irradiated nuclear fuel is described comprising a steel flask with detachable cover and having external heat exchange fins. The flask contains a solid annular shield comprised of discrete bodies of Pb or Fe bonded together by a solid matrix, for attenuating gamma rays and neutron emission. This may comprise lead shot bonded together by concrete or polyethylene, or alternatively iron shot bonded by concrete. (UK)

Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat.

Directory of Open Access Journals (Sweden)

Angelina Swali

Full Text Available Poor iron status is a global health issue, affecting two thirds of the world population to some degree. It is a particular problem among pregnant women, in both developed and developing countries. Feeding pregnant rats a diet deficient in iron is associated with both hypertension and reduced nephron endowment in adult male offspring. However, the mechanistic pathway leading from iron deficiency to fetal kidney development remains elusive. This study aimed to establish the underlying processes associated with iron deficiency by assessing gene and protein expression changes in the rat embryo, focussing on the responses occurring at the time of the nutritional insult. Analysis of microarray data showed that iron deficiency in utero resulted in the significant up-regulation of 979 genes and down-regulation of 1545 genes in male rat embryos (d13. Affected processes associated with these genes included the initiation of mitosis, BAD-mediated apoptosis, the assembly of RNA polymerase II preinitiation complexes and WNT signalling. Proteomic analyses highlighted 7 proteins demonstrating significant up-regulation with iron deficiency and the down-regulation of 11 proteins. The main functions of these key proteins included cell proliferation, protein transport and folding, cytoskeletal remodelling and the proteasome complex. In line with our recent work, which identified the perturbation of the proteasome complex as a generalised response to in utero malnutrition, we propose that iron deficiency alone leads to a more specific failure in correct protein folding and transport. Such an imbalance in this delicate quality-control system can lead to cellular dysfunction and apoptosis. Therefore these findings offer an insight into the underlying mechanisms associated with the development of the embryo during conditions of poor iron status, and its health in adult life.

Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis

International Nuclear Information System (INIS)

Laskey, J.; Webb, I.; Schulman, H.M.; Ponka, P.

1988-01-01

Transferrin is essential for cell proliferation and it was suggested that it may trigger a proliferative response following its interaction with receptors, serving as a growth factor. However, since the only clearly defined function of transferrin is iron transport, it may merely serve as an iron donor. To further clarify this issue, the authors took advantage of an iron chelate, ferric salicylaldehyde isonicotinoyl hydrazone (Fe-SIH), which they developed and previously demonstrated to efficiently supply iron to cells without using physiological transferrin receptor pathway. As expected, they observed that blocking monoclonal antibodies against transferrin receptors inhibited proliferation of both Raji and murine erythroleukemia cells. This inhibited cell growth was rescued upon the addition of Fe-SIH which was also shown to deliver iron to Raji cells in the presence of blocking anti-transferrin receptor antibodies. Moreover, blocking anti-transferrin receptor antibodies inhibited [ 3 H]thymidine incorporation into DNA and this inhibition could be overcome by added Fe-SIH. In addition, Fe-SIH slightly stimulated, while SIH (an iron chelator) significantly inhibited, DNA synthesis in phytohemagglutinin-stimulated peripheral blood lymphocytes. Taken together, these results indicate that the only function of transferrin supporting cell proliferation is to supply cells with iron

Iron

Science.gov (United States)

Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

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

Directory of Open Access Journals (Sweden)

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.

HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.

Science.gov (United States)

Kaczorowska-Hac, Barbara; Luszczyk, Marcin; Antosiewicz, Jedrzej; Ziolkowski, Wieslaw; Adamkiewicz-Drozynska, Elzbieta; Mysliwiec, Malgorzata; Milosz, Ewa; Kaczor, Jan J

2017-07-01

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

Dietary iron intake, iron status, and gestational diabetes.

Science.gov (United States)

Zhang, Cuilin; Rawal, Shristi

2017-12-01

Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM. © 2017 American Society for Nutrition.

