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Sample records for iron metabolism limits

  1. METABOLISM OF IRON STORES

    PubMed Central

    SAITO, HIROSHI

    2014-01-01

    ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since the pioneering research by Shoden in 1953. However, we recently developed a new method for determining ferritin iron and hemosiderin iron by computer-assisted serum ferritin kinetics. Serum ferritin increase or decrease curves were measured in patients with normal storage iron levels (chronic hepatitis C and iron deficiency anemia treated by intravenous iron injection), and iron overload (hereditary hemochromatosis and transfusion dependent anemia). We thereby confirmed the existence of two iron pathways where iron flows followed the numbered order (1) labile iron, (2) ferritin and (3) hemosiderin in iron deposition and mobilization among many previously proposed but mostly unproven routes. We also demonstrated the increasing and decreasing phases of ferritin iron and hemosiderin iron in iron deposition and mobilization. The author first demonstrated here the change in proportion between pre-existing ferritin iron and new ferritin iron synthesized by removing iron from hemosiderin in the course of iron removal. In addition, the author disclosed the cause of underestimation of storage iron turnover rate which had been reported by previous investigators in estimating storage iron turnover rate of normal subjects. PMID:25741033

  2. Hepatic iron metabolism.

    PubMed

    Anderson, Gregory J; Frazer, David M

    2005-11-01

    The liver performs three main functions in iron homeostasis. It is the major site of iron storage, it regulates iron traffic into and around the body through its production of the peptide hepcidin, and it is the site of synthesis of major proteins of iron metabolism such as transferrin and ceruloplasmin. Most of the iron that enters the liver is derived from plasma transferrin under normal circumstances, and transferrin receptors 1 and 2 play important roles in this process. In pathological situations, non-transferrin-bound iron, ferritin, and hemoglobin/haptoglobin and heme/hemopexin complexes assume greater importance in iron delivery to the organ. Iron is stored in the liver as ferritin and, with heavy iron loading, as hemosiderin. The liver can divest itself of iron through the plasma membrane iron exporter ferroportin 1, a process that also requires ceruloplasmin. Hepcidin can regulate this iron release through its interaction with ferroportin. PMID:16315136

  3. Knockdown of proteins involved in iron metabolism limits tick reproduction and development

    PubMed Central

    Hajdusek, Ondrej; Sojka, Daniel; Kopacek, Petr; Buresova, Veronika; Franta, Zdenek; Sauman, Ivo; Winzerling, Joy; Grubhoffer, Libor

    2009-01-01

    Ticks are among the most important vectors of a wide range of human and animal diseases. During blood feeding, ticks are exposed to an enormous amount of free iron that must be appropriately used and detoxified. However, the mechanism of iron metabolism in ticks is poorly understood. Here, we show that ticks possess a complex system that efficiently utilizes, stores and transports non-heme iron within the tick body. We have characterized a new secreted ferritin (FER2) and an iron regulatory protein (IRP1) from the sheep tick, Ixodes ricinus, and have demonstrated their relationship to a previously described tick intracellular ferritin (FER1). By using RNA interference-mediated gene silencing in the tick, we show that synthesis of FER1, but not of FER2, is subject to IRP1-mediated translational control. Further, we find that depletion of FER2 from the tick plasma leads to a loss of FER1 expression in the salivary glands and ovaries that normally follows blood ingestion. We therefore suggest that secreted FER2 functions as the primary transporter of non-heme iron between the tick gut and the peripheral tissues. Silencing of the fer1, fer2, and irp1 genes by RNAi has an adverse impact on hatching rate and decreases postbloodmeal weight in tick females. Importantly, knockdown of fer2 dramatically impairs the ability of ticks to feed, thus making FER2 a promising candidate for development of an efficient anti-tick vaccine. PMID:19171899

  4. Physiology of Iron Metabolism

    PubMed Central

    Waldvogel-Abramowski, Sophie; Waeber, Gérard; Gassner, Christoph; Buser, Andreas; Frey, Beat M.; Favrat, Bernard; Tissot, Jean-Daniel

    2014-01-01

    Summary A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. ‘Ironomics’ certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism. PMID:25053935

  5. Cellular iron metabolism in prognosis and therapy of breast cancer.

    PubMed

    Torti, Suzy V; Torti, Frank M

    2013-01-01

    Despite many recent advances, breast cancer remains a clinical challenge. Current issues include improving prognostic evaluation and increasing therapeutic options for women whose tumors are refractory to current frontline therapies. Iron metabolism is frequently disrupted in breast cancer, and may offer an opportunity to address these challenges. Iron enhances breast tumor initiation, growth and metastases. Iron may contribute to breast tumor initiation by promoting redox cycling of estrogen metabolites. Up-regulation of iron import and down-regulation of iron export may enable breast cancer cells to acquire and retain excess iron. Alterations in iron metabolism in macrophages and other cells of the tumor microenvironment may also foster breast tumor growth. Expression of iron metabolic genes in breast tumors is predictive of breast cancer prognosis. Iron chelators and other strategies designed to limit iron may have therapeutic value in breast cancer. The dependence of breast cancer on iron presents rich opportunities for improved prognostic evaluation and therapeutic intervention. PMID:23879588

  6. Iron metabolism in mammalian cells.

    PubMed

    Walker, B L; Tiong, J W; Jefferies, W A

    2001-01-01

    Most living things require iron to exist. Iron has many functions within cells but is rarely found unbound because of its propensity to catalyze the formation of toxic free radicals. Thus the regulation of iron requirements by cells and the acquisition and uptake of iron into tissues in multicellular organisms is tightly regulated. In humans, understanding iron transport and utility has recently been advanced by a "great conjunction" of molecular genetics in simple organisms, identifying genes involved in genetic diseases of metal metabolism and by the application of traditional cell physiology approaches. We are now able to approach a rudimentary understanding of the "iron cycle" within mammals. In the future, this information will be applied toward modulating the outcome of therapies designed to overcome diseases involving metals. PMID:11597005

  7. Iron metabolism: current facts and future directions

    PubMed Central

    Tandara, Leida; Salamunic, Ilza

    2012-01-01

    Iron metabolism has been intensively examined over the last decade and there are many new players in this field which are worth to be introduced. Since its discovery many studies confirmed role of liver hormone hepcidin as key regulator of iron metabolism and pointed out liver as the central organ of system iron homeostasis. Liver cells receive multiple signals related to iron balance and respond by transcriptional regulation of hepcidin expression. This liver hormone is negative regulator of iron metabolism that represses iron efflux from macrophages, hepatocytes and enterocytes by its binding to iron export protein ferroportin. Ferroportin degradation leads to cellular iron retention and decreased iron availability. At level of a cell IRE/IRP (iron responsive elements/iron responsive proteins) system allows tight regulation of iron assimilation that prevents an excess of free intracellular iron which could lead to oxidative stress and damage of DNA, proteins and lipid membranes by ROS (reactive oxygen species). At the same time IRE/IRP system provides sufficient iron in order to meet the metabolic needs. Recently a significant progress in understanding of iron metabolism has been made and new molecular participants have been characterized. Article gives an overview of the current understanding of iron metabolism: absorption, distribution, cellular uptake, release, and storage. We also discuss mechanisms underlying systemic and cellular iron regulation with emphasis on central regulatory hormone hepcidin. PMID:23092063

  8. Mechanisms of iron metabolism in Caenorhabditis elegans

    PubMed Central

    Anderson, Cole P.; Leibold, Elizabeth A.

    2014-01-01

    Iron is involved in many biological processes essential for sustaining life. In excess, iron is toxic due to its ability to catalyze the formation of free radicals that damage macromolecules. Organisms have developed specialized mechanisms to tightly regulate iron uptake, storage and efflux. Over the past decades, vertebrate model organisms have led to the identification of key genes and pathways that regulate systemic and cellular iron metabolism. This review provides an overview of iron metabolism in the roundworm Caenorhabditis elegans and highlights recent studies on the role of hypoxia and insulin signaling in the regulation of iron metabolism. Given that iron, hypoxia and insulin signaling pathways are evolutionarily conserved, C. elegans provides a genetic model organism that promises to provide new insights into mechanisms regulating mammalian iron metabolism. PMID:24904417

  9. Crosstalk between Iron Metabolism and Erythropoiesis

    PubMed Central

    Li, Huihui; Ginzburg, Yelena Z.