Studies on the pathogenesis in iron deficiency anemia Part 1. Urinary iron excretion in iron deficiency anemia patients and rats in various iron states

OpenAIRE

中西,徳彦

1991-01-01

In the "iron excretion test" , urinary iron excretion after injection of saccharated iron oxide has been reported to be accelerated in relapsing idiopathic iron deficiency anemia. To determine the relevance of urinary iron excretion to clinical factors other than iron metabolism, 15 clinical parameters were evaluated. The serum creatinine level was positively and the serum albumin level was negatively correlated with urinary iron excretion, showing coefficients of r＝0.97,－0.86 respectively, a...

Oncoidal granular iron formation in the Mesoarchaean Pongola Supergroup, southern Africa: Textural and geochemical evidence for biological activity during iron deposition.

Science.gov (United States)

Smith, A J B; Beukes, N J; Gutzmer, J; Czaja, A D; Johnson, C M; Nhleko, N

2017-11-01

We document the discovery of the first granular iron formation (GIF) of Archaean age and present textural and geochemical results that suggest these formed through microbial iron oxidation. The GIF occurs in the Nconga Formation of the ca. 3.0-2.8 Ga Pongola Supergroup in South Africa and Swaziland. It is interbedded with oxide and silicate facies micritic iron formation (MIF). There is a strong textural control on iron mineralization in the GIF not observed in the associated MIF. The GIF is marked by oncoids with chert cores surrounded by magnetite and calcite rims. These rims show laminated domal textures, similar in appearance to microstromatolites. The GIF is enriched in silica and depleted in Fe relative to the interbedded MIF. Very low Al and trace element contents in the GIF indicate that chemically precipitated chert was reworked above wave base into granules in an environment devoid of siliciclastic input. Microbially mediated iron precipitation resulted in the formation of irregular, domal rims around the chert granules. During storm surges, oncoids were transported and deposited in deeper water environments. Textural features, along with positive δ 56 Fe values in magnetite, suggest that iron precipitation occurred through incomplete oxidation of hydrothermal Fe 2+ by iron-oxidizing bacteria. The initial Fe 3+ -oxyhydroxide precipitates were then post-depositionally transformed to magnetite. Comparison of the Fe isotope compositions of the oncoidal GIF with those reported for the interbedded deeper water iron formation (IF) illustrates that the Fe 2+ pathways and sources for these units were distinct. It is suggested that the deeper water IF was deposited from the evolved margin of a buoyant Fe 2+ aq -rich hydrothermal plume distal to its source. In contrast, oncolitic magnetite rims of chert granules were sourced from ambient Fe 2+ aq -depleted shallow ocean water beyond the plume. © 2017 John Wiley & Sons Ltd.

Calculations of the spectra of fast neutrons in iron spheres using the vitamin-C file

International Nuclear Information System (INIS)

Ahmed, F.; Aizawa, O.; Kadotani, H.

1984-01-01

Steady-state space-dependent fast neutron angular and scalar spectra and total flux in various iron spheres have been calculated using the one-dimensional discrete ordinate transport code ANISN and Vitamin-C nuclear data file. The results have been used to study the question of establishment of equilibrium and of an associated fast neutron diffusion length in iron. The authors find that true equilibrium conditions are not established even inside a 3-m-radius iron sphere. However, from the study of spatial decay of total flux, one can obtain the value of the fast neutron diffusion length in iron, which in the present case is found to be 24.4 cm

Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo

OpenAIRE

Soe-Lin, Shan; Apte, Sameer S.; Andriopoulos, Billy; Andrews, Marc C.; Schranzhofer, Matthias; Kahawita, Tanya; Garcia-Santos, Daniel; Ponka, Prem

2009-01-01

Natural resistance-associated macrophage protein 1 (Nramp1) is a divalent metal transporter expressed exclusively in phagocytic cells. We hypothesized that macrophage Nramp1 may participate in the recycling of iron acquired from phagocytosed senescent erythrocytes. To evaluate the role of Nramp1 in vivo, the iron parameters of WT and KO mice were analyzed after acute and chronic induction of hemolytic anemia. We found that untreated KO mice exhibited greater serum transferrin saturation and s...

Iron from Zealandic bog iron ore -

DEFF Research Database (Denmark)

Lyngstrøm, Henriette Syrach

2011-01-01

og geologiske materiale, metallurgiske analyser og eksperimentel arkæologiske forsøg - konturerne af en jernproduktion med udgangspunkt i den sjællandske myremalm. The frequent application by archaeologists of Werner Christensen’s distribution map for the occurrence of bog iron ore in Denmark (1966...... are sketched of iron production based on bog iron ore from Zealand....

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

Science.gov (United States)

Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

The Properties Of And Transport Phenomena In Oxide Films On Iron, Nickel, Chromium And Their Alloys In Aqueous Environments

International Nuclear Information System (INIS)

Saario, T.; Laitinen, T.; Maekelae, K.; Bojinov, M.; Betova, I.

1998-07-01

The construction materials used in coolant systems in nuclear power plants become covered with oxide films as a result of exposure to the aqueous environment. The susceptibility of the materials to different forms of corrosion, as well as the extent of the incorporation of radioactive species on the surfaces of the primary circuit, are greatly influenced by the physical and chemical properties of these oxide films. The composition and characteristics of the oxide films in turn depend on the applied water chemistry. This work was undertaken in order to collect and evaluate the present views on the structure and behaviour of oxide films formed on iron- and nickel-based materials in aqueous environments. This survey should serve to recognise the areas in which more understanding and research effort is needed. The review begins with a discussion on the bulk oxides of iron, nickel and chromium, as well as their mixed oxides. In addition to bulk oxides, the structure and properties of oxide films forming on pure iron, nickel and chromium and on iron- and nickel-based engineering alloys are considered. General approaches to model the structure and growth of oxide films on metals are discussed in detail. The specific features of the oxide structures, properties and growth at high temperatures are presented with special focus on the relevance of existing models. Finally, the role of oxide films in localised corrosion, oxide breakdown, pitting, stress corrosion cracking and related phenomena is considered. The films formed on the surfaces of iron- and nickel-based alloys in high-temperature aqueous environments generally comprise two layers, i.e. the so-called duplex structure. The inner part is normally enriched in chromium and has a more dense structure, while the outer part is enriched in iron and has a cracked or porous structure. The information collected clearly indicates the effect of the chemical environment on the properties of oxide films growing on metal surfaces

An Integrated Response of Trichodesmium erythraeum IMS101 Growth and Photo-Physiology to Iron, CO2, and Light Intensity.

Science.gov (United States)

Boatman, Tobias G; Oxborough, Kevin; Gledhill, Martha; Lawson, Tracy; Geider, Richard J

2018-01-01

We have assessed how varying CO 2 (180, 380, and 720 μatm) and growth light intensity (40 and 400 μmol photons m -2 s -1 ) affected Trichodesmium erythraeum IMS101 growth and photophysiology over free iron (Fe') concentrations between 20 and 9,600 pM. We found significant iron dependencies of growth rate and the initial slope and maximal relative PSII electron transport rates (rP m ). Under iron-limiting concentrations, high-light increased growth rates and rP m ; possibly indicating a lower allocation of resources to iron-containing photosynthetic proteins. Higher CO 2 increased growth rates across all iron concentrations, enabled growth to occur at lower Fe' concentrations, increased rP m and lowered the iron half saturation constants for growth (K m ). We attribute these CO 2 responses to the operation of the CCM and the ATP spent/saved for CO 2 uptake and transport at low and high CO 2 , respectively. It seems reasonable to conclude that T. erythraeum IMS101 can exhibit a high degree of phenotypic plasticity in response to CO 2 , light intensity and iron-limitation. These results are important given predictions of increased dissolved CO 2 and water column stratification (i.e., higher light exposures) over the coming decades.