    2010-01-01

    Iron metabolism and erythropoiesis are inextricably linked. The majority of iron extracted from circulation daily is used for hemoglobin synthesis. In the last 15 years, major advances have been made in understanding the pathways regulating iron metabolism. Hepcidin is a key regulator of iron absorption and recycling and is itself regulated by erythropoiesis. While several viable candidates have been proposed, elucidating the “erythroid regulator” of hepcidin continues to generate significant experimental activity in the field. Although the mechanism responsible for sensing iron demand for erythropoiesis is still incompletely understood, evaluating diseases in which disordered erythropoiesis and/or iron metabolism are showcased has resulted in a more robust appreciation of potential candidates coordinated erythroid iron demand with regulators of iron supply. We present data drawn from four different conditions—iron deficiency, congenital hypotransferrinemia, beta-thalassemia, and hereditary hemochromatosis—both in human and non-human models of disease, together suggesting that erythroid iron demand exerts a stronger influence on circulating iron supply than systemic iron stores. Greater understanding of the interplay between the key factors involved in the regulation of iron metabolism and erythropoiesis will help develop more effective therapies for disorders of iron overload, iron deficiency, and hemoglobin synthesis. PMID:20631898

  10. A Systems Biology Approach to Iron Metabolism

    PubMed Central

    Chifman, J.; Laubenbacher, R.; Torti, S.V.

    2015-01-01

    Iron is critical to the survival of almost all living organisms. However, inappropriately low or high levels of iron are detrimental and contribute to a wide range of diseases. Recent advances in the study of iron metabolism have revealed multiple intricate pathways that are essential to the maintenance of iron homeostasis. Further, iron regulation involves processes at several scales, ranging from the subcellular to the organismal. This complexity makes a systems biology approach crucial, with its enabling technology of computational models based on a mathematical description of regulatory systems. Systems biology may represent a new strategy for understanding imbalances in iron metabolism and their underlying causes. PMID:25480643

  11. In vivo iron metabolism by IRMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Iron isotopes are used in both biological and geological investigations. Three low-abundance stable isotopes are available for human studies. They have been widely used to study iron metabolism. They have provided valuable insights into iron deficiency, one of the most common micronutrient deficienc...

  12. Mammalian iron metabolism and its control by iron regulatory proteins☆

    PubMed Central

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

    2013-01-01

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

  13. Iron utilization and metabolism in plants.

    PubMed

    Briat, Jean-François; Curie, Catherine; Gaymard, Frédéric

    2007-06-01

    The solubilization and long-distance allocation of iron between organs and tissues, as well as its subcellular compartmentalization and remobilization, involve various chelation and oxidation/reduction steps, transport activities and association with soluble proteins that store and buffer this metal. Maintaining iron homeostasis is an important determinant in building prosthetic groups such as heme and Fe-S clusters, and in assembling them into apoproteins, which are major components of plant metabolism. Such processes require complex protein machineries located in mitochondria and plastids. An essential role for iron metabolism and utilization in plant productivity is evidenced by the strong iron requirement for proper photosynthetic reactions. PMID:17434791

  14. [Phosphate metabolism and iron deficiency].

    PubMed

    Yokoyama, Keitaro

    2016-02-01

    Autosomal dominant hypophosphatemic rickets(ADHR)is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage. Fibroblast growth factor 23(FGF23)is a hormone that inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D biosynthesis. Low iron status plays a role in the pathophysiology of ADHR. Iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. It was reported that FGF23 elevation in patients with CKD, who are often iron deficient. In patients with nondialysis-dependent CKD, treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and FGF23. PMID:26813504

  15. Diversity and Evolutionary History of Iron Metabolism Genes in Diatoms

    PubMed Central

    Groussman, Ryan D.; Parker, Micaela S.; Armbrust, E. Virginia

    2015-01-01

    Ferroproteins arose early in Earth’s history, prior to the emergence of oxygenic photosynthesis and the subsequent reduction of bioavailable iron. Today, iron availability limits primary productivity in about 30% of the world’s oceans. Diatoms, responsible for nearly half of oceanic primary production, have evolved molecular strategies for coping with variable iron concentrations. Our understanding of the evolutionary breadth of these strategies has been restricted by the limited number of species for which molecular sequence data is available. To uncover the diversity of strategies marine diatoms employ to meet cellular iron demands, we analyzed 367 newly released marine microbial eukaryotic transcriptomes, which include 47 diatom species. We focused on genes encoding proteins previously identified as having a role in iron management: iron uptake (high-affinity ferric reductase, multi-copper oxidase, and Fe(III) permease); iron storage (ferritin); iron-induced protein substitutions (flavodoxin/ferredoxin, and plastocyanin/cytochrome c6) and defense against reactive oxygen species (superoxide dismutases). Homologs encoding the high-affinity iron uptake system components were detected across the four diatom Classes suggesting an ancient origin for this pathway. Ferritin transcripts were also detected in all Classes, revealing a more widespread utilization of ferritin throughout diatoms than previously recognized. Flavodoxin and plastocyanin transcripts indicate possible alternative redox metal strategies. Predicted localization signals for ferredoxin identify multiple examples of gene transfer from the plastid to the nuclear genome. Transcripts encoding four superoxide dismutase metalloforms were detected, including a putative nickel-coordinating isozyme. Taken together, our results suggest that the majority of iron metabolism genes in diatoms appear to be vertically inherited with functional diversity achieved via possible neofunctionalization of paralogs. This

  16. [Iron metabolism: pathophysiology and biomarkers in elderly population].

    PubMed

    Gavazzi, Gaëtan

    2014-06-01

    Iron deficiency is frequent in elderly population and is responsable for numerous clinical situations. Because of the frequent association of inflammatory diseases, chronic diseases associated with iron loss, diagnosis of iron deficiency is often difficult in elderly population. For the last ten years, new biomarkers of iron physiology lead to better understand physiology and pathophysiology of iron metabolism particularly in iron deficiency. This overview aims to show modifications of iron metabolism with ageing, pathophysiological mecanisms associated with iron deficiency and give a stratification of the use of biomarkers as diagnostic tools differentiating absolute deficiency or functional deficeincy. PMID:25031216

  17. Effects of Pregnancy and Lactation on Iron Metabolism in Rats

    PubMed Central

    Gao, Guofen; Liu, Shang-Yuan; Wang, Hui-Jie; Zhang, Tian-Wei; Yu, Peng; Duan, Xiang-Lin; Zhao, Shu-E; Chang, Yan-Zhong

    2015-01-01

    In female, inadequate iron supply is a highly prevalent problem that often leads to iron-deficiency anemia. This study aimed to understand the effects of pregnancy and lactation on iron metabolism. Rats with different days of gestation and lactation were used to determine the variations in iron stores and serum iron level and the changes in expression of iron metabolism-related proteins, including ferritin, ferroportin 1 (FPN1), ceruloplasmin (Cp), divalent metal transporter 1 (DMT1), transferrin receptor 1 (TfR1), and the major iron-regulatory molecule—hepcidin. We found that iron stores decline dramatically at late-pregnancy period, and the low iron store status persists throughout the lactation period. The significantly increased FPN1 level in small intestine facilitates digestive iron absorption, which maintains the serum iron concentration at a near-normal level to meet the increase of iron requirements. Moreover, a significant decrease of hepcidin expression is observed during late-pregnancy and early-lactation stages, suggesting the important regulatory role that hepcidin plays in iron metabolism during pregnancy and lactation. These results are fundamental to the understanding of iron homeostasis during pregnancy and lactation and may provide experimental bases for future studies to identify key molecules expressed during these special periods that regulate the expression of hepcidin, to eventually improve the iron-deficiency status. PMID:26788496

  18. Physiological and Proteomic Analysis of Escherichia coli Iron-Limited Chemostat Growth

    PubMed Central

    Folsom, James Patrick; Parker, Albert E.

    2014-01-01

    Iron bioavailability is a major limiter of bacterial growth in mammalian host tissue and thus represents an important area of study. Escherichia coli K-12 metabolism was studied at four levels of iron limitation in chemostats using physiological and proteomic analyses. The data documented an E. coli acclimation gradient where progressively more severe iron scarcity resulted in a larger percentage of substrate carbon being directed into an overflow metabolism accompanied by a decrease in biomass yield on glucose. Acetate was the primary secreted organic by-product for moderate levels of iron limitation, but as stress increased, the metabolism shifted to secrete primarily lactate (∼70% of catabolized glucose carbon). Proteomic analysis reinforced the physiological data and quantified relative increases in glycolysis enzyme abundance and decreases in tricarboxylic acid (TCA) cycle enzyme abundance with increasing iron limitation stress. The combined data indicated that E. coli responds to limiting iron by investing the scarce resource in essential enzymes, at the cost of catabolic efficiency (i.e., downregulating high-ATP-yielding pathways containing enzymes with large iron requirements, like the TCA cycle). Acclimation to iron-limited growth was contrasted experimentally with acclimation to glucose-limited growth to identify both general and nutrient-specific acclimation strategies. While the iron-limited cultures maximized biomass yields on iron and increased expression of iron acquisition strategies, the glucose-limited cultures maximized biomass yields on glucose and increased expression of carbon acquisition strategies. This study quantified ecologically competitive acclimations to nutrient limitations, yielding knowledge essential for understanding medically relevant bacterial responses to host and to developing intervention strategies. PMID:24837288

  19. METABOLIC CAPACITY REGULATES IRON HOMEOSTATIS IN ENDOTHELIAL CELLS

    EPA Science Inventory

    The sensitivity of endothelial cells to oxidative stress and the high concentrations of iron in mitochondria led us to test the hypotheses that (1) changes in respiratory capacity alter iron homeostasis, and (2) lack of aerobic metabolism decreases labile iron stores and attenuat...