An Integrated Response of Trichodesmium erythraeum IMS101 Growth and Photo-Physiology to Iron, CO2, and Light Intensity

Directory of Open Access Journals (Sweden)

Tobias G. Boatman

2018-04-01

Full Text Available We have assessed how varying CO2 (180, 380, and 720 μatm and growth light intensity (40 and 400 μmol photons m−2 s−1 affected Trichodesmium erythraeum IMS101 growth and photophysiology over free iron (Fe′ concentrations between 20 and 9,600 pM. We found significant iron dependencies of growth rate and the initial slope and maximal relative PSII electron transport rates (rPm. Under iron-limiting concentrations, high-light increased growth rates and rPm; possibly indicating a lower allocation of resources to iron-containing photosynthetic proteins. Higher CO2 increased growth rates across all iron concentrations, enabled growth to occur at lower Fe′ concentrations, increased rPm and lowered the iron half saturation constants for growth (Km. We attribute these CO2 responses to the operation of the CCM and the ATP spent/saved for CO2 uptake and transport at low and high CO2, respectively. It seems reasonable to conclude that T. erythraeum IMS101 can exhibit a high degree of phenotypic plasticity in response to CO2, light intensity and iron-limitation. These results are important given predictions of increased dissolved CO2 and water column stratification (i.e., higher light exposures over the coming decades.

Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease

DEFF Research Database (Denmark)

Wikström, Björn; Bhandari, Sunil; Barany, Peter

2011-01-01

Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency...... anemia....

The Effect Of Local Coal And Smelting Sponge Iron On Iron Content Of Pig Iron

Science.gov (United States)

Oediyani, Soesaptri; Juwita Sari, Pramita; Hadi P, Djoko

2018-03-01

The new regulation on mineral resources was announced by Ministry of Energy and Mineral resources (ESDM) of Indonesia at 2014 which it called Permen ESDM No 1/2014. Therefore, this research was conducted to add the value of local iron ores by using smelting technology. The objective of the research is to produce pig iron that meet the requirement of the new regulation of mineral resources such as 90% Fe. First, iron ores and coal mixed together with lime as a flux, then smelted in a Electric Arc Furnace at 1800°C. The process variables are (1; 1.25; 1.5; 1.75; 2.0) and the composition of coal (0.8%, 1.6%, 3.0%). The type of coal that used in this research was bituminous coal from Kalimantan and also the iron ores from Kalimantan. The products of the smelting technology are Pig iron and slag. Both pig iron and slag then analyzed by SEM-EDS to measure the iron content. The result shows that the maximum iron content on pig iron is about 95.04% meanwhile the minimum iron content on slag is about 3.66%. This result achieved at 1.6% coal and 2.0.

Iron biomineralization by anaerobic neutrophilic iron-oxidizing bacteria

DEFF Research Database (Denmark)

Miot, Jennyfer; Benzerara, Karim; Morin, Guillaume

2009-01-01

Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate-dependent ......Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate...... precipitation in the periplasm (in a few tens of minutes), followed by the formation of surface-bound globules. Moreover, we frequently observed an asymmetric mineral thickening at the cell poles. In parallel, the evolution of iron oxidation was quantified by STXM: iron both contained in the bacteria...... and in the extracellular precipitates reached complete oxidation within 6 days. While a progressive oxidation of Fe in the bacteria and in the medium could be observed, spatial redox (oxido-reduction state) heterogeneities were detected at the cell poles and in the extracellular precipitates after 1 day. All...

Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents.

Science.gov (United States)

Miller, Marvin J; Zhu, Helen; Xu, Yanping; Wu, Chunrui; Walz, Andrew J; Vergne, Anne; Roosenberg, John M; Moraski, Garrett; Minnick, Albert A; McKee-Dolence, Julia; Hu, Jingdan; Fennell, Kelley; Kurt Dolence, E; Dong, Li; Franzblau, Scott; Malouin, Francois; Möllmann, Ute

2009-02-01

Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the "microbial war", extensive interdisciplinary research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase) and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics) and induction of iron limitation/starvation (Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of novel potent and selective anticancer agents are also described.

46 CFR 56.60-10 - Cast iron and malleable iron.

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Cast iron and malleable iron. 56.60-10 Section 56.60-10... APPURTENANCES Materials § 56.60-10 Cast iron and malleable iron. (a) The low ductility of cast iron and malleable iron should be recognized and the use of these metals where shock loading may occur should be...