  20. Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism

    PubMed Central

    Horniblow, Richard D.; Dowle, Miriam; Iqbal, Tariq H.; Latunde-Dada, Gladys O.; Palmer, Richard E.

    2015-01-01

    Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease. PMID:26378798

  1. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease.

    PubMed

    Panwar, Bhupesh; Gutiérrez, Orlando M

    2016-07-01

    Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD. In addition, emerging evidence has suggested that iron homeostasis interacts with bone and mineral metabolism on multiple levels, opening up new avenues of investigation into the genesis of disordered iron metabolism in CKD. Building on recent advances in our understanding of normal iron physiology and abnormalities in iron homeostasis in CKD, this review characterizes how anemia related to disordered iron metabolism develops in the setting of CKD. In addition, this review explores our emerging recognition of the connections between iron homeostasis and mineral metabolism and their implications for the management of altered iron status and anemia of CKD. PMID:27475656

  2. Oral iron treatment has a positive effect on iron metabolism in elite soccer players.

    PubMed

    Villanueva, Jesús; Soria, Marisol; González-Haro, Carlos; Ezquerra, Laura; Nieto, José L; Escanero, Jesús F

    2011-09-01

    The purpose of this study was to assess the effects of oral iron supplementation on hematological and iron metabolism in elite soccer players. Thirty-five members of the Real Zaragoza SAD soccer team took part in this study: group A (GA, n = 24; Spanish Premier League) took an oral iron supplement of 80 mg day(-1) for 3 weeks, and group B (GB, n = 11; Spanish Third Division League) did not receive any supplementation. In GA, the parameters were measured before and after giving the iron supplements, while in GB, measurements were only made at the time of collecting the second set of data from GA. After supplementation, GA showed an increase in serum iron (SI) (P < 0.05), serum ferritin (Ftn) (P < 0.01), and transferrin saturation (Sat) (P < 0.01) with respect to the basal values. In addition, GA showed higher values of hematocrit (P < 0.01), mean corpuscular volume (P < 0.01), Ftn (P < 0.01), and Sat (P < 0.01) than GB. No significant differences were found in any other parameters. More specifically, a higher percentage of players had Ftn levels above upper limits in GA vs. GB (P < 0.05), and GB had a higher incidence of Ftn below lower limits with respect to subjects in GA (P < 0.01). Further, after treatment, 58.3% of GA had >800 mg of SI, while all players in GB presented levels below the lower limits. In conclusion, iron supplementation with 80 mg·day(-1) for 3 weeks, before the start of the soccer season, can be recommended for elite soccer players. PMID:20798998

  3. Recent Advances in Iron Metabolism: Relevance for Health, Exercise, and Performance.

    PubMed

    Buratti, Paolo; Gammella, Elena; Rybinska, Ilona; Cairo, Gaetano; Recalcati, Stefania

    2015-08-01

    Iron is necessary for physiological processes essential for athletic performance, such as oxygen transport, energy production, and cell division. However, an excess of "free" iron is toxic because it produces reactive hydroxyl radicals that damage biological molecules, thus leading to cell and tissue injury. Therefore, iron homeostasis is strictly regulated; and in recent years, there have been important advancements in our knowledge of the underlying processes. Hepcidin is the central regulator of systemic iron homeostasis and exerts its function by controlling the presence of the iron exporter ferroportin on the cell membrane. Hepcidin binding induces ferroportin degradation, thus leading to cellular iron retention and decreased levels of circulating iron. As iron is required for hemoglobin synthesis, the tight link between erythropoiesis and iron metabolism is particularly relevant to sports physiology. The iron needed for hemoglobin synthesis is ensured by inhibiting hepcidin to increase ferroportin activity and iron availability and hence to make certain that efficient blood oxygen transport occurs for aerobic exercise. However, hepcidin expression is also affected by exercise-associated conditions, such as iron deficiency, anemia or hypoxia, and, particularly, inflammation, which can play a role in the pathogenesis of sports anemia. Here, we review recent advances showing the relevance of iron for physical exercise and athletic performance. Low body iron levels can cause anemia and thus limit the delivery of oxygen to exercising muscle, but tissue iron deficiency may also affect performance by, for example, hampering muscle oxidative metabolism. Accordingly, a hemoglobin-independent effect of iron on exercise capacity has been demonstrated in animal models and humans. Here, we review recent advances showing the relevance of iron for physical exercise and athletic performance. PMID:25494391

  4. Molecular and Cellular Bases of Iron Metabolism in Humans.

    PubMed

    Milto, I V; Suhodolo, I V; Prokopieva, V D; Klimenteva, T K

    2016-06-01

    Iron is a microelement with the most completely studied biological functions. Its wide dissemination in nature and involvement in key metabolic pathways determine the great importance of this metal for uni- and multicellular organisms. The biological role of iron is characterized by its indispensability in cell respiration and various biochemical processes providing normal functioning of cells and organs of the human body. Iron also plays an important role in the generation of free radicals, which under different conditions can be useful or damaging to biomolecules and cells. In the literature, there are many reviews devoted to iron metabolism and its regulation in pro- and eukaryotes. Significant progress has been achieved recently in understanding molecular bases of iron metabolism. The purpose of this review is to systematize available data on mechanisms of iron assimilation, distribution, and elimination from the human body, as well as on its biological importance and on the major iron-containing proteins. The review summarizes recent ideas about iron metabolism. Special attention is paid to mechanisms of iron absorption in the small intestine and to interrelationships of cellular and extracellular pools of this metal in the human body. PMID:27301283

  5. Divergence of iron metabolism in wild Malaysian yeast.

    PubMed

    Lee, Hana N; Mostovoy, Yulia; Hsu, Tiffany Y; Chang, Amanda H; Brem, Rachel B

    2013-12-01

    Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics. PMID:24142925

  6. Size-fractionated iron distributions and iron-limitation processes in the subarctic NW Pacific

    NASA Astrophysics Data System (ADS)

    Nishioka, Jun; Takeda, Shigenobu; Kudo, Isao; Tsumune, Daisuke; Yoshimura, Takeshi; Kuma, Kenshi; Tsuda, Atsushi

    2003-07-01

    Comparison of vertical profiles of size-fractionated iron between the western and eastern subarctic North Pacific clearly showed higher labile particulate iron concentrations towards the west and this result strongly supports the higher iron supply in the western region. Additionally, the results of the SEEDS experiment, the first meso-scale iron enrichment experiment in the subarctic North Pacific, clearly showed that artificially enriched iron in the dissolved fraction (mainly in colloidal fraction) was rapidly transformed to suspended labile particulate iron during phytoplankton growth and was retained in the surface mixed layer. Probably, this same rapid transformation process occurs naturally after sporadic atmospheric iron supply and the labile particulate iron is retained in the western region. Furthermore, this transformation process reduces dissolved concentration of iron and its bioavailability. Therefore, the transformation process is important for understanding how phytoplankton became iron limited and the biogeochemical iron cycle in the western subarctic North Pacific.

  7. New developments and controversies in iron metabolism and iron chelation therapy

    PubMed Central

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-01-01

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients’ therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic

  8. New developments and controversies in iron metabolism and iron chelation therapy.

    PubMed

    Kontoghiorghe, Christina N; Kontoghiorghes, George J

    2016-03-26

    Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic

  9. Oxidative Stress and the Homeodynamics of Iron Metabolism

    PubMed Central

    Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

    Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress. PMID:25970586

  10. Limits to sustainable human metabolic rate.

    PubMed

    Westerterp, K R

    2001-09-01

    There is a limit to the performance of an organism set by energy intake and energy mobilization. Here, the focus is on humans with unlimited access to food and for whom physical activity can be limited by energy mobilization. The physical activity level (PAL) in the general population, calculated as doubly-labelled-water-assessed average daily metabolic rate as a multiple of basal metabolic rate, has an upper limit of 2.2-2.5. The upper limit of sustainable metabolic rate is approximately twice as high in endurance athletes, mainly because of long-term exercise training with simultaneous consumption of carbohydrate-rich food during exercise. Endurance athletes have an increased fat-free mass and can maintain energy balance at a PAL value of 4.0-5.0. High altitude limits exercise performance as a result of combined effects on nutrient supply and the capacity to process nutrients. Thus, trained subjects climbing Mount Everest reached PAL values of 2.0-2.7, well below the observed upper limit at sea level. PMID:11581332

  11. Growth of Aerobic Ripening Bacteria at the Cheese Surface Is Limited by the Availability of Iron

    PubMed Central

    Back, Alexandre; Irlinger, Françoise

    2012-01-01

    The microflora on the surface of smear-ripened cheeses is composed of various species of bacteria and yeasts that contribute to the production of the desired organoleptic properties. The objective of the present study was to show that iron availability is a limiting factor in the growth of typical aerobic ripening bacteria in cheese. For that purpose, we investigated the effect of iron or siderophore addition in model cheeses that were coinoculated with a yeast and a ripening bacterium. Both iron and the siderophore desferrioxamine B stimulated the growth of ripening bacteria belonging to the genera Arthrobacter, Corynebacterium, and Brevibacterium. The extent of stimulation was strain dependent, and generally, the effect of desferrioxamine B was greater than that of iron. Measurements of the expression of genes related to the metabolism of iron by Arthrobacter arilaitensis Re117 by real-time reverse transcription-PCR showed that these genes were transcribed during growth in cheese. The addition of desferrioxamine B increased the expression of two genes encoding iron-siderophore ABC transport binding proteins. The addition of iron decreased the expression of siderophore biosynthesis genes and of part of the genes encoding iron-siderophore ABC transport components. It was concluded that iron availability is a limiting factor in the growth of typical cheese surface bacteria. The selection of strains with efficient iron acquisition systems may be useful for the development of defined-strain surface cultures. Furthermore, the importance of iron metabolism in the microbial ecology of cheeses should be investigated since it may result in positive or negative microbial interactions. PMID:22367081

  12. Dissolved iron supply limits early growth of estuarine mangroves.

    PubMed

    Alongi, Daniel M

    2010-11-01

    Three mesocosm experiments were performed in an outdoor facility to quantify the responses of five mangrove species grown from seedling to sapling stage to increasing rates of dissolved iron supply. Stem extension and biomass of mangroves were measured in the first two experiments, and in the third experiment, rates of microbial iron reduction were measured in relation to stem extension of two mangrove species. In all experiments, mangrove growth was enhanced by increasing iron supply, although some species showed iron toxicity at the higher supply rates. In the first two experiments, stem extension rates of Rhizophora apiculata, Bruguiera gymnorrhiza, and Xylocarpus moluccensis best fit Gaussian curves with maximal growth at supply rates of 50-60 mmol Fe x m(-2) x d(-1), whereas growth of Avicennia marina and Ceriops tagal increased to the highest rate (100 mmol Fe x m(-2) x d(-1)) of iron supply. Changes in leaf chlorophyll concentrations and iron content of roots mirrored the growth responses. In the third experiment, rates of microbial iron reduction were greater with R. apiculata and A. marina than in controls without plants; for both species, there was a positive relationship between stem extension and iron reduction. The rates of iron reduction and rates of iron supplied to the plants were well within the range of interstitial iron concentrations and rates of iron reduction found in the natural mangrove soils from which the seedlings were obtained. The responses of these species show that mangroves growing from seedling to sapling stage have a strong nutritional requirement for iron, and that there is a close relationship between plant roots and the activities of iron-reducing bacteria. These results suggest that mangrove growth may be limited in some natural forests by the rate at which iron is solubilized by iron-reducing bacteria. Such biogeochemical conditions have significant implications for successful recruitment, establishment, and early growth of

  13. Iron uptake and metabolism in pseudomonads.

    PubMed

    Cornelis, Pierre

    2010-05-01

    Pseudomonads are ubiquitous Gram-negative gamma proteobacteria known for their extreme versatility and adaptability. Some are plant pathogens (Pseudomonas syringae) which have to survive on the surface of leaves while others can colonize the rhizosphere or survive in soil (Pseudomonas fluorescens, Pseudomonas putida), and one species, Pseudomonas entomophila, is an insect pathogen. The most investigated species, Pseudomonas aeruginosa, is known to be an opportunistic pathogen able to infect plants, nematodes, insects, and mammals, including humans. Like for other bacteria, iron is a key nutrient for pseudomonads. The fluorescent pseudomonads produce siderophores, the best known being the fluorescent high-affinity peptidic pyoverdines. Often diverse secondary siderophores of lower affinity are produced as well (pyochelin, pseudomonin, corrugatins and ornicorrugatins, yersiniabactin, and thioquinolobactin). Reflecting their large capacity of adaptation to changing environment and niche colonization, pseudomonads are able to obtain their iron from heme or from siderophores produced by other microorganisms (xenosiderophores) via the expression of outer membrane TonB-dependent receptors. As expected, iron uptake is exquisitely and hierarchically regulated in these bacteria. In this short review, the diversity of siderophores produced, receptors, and finally the way iron homeostasis is regulated in P. aeruginosa, P. syringae, P. putida, and P. fluorescens, will be presented and, when possible, put in relation with the lifestyle and the ecological niche. PMID:20352420

  14. Physiological, biomass elemental composition and proteomic analyses of Escherichia coli ammonium-limited chemostat growth, and comparison with iron- and glucose-limited chemostat growth

    PubMed Central

    Folsom, James Patrick

    2015-01-01

    Escherichia coli physiological, biomass elemental composition and proteome acclimations to ammonium-limited chemostat growth were measured at four levels of nutrient scarcity controlled via chemostat dilution rate. These data were compared with published iron- and glucose-limited growth data collected from the same strain and at the same dilution rates to quantify general and nutrient-specific responses. Severe nutrient scarcity resulted in an overflow metabolism with differing organic byproduct profiles based on limiting nutrient and dilution rate. Ammonium-limited cultures secreted up to 35  % of the metabolized glucose carbon as organic byproducts with acetate representing the largest fraction; in comparison, iron-limited cultures secreted up to 70  % of the metabolized glucose carbon as lactate, and glucose-limited cultures secreted up to 4  % of the metabolized glucose carbon as formate. Biomass elemental composition differed with nutrient limitation; biomass from ammonium-limited cultures had a lower nitrogen content than biomass from either iron- or glucose-limited cultures. Proteomic analysis of central metabolism enzymes revealed that ammonium- and iron-limited cultures had a lower abundance of key tricarboxylic acid (TCA) cycle enzymes and higher abundance of key glycolysis enzymes compared with glucose-limited cultures. The overall results are largely consistent with cellular economics concepts, including metabolic tradeoff theory where the limiting nutrient is invested into essential pathways such as glycolysis instead of higher ATP-yielding, but non-essential, pathways such as the TCA cycle. The data provide a detailed insight into ecologically competitive metabolic strategies selected by evolution, templates for controlling metabolism for bioprocesses and a comprehensive dataset for validating in silico representations of metabolism. PMID:26018546

  15. Physiological, biomass elemental composition and proteomic analyses of Escherichia coli ammonium-limited chemostat growth, and comparison with iron- and glucose-limited chemostat growth.

    PubMed

    Folsom, James Patrick; Carlson, Ross P

    2015-08-01

    Escherichia coli physiological, biomass elemental composition and proteome acclimations to ammonium-limited chemostat growth were measured at four levels of nutrient scarcity controlled via chemostat dilution rate. These data were compared with published iron- and glucose-limited growth data collected from the same strain and at the same dilution rates to quantify general and nutrient-specific responses. Severe nutrient scarcity resulted in an overflow metabolism with differing organic byproduct profiles based on limiting nutrient and dilution rate. Ammonium-limited cultures secreted up to 35% of the metabolized glucose carbon as organic byproducts with acetate representing the largest fraction; in comparison, iron-limited cultures secreted up to 70 % of the metabolized glucose carbon as lactate, and glucose-limited cultures secreted up to 4% of the metabolized glucose carbon as formate. Biomass elemental composition differed with nutrient limitation; biomass from ammonium-limited cultures had a lower nitrogen content than biomass from either iron- or glucose-limited cultures. Proteomic analysis of central metabolism enzymes revealed that ammonium- and iron-limited cultures had a lower abundance of key tricarboxylic acid (TCA) cycle enzymes and higher abundance of key glycolysis enzymes compared with glucose-limited cultures. The overall results are largely consistent with cellular economics concepts, including metabolic tradeoff theory where the limiting nutrient is invested into essential pathways such as glycolysis instead of higher ATP-yielding, but non-essential, pathways such as the TCA cycle. The data provide a detailed insight into ecologically competitive metabolic strategies selected by evolution, templates for controlling metabolism for bioprocesses and a comprehensive dataset for validating in silico representations of metabolism. PMID:26018546

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

    PubMed

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

    2014-01-01

    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. PMID:24864106

  17. [Iron metabolism: current concepts of an essential micronutrient].