Effects of an Acute Exercise Bout on Serum Hepcidin Levels

Directory of Open Access Journals (Sweden)

Raúl Domínguez

2018-02-01

Full Text Available Iron deficiency is a frequent and multifactorial disorder in the career of athletes, particularly in females. Exercise-induced disturbances in iron homeostasis produce deleterious effects on performance and adaptation to training; thus, the identification of strategies that restore or maintain iron homeostasis in athletes is required. Hepcidin is a liver-derived hormone that degrades the ferroportin transport channel, thus reducing the ability of macrophages to recycle damaged iron, and decreasing iron availability. Although it has been suggested that the circulating fraction of hepcidin increases during early post-exercise recovery (~3 h, it remains unknown how an acute exercise bout may modify the circulating expression of hepcidin. Therefore, the current review aims to determine the post-exercise expression of serum hepcidin in response to a single session of exercise. The review was carried out in the Dialnet, Elsevier, Medline, Pubmed, Scielo and SPORTDiscus databases, using hepcidin (and “exercise” or “sport” or “physical activity” as a strategy of search. A total of 19 articles were included in the review after the application of the inclusion/exclusion criteria. This search found that a single session of endurance exercise (intervallic or continuous at moderate or vigorous intensity (60–90% VO2peak stimulates an increase in the circulating levels of hepcidin between 0 h and 6 h after the end of the exercise bout, peaking at ~3 h post-exercise. The magnitude of the response of hepcidin to exercise seems to be dependent on the pre-exercise status of iron (ferritin and inflammation (IL-6. Moreover, oxygen disturbances and the activation of a hypoxia-induced factor during or after exercise may stimulate a reduction of hepcidin expression. Meanwhile, cranberry flavonoids supplementation promotes an anti-oxidant effect that may facilitate the post-exercise expression of hepcidin. Further studies are required to explore the effect

Metal-metal interaction mediates the iron induction of Drosophila MtnB

International Nuclear Information System (INIS)

Qiang, Wenjia; Huang, Yunpeng; Wan, Zhihui; Zhou, Bing

2017-01-01

Metallothionein (MT) protein families are a class of small and universal proteins rich in cysteine residues. They are synthesized in response to heavy metal stresses to sequester the toxic ions by metal-thiolate bridges. Five MT family members, namely MtnA, MtnB, MtnC, MtnD and MtnE, have been discovered and identified in Drosophila. These five isoforms of MTs are regulated by metal responsive transcription factor dMTF-1 and play differentiated but overlapping roles in detoxification of metal ions. Previous researches have shown that Drosophila MtnB responds to copper (Cu), cadmium (Cd) and zinc (Zn). Interestingly in this study we found that Drosophila MtnB expression also responds to elevated iron levels in the diet. Further investigations revealed that MtnB plays limited roles in iron detoxification, and the direct binding of MtnB to ferrous iron in vitro is also weak. The induction of MtnB by iron turns out to be mediated by iron interference of other metals, because EDTA at even a partial concentration of that of iron can suppress this induction. Indeed, in the presence of iron, zinc homeostasis is altered, as reflected by expression changes of zinc transporters dZIP1 and dZnT1. Thus, iron-mediated MtnB induction appears resulting from interrupted homeostasis of other metals such as zinc, which in turns induced MtnB expression. Metal-metal interaction may more widely exist than we expected. - Highlights: • Metallothionein B expression is regulated by iron in Drosophila melanogaster. • MtnB has limited physiological roles in iron detoxification. • Binding affinity of MtnB to iron is weak in vitro. • Induction of Drosophila MtnB by iron is mediated indirectly through metal-metal interaction.

Quantification of body iron and iron absorption in the REDS-II Donor Iron Status Evaluation (RISE) study.