    PubMed

    Boccio, Jose; Salgueiro, Jimena; Lysionek, Alexis; Zubillaga, Marcela; Goldman, Cinthia; Weill, Ricardo; Caro, Ricardo

    2003-06-01

    Iron is an essential micronutrient involved in multiple biochemical and physiological process. In this review we discuss the most relevant aspect of its metabolism in order to reach a better comprehension of the relevant roll that this micronutrient plays in human health. PMID:14528601

  18. Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

    PubMed Central

    Daugherty, Ana M; Raz, Naftali

    2015-01-01

    Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology. PMID:26248580

  19. Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation

    PubMed Central

    Martelli, Alain; Puccio, Hélène

    2014-01-01

    Friedreich ataxia (FRDA) is the most common recessive ataxia in the Caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia frequently associating cardiomyopathy. The disease results from decreased expression of the FXN gene coding for the mitochondrial protein frataxin. Early histological and biochemical study of the pathophysiology in patient's samples revealed that dysregulation of iron metabolism is a key feature of the disease, mainly characterized by mitochondrial iron accumulation and by decreased activity of iron-sulfur cluster enzymes. In the recent past years, considerable progress in understanding the function of frataxin has been provided through cellular and biochemical approaches, pointing to the primary role of frataxin in iron-sulfur cluster biogenesis. However, why and how the impact of frataxin deficiency on this essential biosynthetic pathway leads to mitochondrial iron accumulation is still poorly understood. Herein, we review data on both the primary function of frataxin and the nature of the iron metabolism dysregulation in FRDA. To date, the pathophysiological implication of the mitochondrial iron overload in FRDA remains to be clarified. PMID:24917819

  20. Iron homeostasis and responses to iron limitation in extreme acidophiles from the Ferroplasma genus.

    PubMed

    Potrykus, Joanna; Jonna, Venkateswara Rao; Dopson, Mark

    2011-01-01

    Extremely acidophilic archaea from the genus Ferroplasma inhabit iron-rich biomining environments and are important constituents of naturally occurring microbial consortia that catalyze the production of acid mine drainage. A combined bioinformatic, transcript profiling, and proteomic approach was used to elucidate iron homeostasis mechanisms in "F. acidarmanus" Fer1 and F. acidiphilum Y(T) . Bioinformatic analysis of the "F. acidarmanus" Fer1 genome sequence revealed genes encoding proteins hypothesized to be involved in iron-dependent gene regulation and siderophore biosynthesis; the Fhu and NRAMP cation acquisition systems; iron storage proteins; and the SUF machinery for the biogenesis of Fe-S clusters. A subset of homologous genes was identified on the F. acidiphilum Y(T) chromosome by direct PCR probing. In both strains, some of the genes appeared to be regulated in a ferrous/ferric iron-dependent manner, as indicated by RT-PCR. A detailed gel-based proteomics analysis of responses to iron depletion showed that a putative isochorismatase, presumably involved in siderophore biosynthesis, and the SufBCD system were upregulated under iron-limiting conditions. No evidence was obtained for iron sparing response during iron limitation. This study constitutes the first detailed investigation of iron homeostasis in extremely acidophilic archaea. PMID:21182194

  1. Proteomic Analysis Reveals That Iron Availability Alters the Metabolic Status of the Pathogenic Fungus Paracoccidioides brasiliensis

    PubMed Central

    Parente, Ana F. A.; Bailão, Alexandre M.; Borges, Clayton L.; Parente, Juliana A.; Magalhães, Adriana D.; Ricart, Carlos A. O.; Soares, Célia M. A.

    2011-01-01

    Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM). The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D) gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways. PMID:21829521

  2. HERC2 Targets the Iron Regulator FBXL5 for Degradation and Modulates Iron Metabolism

    PubMed Central

    Moroishi, Toshiro; Yamauchi, Takayoshi; Nishiyama, Masaaki; Nakayama, Keiichi I.

    2014-01-01

    FBXL5 (F-box and leucine-rich repeat protein 5) is the F-box protein subunit of, and therefore responsible for substrate recognition by, the SCFFBXL5 ubiquitin-ligase complex, which targets iron regulatory protein 2 (IRP2) for proteasomal degradation. IRP2 plays a central role in the maintenance of cellular iron homeostasis in mammals through posttranscriptional regulation of proteins that contribute to control of the intracellular iron concentration. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo, given that mice lacking FBXL5 die during early embryogenesis as a result of unrestrained IRP2 activity and oxidative stress attributable to excessive iron accumulation. Despite its pivotal role in the control of iron homeostasis, however, little is known of the upstream regulation of FBXL5 activity. We now show that FBXL5 undergoes constitutive ubiquitin-dependent degradation at the steady state. With the use of a proteomics approach to the discovery of proteins that regulate the stability of FBXL5, we identified the large HECT-type ubiquitin ligase HERC2 (HECT and RLD domain containing E3 ubiquitin protein ligase 2) as an FBXL5-associated protein. Inhibition of the HERC2-FBXL5 interaction or depletion of endogenous HERC2 by RNA interference resulted in the stabilization of FBXL5 and a consequent increase in its abundance. Such accumulation of FBXL5 in turn led to a decrease in the intracellular content of ferrous iron. Our results thus suggest that HERC2 regulates the basal turnover of FBXL5, and that this ubiquitin-dependent degradation pathway contributes to the control of mammalian iron metabolism. PMID:24778179

  3. HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism.

    PubMed

    Moroishi, Toshiro; Yamauchi, Takayoshi; Nishiyama, Masaaki; Nakayama, Keiichi I

    2014-06-01

    FBXL5 (F-box and leucine-rich repeat protein 5) is the F-box protein subunit of, and therefore responsible for substrate recognition by, the SCF(FBXL5) ubiquitin-ligase complex, which targets iron regulatory protein 2 (IRP2) for proteasomal degradation. IRP2 plays a central role in the maintenance of cellular iron homeostasis in mammals through posttranscriptional regulation of proteins that contribute to control of the intracellular iron concentration. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo, given that mice lacking FBXL5 die during early embryogenesis as a result of unrestrained IRP2 activity and oxidative stress attributable to excessive iron accumulation. Despite its pivotal role in the control of iron homeostasis, however, little is known of the upstream regulation of FBXL5 activity. We now show that FBXL5 undergoes constitutive ubiquitin-dependent degradation at the steady state. With the use of a proteomics approach to the discovery of proteins that regulate the stability of FBXL5, we identified the large HECT-type ubiquitin ligase HERC2 (HECT and RLD domain containing E3 ubiquitin protein ligase 2) as an FBXL5-associated protein. Inhibition of the HERC2-FBXL5 interaction or depletion of endogenous HERC2 by RNA interference resulted in the stabilization of FBXL5 and a consequent increase in its abundance. Such accumulation of FBXL5 in turn led to a decrease in the intracellular content of ferrous iron. Our results thus suggest that HERC2 regulates the basal turnover of FBXL5, and that this ubiquitin-dependent degradation pathway contributes to the control of mammalian iron metabolism. PMID:24778179

  4. Human macrophage hemoglobin-iron metabolism in vitro

    SciTech Connect

    Custer, G.; Balcerzak, S.; Rinehart, J.

    1982-01-01

    An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of /sup 59/Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of /sup 59/Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in /sup 59/Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models.

  5. Iron metabolism in aerobes: managing ferric iron hydrolysis and ferrous iron autoxidation

    PubMed Central

    Kosman, Daniel J.

    2012-01-01

    Aerobes and anaerobes alike express a plethora of essential iron enzymes; in the resting state, the iron atom(s) in these proteins are in the ferrous state. For aerobes, ferric iron is the predominant environmental valence form which, given ferric iron’s aqueous chemistry, occurs as ‘rust’, insoluble, bio-inert polymeric ferric oxide that results from the hydrolysis of [Fe(H2O)6]3+. Mobilizing this iron requires bio-ferrireduction which in turn requires managing the rapid autoxidation of the resulting FeII which occurs at pH > 6. This review examines the aqueous redox chemistry of iron and the mechanisms evolved in aerobes to suppress the ‘rusting out’ of FeIII and the ROS-generating autoxidation of FeII so as to make this metal ion available as the most ubiquitous prosthetic group in metallobiology. PMID:23264695

  6. Lipid composition and transcriptional response of Mycobacterium tuberculosis grown under iron-limitation in continuous culture: identification of a novel wax ester

    PubMed Central

    Bacon, Joanna; Dover, Lynn G.; Hatch, Kim A.; Zhang, Yi; Gomes, Jessica M.; Kendall, Sharon; Wernisch, Lorenz; Stoker, Neil G.; Butcher, Philip D.; Besra, Gurdyal S.; Marsh, Philip D.

    2011-01-01

    The low level of available iron in vivo is a major obstacle for microbial pathogens and is a stimulus for the expression of virulence genes. In this study, Mycobacterium tuberculosis H37Rv was grown aerobically in the presence of limited iron availability in chemostat culture to determine the physiological response of the organism to iron-limitation. A previously unidentified wax ester accumulated under iron-limited growth, and changes in the abundance of triacylglycerol and menaquinone were also observed between iron-replete and iron-limited chemostat cultures. DNA microarray analysis revealed differential expression of genes involved in glycerolipid metabolism and isoprenoid quinone biosynthesis, providing some insight into the underlying genetic changes that correlate with cell-wall lipid profiles of M. tuberculosis growing in an iron-limited environment. PMID:17464057

  7. Derepression of the Azotobacter vinelandii siderophore system, using iron-containing minerals to limit iron repletion.

    PubMed Central

    Page, W J; Huyer, M

    1984-01-01

    Azotobacter vinelandii solubilized iron from certain minerals using only dihydroxybenzoic acid, which appeared to be produced constitutively. Solubilization of iron from other minerals required dihydroxybenzoic acid and the siderophore N,N'-bis-(2,3- dihydroxybenzoyl )-L-lysine ( azotochelin ) or these chelators plus the yellow-green fluorescent siderophore azotobactin . In addition to this sequential production of siderophores, cells also demonstrated partial to hyperproduction relative to the iron-limited control. The iron sources which caused partial derepression of the siderophores caused derepression of all the high-molecular-weight iron-repressible outer membrane proteins except a 77,000-molecular-weight protein, which appeared to be coordinated with azotobactin production. Increased siderophore production correlated with increased production of outer membrane proteins with molecular weights of 93,000, 85,000, and 77,000, but an 81,000-molecular-weight iron-repressible protein appeared at a constant level despite the degree of derepression. When iron was readily available, it appeared to complex with a 60,000-molecular-weight protein believed to form a surface layer on the A. vinelandii cell. Images PMID:6233258

  8. Development of a robust marine ecosystem model to predict the role of iron in biogeochemical cycles: A comparison of results for iron-replete and iron-limited areas, and the SOIREE iron-enrichment experiment

    NASA Astrophysics Data System (ADS)

    Fasham, M. J. R.; Flynn, K. J.; Pondaven, P.; Anderson, T. R.; Boyd, P. W.

    2006-02-01

    A new mixed layer multi-nutrient ecosystem model, incorporating diatoms, non-diatoms and zooplankton, is described that models the role of iron in marine biogeochemical cycles. The internal cell biochemistry of the phytoplankton is modelled using the mechanistic model of Flynn [2001. A mechanistic model for describing dynamic multi-nutrient, light, temperature interactions in phytoplankton. Journal of Plankton Research 23, 977-997] in which the internal cell concentrations of chlorophyll, nitrogen, silica, and iron are all dynamic variables that respond to external nutrient concentrations and light levels. Iron stress in phytoplankton feeds back into chlorophyll synthesis and changes in photosynthetic unit (PSU) size, thereby reducing their growth rate. Because diatom silicon metabolism is inextricably linked with cell division, diatom population density (cell m -3) is modelled as well as C biomass. An optimisation technique was used to fit the model to three time-series datasets at Biotrans (47°N, 20°W) and Kerfix (50°40'S, 68°25'E) and the observations for the Southern Ocean Iron-Release Experiment (SOIREE) iron-enrichment experiment (61°S, 140°E). The model gives realistic simulations of the annual cycles of nutrients, phytoplankton, and primary production at Biotrans and Kerfix and can also accurately simulate an iron fertilisation experiment. Specifically, the model predicts the high values of diatom Si:N and Si:C ratios observed in areas where iron is a limiting factor on algal growth. In addition, the model results at Kerfix confirm previous suggestions that underwater light levels have a more limiting effect on phytoplankton growth than iron supply. The model is also used to calculate C budgets and C and Si export from the mixed layer. The implications of these results for developing biogeochemical models incorporating the role of iron are discussed.

  9. Arsenic release metabolically limited to permanently water-saturated soil in Mekong Delta

    NASA Astrophysics Data System (ADS)

    Stuckey, Jason W.; Schaefer, Michael V.; Kocar, Benjamin D.; Benner, Shawn G.; Fendorf, Scott

    2016-01-01

    Microbial reduction of arsenic-bearing iron oxides in the deltas of South and Southeast Asia produces widespread arsenic-contaminated groundwater. Organic carbon is abundant both at the surface and within aquifers, but the source of organic carbon used by microbes in the reduction and release of arsenic has been debated, as has the wetland type and sedimentary depth where release occurs. Here we present data from fresh-sediment incubations, in situ model sediment incubations and a controlled field experiment with manipulated wetland hydrology and organic carbon inputs. We find that in the minimally disturbed Mekong Delta, arsenic release is limited to near-surface sediments of permanently saturated wetlands where both organic carbon and arsenic-bearing solids are sufficiently reactive for microbial oxidation of organic carbon and reduction of arsenic-bearing iron oxides. In contrast, within the deeper aquifer or seasonally saturated sediments, reductive dissolution of iron oxides is observed only when either more reactive exogenous forms of iron oxides or organic carbon are added, revealing a potential thermodynamic restriction to microbial metabolism. We conclude that microbial arsenic release is limited by the reactivity of arsenic-bearing iron oxides with respect to native organic carbon, but equally limited by organic carbon reactivity with respect to the native arsenic-bearing iron oxides.

  10. Iron deprivation results in a rapid but not sustained increase of the expression of genes involved in iron metabolism and sulfate uptake in tomato (Solanum lycopersicum L.) seedlings.

    PubMed

    Paolacci, Anna Rita; Celletti, Silvia; Catarcione, Giulio; Hawkesford, Malcolm J; Astolfi, Stefania; Ciaffi, Mario

    2014-01-01

    Characterization of the relationship between sulfur and iron in both Strategy I and Strategy II plants, has proven that low sulfur availability often limits plant capability to cope with iron shortage. Here it was investigated whether the adaptation to iron deficiency in tomato (Solanum lycopersicum L.) plants was associated with an increased root sulfate uptake and translocation capacity, and modified dynamics of total sulfur and thiols accumulation between roots and shoots. Most of the tomato sulfate transporter genes belonging to Groups 1, 2, and 4 were significantly upregulated in iron-deficient roots, as it commonly occurs under S-deficient conditions. The upregulation of the two high affinity sulfate transporter genes, SlST1.1 and SlST1.2, by iron deprivation clearly suggests an increased root capability to take up sulfate. Furthermore, the upregulation of the two low affinity sulfate transporter genes SlST2.1 and SlST4.1 in iron-deficient roots, accompanied by a substantial accumulation of total sulfur and thiols in shoots of iron-starved plants, likely supports an increased root-to-shoot translocation of sulfate. Results suggest that tomato plants exposed to iron-deficiency are able to change sulfur metabolic balance mimicking sulfur starvation responses to meet the increased demand for methionine and its derivatives, allowing them to cope with this stress. PMID:24119307

  11. Effects of Iron and Nitrogen Limitation on Sulfur Isotope Fractionation during Microbial Sulfate Reduction

    PubMed Central

    Ono, Shuhei; Bosak, Tanja

    2012-01-01

    Sulfate-reducing microbes utilize sulfate as an electron acceptor and produce sulfide that is depleted in heavy isotopes of sulfur relative to sulfate. Thus, the distribution of sulfur isotopes in sediments can trace microbial sulfate reduction (MSR), and it also has the potential to reflect the physiology of sulfate-reducing microbes. This study investigates the relationship between the availability of iron and reduced nitrogen and the magnitude of S-isotope fractionation during MSR by a marine sulfate-reducing bacterium, DMSS-1, a Desulfovibrio species, isolated from salt marsh in Cape Cod, MA. Submicromolar levels of iron increase sulfur isotope fractionation by about 50% relative to iron-replete cultures of DMSS-1. Iron-limited cultures also exhibit decreased cytochrome c-to-total protein ratios and cell-specific sulfate reduction rates (csSRR), implying changes in the electron transport chain that couples carbon and sulfur metabolisms. When DMSS-1 fixes nitrogen in ammonium-deficient medium, it also produces larger fractionation, but it occurs at faster csSRRs than in the ammonium-replete control cultures. The energy and reducing power required for nitrogen fixation may be responsible for the reverse trend between S-isotope fractionation and csSRR in this case. Iron deficiency and nitrogen fixation by sulfate-reducing microbes may lead to the large observed S-isotope effects in some euxinic basins and various anoxic sediments. PMID:23001667