Science.gov (United States)

Kiss, Joseph E; Birch, Rebecca J; Steele, Whitney R; Wright, David J; Cable, Ritchard G

2017-07-01

Repeated blood donation alters the iron balance of blood donors. We quantified these effects by analyzing changes in body iron as well as calculating iron absorbed per day for donors enrolled in a prospective study. For 1308 donors who completed a final study visit, we calculated total body iron at the enrollment and final visits and the change in total body iron over the course of the study. Taking into account iron lost from blood donations during the study and obligate losses, we also calculated the average amount of iron absorbed per day. First-time/reactivated donors at enrollment had iron stores comparable to previous general population estimates. Repeat donors had greater donation intensity and greater mean iron losses than first-time/reactivated donors, yet they had little change in total body iron over the study period, whereas first-time/reactivated donors had an average 35% drop. There was higher estimated iron absorption in the repeat donors (men: 4.49 mg/day [95% confidence interval [CI], 4.41-4.58 mg/day]; women: 3.75 mg/day [95% CI, 3.67-3.84 mg/day]) compared with estimated iron absorption in first-time/reactivated donors (men: 2.89 mg/day [95% CI, 2.75-3.04 mg/day]; women: 2.76 mg/day [95% CI, 2.64-2.87 mg/day]). The threshold for negative estimated iron stores (below "0" mg/kg stores) was correlated with the development of anemia at a plasma ferritin value of 10 ng/mL. These analyses provide quantitative data on changes in estimated total body iron for a broad spectrum of blood donors. In contrast to using ferritin alone, this model allows assessment of the iron content of red blood cells and the degree of both iron surplus and depletion over time. © 2017 AABB.

Iron-Deficiency Anemia

Medline Plus

Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

[Partitioning of taxifolin-iron ions complexes in octanol-water system].

Science.gov (United States)

Shatalin, Iu V; Shubina, V S

2014-01-01

The composition of taxifolin-iron ions complexes in an octanol-water biphasic system was studied using the method of absorption spectrophotometry. It was found that at pH 5.0 in an aqueous biphasic system the complex of [Tf2 x Fe x (OH)k(H2O)8-k] is present, but at pH 7.0 and 9.0 the complexes of [Tf2 x Fe x (OH)k(H2O)2-k] and [Tf x Fe x OH)k(H2O)4-k] are predominantly observed. The formation of a stable [Tf3 x Fe] complex occurred in octanol phase. The charged iron ion of this complex is surrounded by taxifolin molecules, which shield the iron ion from lipophilic solvent. During transition from water to octanol phase the changes of the composition of complexes are accompanied by reciprocal changes in portion of taxifolin and iron ions in these phases. It was shown that the portion of taxifolin in aqueous solution in the presence of iron ions is increased at high pH values, and the portion of iron ions is minimal at pH 7.0. In addition, the parameters of solubility limits of taxifolin-iron ions complexes in an aqueous solution were determined. The data obtained gain a better understanding of the role of complexation of polyphenol with metal of variable valency in passive transport of flavonoids and metal ions across lipid membranes.

Is there a strategy I iron uptake mechanism in maize?

Science.gov (United States)

Li, Suzhen; Zhou, Xiaojin; Chen, Jingtang; Chen, Rumei

2018-04-03

Iron is a metal micronutrient that is essential for plant growth and development. Graminaceous and nongraminaceous plants have evolved different mechanisms to mediate Fe uptake. Generally, strategy I is used by nongraminaceous plants like Arabidopsis, while graminaceous plants, such as rice, barley, and maize, are considered to use strategy II Fe uptake. Upon the functional characterization of OsIRT1 and OsIRT2 in rice, it was suggested that rice, as an exceptional graminaceous plant, utilizes both strategy I and strategy II Fe uptake systems. Similarly, ZmIRT1 and ZmZIP3 were identified as functional zinc and iron transporters in the maize genome, along with the determination of several genes encoding Zn and Fe transporters, raising the possibility that strategy I Fe uptake also occurs in maize. This mini-review integrates previous reports and recent evidence to obtain a better understanding of the mechanisms of Fe uptake in maize.

"Conjugate channeling" effect in dislocation core diffusion: carbon transport in dislocated BCC iron.