  12. Sleep disorders: A review of the interface between restless legs syndrome and iron metabolism

    PubMed Central

    Daubian-Nosé, Paulo; Frank, Miriam K.; Esteves, Andrea Maculano

    2014-01-01

    Restless legs syndrome (RLS) is characterized by unpleasant sensations mainly in the legs. 43% of RLS-associated conditions have also been associated with systemic iron deficiency. The objective of this study was to review in the literature the relationship between iron metabolism and RLS. With an initial search using the keywords combination “Iron Metabolism OR Iron Deficiency AND Restless Legs Syndrome,” 145 articles were screened, and 20 articles were selected. Few studies were found for this review in the period of 2001–2014, however, the correlation between RLS and iron was evident. PMID:26483934

  13. Update on iron metabolism and molecular perspective of common genetic and acquired disorder, hemochromatosis.

    PubMed

    Yun, Seongseok; Vincelette, Nicole D

    2015-07-01

    Iron is an essential component of erythropoiesis and its metabolism is tightly regulated by a variety of internal and external cues including iron storage, tissue hypoxia, inflammation and degree of erythropoiesis. There has been remarkable improvement in our understanding of the molecular mechanisms of iron metabolism past decades. The classical model of iron metabolism with iron response element/iron response protein (IRE/IRP) is now extended to include hepcidin model. Endogenous and exogenous signals funnel down to hepcidin via wide range of signaling pathways including Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3), Bone Morphogenetic Protein/Hemojuvelin/Mothers Against Decapentaplegic Homolog (BMP/HJV/SMAD), and Von Hippel Lindau/Hypoxia-inducible factor/Erythropoietin (VHL/HIF/EPO), then relay to ferroportin, which directly regulates intra- and extracellular iron levels. The successful molecular delineation of iron metabolism further enhanced our understanding of common genetic and acquired disorder, hemochromatosis. The majority of the hereditary hemochromatosis (HH) patients are now shown to have mutations in the genes coding either upstream or downstream proteins of hepcidin, resulting in iron overload. The update on hepcidin centered mechanisms of iron metabolism and their clinical perspective in hemochromatosis will be discussed in this review. PMID:25737209

  14. Influence of microRNA on the Maintenance of Human Iron Metabolism

    PubMed Central

    Davis, McKale; Clarke, Stephen

    2013-01-01

    Iron is an essential nutrient critical for many cellular functions including DNA synthesis, ATP generation, and cellular proliferation. Though essential, excessive iron may contribute to the generation of free radicals capable of damaging cellular lipids, proteins, and nucleic acids. As such, the maintenance and control of cellular iron homeostasis is critical to prevent either iron deficiency or iron toxicity conditions. The maintenance of cellular iron homeostasis is largely coordinated by a family of cytosolic RNA binding proteins known as Iron Regulatory Proteins (IRP) that function to post-transcriptionally control the translation and/or stability of mRNA encoding proteins required for iron uptake, storage, transport, and utilization. More recently, a class of small non-coding RNA known as microRNA (miRNA) has also been implicated in the control of iron metabolism. To date, miRNA have been demonstrated to post-transcriptionally regulate the expression of genes associated with iron acquisition (transferrin receptor and divalent metal transporter), iron export (ferroportin), iron storage (ferritin), iron utilization (ISCU), and coordination of systemic iron homeostasis (HFE and hemojevelin). Given the diversity of miRNA and number of potential mRNA targets, characterizing factors that contribute to alterations in miRNA expression, biogenesis, and processing will enhance our understanding of mechanisms by which cells respond to changes in iron demand and/or iron availability to control cellular iron homeostasis. PMID:23846788

  15. Like iron in the blood of the people: the requirement for heme trafficking in iron metabolism

    PubMed Central

    Korolnek, Tamara; Hamza, Iqbal

    2014-01-01

    Heme is an iron-containing porphyrin ring that serves as a prosthetic group in proteins that function in diverse metabolic pathways. Heme is also a major source of bioavailable iron in the human diet. While the synthesis of heme has been well-characterized, the pathways for heme trafficking remain poorly understood. It is likely that heme transport across membranes is highly regulated, as free heme is toxic to cells. This review outlines the requirement for heme delivery to various subcellular compartments as well as possible mechanisms for the mobilization of heme to these compartments. We also discuss how these trafficking pathways might function during physiological events involving inter- and intra-cellular mobilization of heme, including erythropoiesis, erythrophagocytosis, heme absorption in the gut, as well as heme transport pathways supporting embryonic development. Lastly, we aim to question the current dogma that heme, in toto, is not mobilized from one cell or tissue to another, outlining the evidence for these pathways and drawing parallels to other well-accepted paradigms for copper, iron, and cholesterol homeostasis. PMID:24926267

  16. Coupling Heme and Iron Metabolism via Ferritin H Chain

    PubMed Central

    2014-01-01

    Abstract Significance: Inflammation and immunity can be associated with varying degrees of heme release from hemoproteins, eventually leading to cellular and tissue iron (Fe) overload, oxidative stress, and tissue damage. Presumably, these deleterious effects contribute to the pathogenesis of systemic infections. Recent Advances: Heme release from hemoglobin sensitizes parenchyma cells to undergo programmed cell death in response to proinflammatory cytokines, such as tumor necrosis factor. This cytotoxic effect is driven by a mechanism involving intracellular accumulation of free radicals, which sustain the activation of the c-Jun N-terminal kinase (JNK) signaling transduction pathway. While heme catabolism by heme oxygenase-1 (HO-1) prevents programmed cell death, this cytoprotective effect requires the co-expression of ferritin H (heart/heavy) chain (FTH), which controls the pro-oxidant effect of labile Fe released from the protoporphyrin IX ring of heme. This antioxidant effect of FTH restrains JNK activation, whereas JNK activation inhibits FTH expression, a cross talk that controls metabolic adaptation to cellular Fe overload associated with systemic infections. Critical Issues and Future Directions: Identification and characterization of the mechanisms via which FTH provides metabolic adaptation to tissue Fe overload should provide valuable information to our current understanding of the pathogenesis of systemic infections as well as other immune-mediated inflammatory diseases. Antioxid. Redox Signal. 20, 1754–1769. PMID:24124891

  17. New strategies to target iron metabolism for the treatment of beta thalassemia.

    PubMed

    Oikonomidou, Paraskevi Rea; Casu, Carla; Rivella, Stefano

    2016-03-01

    Iron is one of the most abundant elements in the Earth and a fundamental component of enzymes and other proteins that participate in a wide range of biological processes. As the human body has no mechanisms to eliminate the excess of iron, its metabolism needs to be tightly controlled in order to avoid all the sequelae associated with high iron levels. Iron overload is the main cause of morbidity and mortality in beta thalassemia. The master regulator of iron homeostasis, hepcidin, is chronically repressed in this disorder, leading to increased intestinal iron absorption and consequent iron overload. Many groups have focused on obtaining a better understanding of the pathways involved in iron regulation. New molecules have recently been synthesized and used in animal models of dysregulated iron metabolism, demonstrating their ability to target and reduce iron load. Antisense oligonucleotides, as well as lipid nanoparticle-formulated small interfering RNAs and minihepcidins peptides, are novel agents that have already proved to be efficient in modulating iron metabolism in mouse models and are therefore promising candidates for the treatment of patients affected by iron disorders. PMID:26919168

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

    PubMed

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem; O'Brien, Edward J; Szubin, Richard; Palsson, Bernhard O

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response to iron availability using genome-wide measurements. Integrative data analysis reveals that a total of 81 genes in 42 transcription units are directly regulated by three different modes of Fur regulation, including apo- and holo-Fur activation and holo-Fur repression. We show that Fur connects iron transport and utilization enzymes with negative-feedback loop pairs for iron homeostasis. In addition, direct involvement of Fur in the regulation of DNA synthesis, energy metabolism and biofilm development is found. These results show how Fur exhibits a comprehensive regulatory role affecting many fundamental cellular processes linked to iron metabolism in order to coordinate the overall response of E. coli to iron availability. PMID:25222563

  19. EXPLORING THE LIMITS TO LIGNINS' METABOLIC PLASTICITY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Just how far can lignification be pushed with the aim of improving wood processing (and possibly solid wood properties)? We will explore the limits to which the 3 traditional monolignols can be manipulated, but also broaden our scope to begin thinking about how the entire monomer pool for lignificat...