Science.gov (United States)

Ishii, Akio; Li, Ju; Ogata, Shigenobu

2013-01-01

Dislocation pipe diffusion seems to be a well-established phenomenon. Here we demonstrate an unexpected effect, that the migration of interstitials such as carbon in iron may be accelerated not in the dislocation line direction ξ, but in a conjugate diffusion direction. This accelerated random walk arises from a simple crystallographic channeling effect. c is a function of the Burgers vector b, but not ξ, thus a dislocation loop possesses the same everywhere. Using molecular dynamics and accelerated dynamics simulations, we further show that such dislocation-core-coupled carbon diffusion in iron has temperature-dependent activation enthalpy like a fragile glass. The 71° mixed dislocation is the only case in which we see straightforward pipe diffusion that does not depend on dislocation mobility.

Transport of poly(acrylic acid) coated 2-line ferrihydrite nanoparticles in saturated aquifer sediments for environmental remediation

Science.gov (United States)

Xiang, Aishuang; Zhou, Sheng; Koel, Bruce E.; Jaffé, Peter R.

2014-04-01

Groundwater remediation using iron oxide and zero-valent iron nanoparticles (NPs) can be effective, but is limited in many applications due to the NP strong retention in groundwater-saturated porous media after injection, the passivation of the porous surface, and the high cost of nanomaterials versus macro scale iron. In this study, we investigated transport of bare and polymer-coated 2-line ferrihydrite NPs (30-300 nm) in saturated aquifer sediments. The influence of poly(acrylic acid) (PAA) polymer coatings was studied on the colloidal stability and transport in sediments packed column tests simulating groundwater flow in saturated sediments. In addition, the influence of calcium cations was investigated by transport measurements using sediments with calcium concentrations in the aqueous phase ranging from 0.5 (typical for most sediments) to 2 mM. Measurements were also made of zeta potential, hydrodynamic diameter, polymer adsorption and desorption properties, and bio-availability of PAA-coated NPs. We found that NP transport through the saturated aquifer sediments was improved by PAA coating and that the transport properties could be tuned by adjusting the polymer concentration. We further discovered that PAA coatings enhanced NP transport, compared to bare NPs, in all calcium-containing experiments tested, however, the presence of calcium always exhibited a negative effect on NP transport. In tests of bioavailability, the iron reduction rate of the coated and bare NPs by Geobacter sulfurreducens was the same, which shows that the PAA coating does not significantly reduce NP Fe(III) bioavailability. Our results demonstrate that much improved transport of iron oxide NP can be achieved in saturated aquifer sediments by introducing negatively charged polyelectrolytes and optimizing polymer concentrations, and furthermore, these coated NPs retain their bioavailability that is needed for applications in bio-environmental remediation.

Bioavailable iron in the Southern Ocean: the significance of the iceberg conveyor belt.

Science.gov (United States)

Raiswell, Rob; Benning, Liane G; Tranter, Martyn; Tulaczyk, Slawek

2008-05-30

Productivity in the Southern Oceans is iron-limited, and the supply of iron dissolved from aeolian dust is believed to be the main source from outside the marine reservoir. Glacial sediment sources of iron have rarely been considered, as the iron has been assumed to be inert and non-bioavailable. This study demonstrates the presence of potentially bioavailable Fe as ferrihydrite and goethite in nanoparticulate clusters, in sediments collected from icebergs in the Southern Ocean and glaciers on the Antarctic landmass. Nanoparticles in ice can be transported by icebergs away from coastal regions in the Southern Ocean, enabling melting to release bioavailable Fe to the open ocean. The abundance of nanoparticulate iron has been measured by an ascorbate extraction. This data indicates that the fluxes of bioavailable iron supplied to the Southern Ocean from aeolian dust (0.01-0.13 Tg yr(-1)) and icebergs (0.06-0.12 Tg yr(-1)) are comparable. Increases in iceberg production thus have the capacity to increase productivity and this newly identified negative feedback may help to mitigate fossil fuel emissions.

Detailed non-LTE calculations of the iron emission from NGC 1068