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

    PubMed Central

    Lane, Darius J. R.; Bae, Dong-Hun; Merlot, Angelica M.; Sahni, Sumit; Richardson, Des R.

    2015-01-01

    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. PMID:25835049

  1. Hepcidin and HFE protein: Iron metabolism as a target for the anemia of chronic kidney disease.

    PubMed

    Canavesi, Elena; Alfieri, Carlo; Pelusi, Serena; Valenti, Luca

    2012-12-01

    The anemia of chronic kidney disease and hemodialysis is characterized by chronic inflammation and release of cytokines, resulting in the upregulation of the iron hormone hepcidin, also increased by iron therapy and reduced glomerular filtration, with consequent reduction in iron absorption, recycling, and availability to the erythron. This response proves advantageous in the short-term to restrain iron availability to pathogens, but ultimately leads to severe anemia, and impairs the response to erythropoietin (Epo) and iron. Homozygosity for the common C282Y and H63D HFE polymorphisms influence iron metabolism by hampering hepcidin release by hepatocytes in response to increased iron stores, thereby resulting in inadequate inhibition of the activity of Ferroportin-1, inappropriately high iron absorption and recycling, and iron overload. However, in hemodialysis patients, carriage of HFE mutations may confer an adaptive benefit by decreasing hepcidin release in response to iron infusion and inflammation, thereby improving iron availability to erythropoiesis, anemia control, the response to Epo, and possibly survival. Therefore, anti-hepcidin therapies may improve anemia management in hemodialysis. However, HFE mutations directly favor hemoglobinization independently of hepcidin, and reduce macrophages activation in response to inflammation, whereas hepcidin might also play a beneficial anti-inflammatory and anti-microbic action during sepsis, so that direct inhibition of HFE-mediated regulation of iron metabolism may represent a valuable alternative therapeutic target. Genetic studies may offer a valuable tool to test these hypotheses and guide the research of new therapies. PMID:24175256

  2. Iron and the liver. Acute and long-term effects of iron-loading on hepatic haem metabolism.

    PubMed Central

    Bonkowsky, H L; Healey, J F; Sinclair, P R; Sinclair, J F; Pomeroy, J S

    1981-01-01

    We have determined the dose-response curves (100-900 mg of Fe/kg body wt.) and the time course over 84 days for the effects of a single injection of iron-dextran on rat hepatic 5-aminolaevulinate synthetase, cytochrome P-450, iron content, and GSH (reduced glutathione). Porphyrins in liver and urine have also been measured. (1) At 2 days after treatment, a dose of 500 mg of Fe/kg produced a 20-fold increase in iron concentration, which was maintained for 14 days. Total hepatic iron remained constant over 63 days, falling slightly by 84 days. (2) The activity of 5-aminolaevulinate synthetase was maximally increased (6-fold) 12-24 h after iron treatment. By 48 h the activity fell to less than twice the control value and thereafter remained slightly above the control value (1.1-1.5-fold) until 84 days after iron treatment. Liver GSH concentrations were unaffected by iron. Porphyrins in liver and urine were either unchanged or decreased. (3) Hepatic cytochrome P-450 decreased after iron treatment to a minimum (63% of control) at 48 h after iron administration and gradually returned to the control value by 28 days. (4) Iron-dextran potentiated 2 allyl-2-isopropyl-acetamide-induced synthesis of hepatic 5-aminolaevulinate. Potentiation occurred if the drug was given at the same time or 36 h after iron administration, but did not occur if the drug was given 14 or 64 days after iron administration. (5) The results are discussed in relation to proposed mechanisms for the effects of iron on hepatic haem metabolism. PMID:7306080

  3. Limits to Success. The Iron Law of Verhulst

    NASA Astrophysics Data System (ADS)

    Kunsch, P. L.

    In this chapter we develop the point of view that Verhulst is a major initiator of systems thinking. His logistic equation is a system archetype, i.e. a simple system built with few feedback loops. In the Fifth Discipline [19] Peter Senge calls this particular archetype "Limits to Success". It can also be called the "Iron law of Verhulst", expressing that trees can never grow to heaven. In a deeper analysis this equation illustrates the shifting loop dominance, one of the basic principles of system dynamics. The basic message is that the combination of some few archetypes, like the logistic growth, can afford valuable insight into many complex systems such as the economy, environment, organisations, etc. This fruitful concept is illustrated by a simple model in behavioural finance describing the equity price evolution, and based on the interplay of three main growth archetypes: "Limits to Success", "Tragedy of the Commons", and "Balancing Loop with Delay".

  4. The effect of BCG on iron metabolism in the early neonatal period: A controlled trial in Gambian neonates.

    PubMed

    Prentice, Sarah; Jallow, Momodou W; Prentice, Andrew M

    2015-06-12

    Bacillus Calmette-Guerin (BCG) vaccination has been reported to protect neonates from non-tuberculous pathogens, but no biological mechanism to explain such effects is known. We hypothesised that BCG produces broad-spectrum anti-microbial protection via a hepcidin-mediated hypoferraemia, limiting iron availability for pathogens. To test this we conducted a trial in 120 Gambian neonates comparing iron status in the first 5-days of life after allocation to: (1) All routine vaccinations at birth (BCG/Oral Polio Vaccine (OPV)/Hepatitis B Vaccine (HBV)); (2) BCG delayed until after the study period (at day 5); and (3) All routine vaccinations delayed until after the study period. Vaccine regime at birth did not significantly impact on any measured parameter of iron metabolism. However, the ability to detect an effect of BCG on iron metabolism may have been limited by short follow-up time and high activation of the inflammatory-iron axis in the study population. PMID:25959747

  5. Metabolic Factors Limiting Performance in Marathon Runners

    PubMed Central

    Rapoport, Benjamin I.

    2010-01-01

    Each year in the past three decades has seen hundreds of thousands of runners register to run a major marathon. Of those who attempt to race over the marathon distance of 26 miles and 385 yards (42.195 kilometers), more than two-fifths experience severe and performance-limiting depletion of physiologic carbohydrate reserves (a phenomenon known as ‘hitting the wall’), and thousands drop out before reaching the finish lines (approximately 1–2% of those who start). Analyses of endurance physiology have often either used coarse approximations to suggest that human glycogen reserves are insufficient to fuel a marathon (making ‘hitting the wall’ seem inevitable), or implied that maximal glycogen loading is required in order to complete a marathon without ‘hitting the wall.’ The present computational study demonstrates that the energetic constraints on endurance runners are more subtle, and depend on several physiologic variables including the muscle mass distribution, liver and muscle glycogen densities, and running speed (exercise intensity as a fraction of aerobic capacity) of individual runners, in personalized but nevertheless quantifiable and predictable ways. The analytic approach presented here is used to estimate the distance at which runners will exhaust their glycogen stores as a function of running intensity. In so doing it also provides a basis for guidelines ensuring the safety and optimizing the performance of endurance runners, both by setting personally appropriate paces and by prescribing midrace fueling requirements for avoiding ‘the wall.’ The present analysis also sheds physiologically principled light on important standards in marathon running that until now have remained empirically defined: The qualifying times for the Boston Marathon. PMID:20975938

  6. Cellular hallmarks reveal restricted aerobic metabolism at thermal limits

    PubMed Central

    Neves, Aitana; Busso, Coralie; Gönczy, Pierre

    2015-01-01

    All organisms live within a given thermal range, but little is known about the mechanisms setting the limits of this range. We uncovered cellular features exhibiting signature changes at thermal limits in Caenorhabditis elegans embryos. These included changes in embryo size and shape, which were also observed in Caenorhabditis briggsae, indicating evolutionary conservation. We hypothesized that such changes could reflect restricted aerobic capacity at thermal limits. Accordingly, we uncovered that relative respiration in C. elegans embryos decreases at the thermal limits as compared to within the thermal range. Furthermore, by compromising components of the respiratory chain, we demonstrated that the reliance on aerobic metabolism is reduced at thermal limits. Moreover, embryos thus compromised exhibited signature changes in size and shape already within the thermal range. We conclude that restricted aerobic metabolism at the thermal limits contributes to setting the thermal range in a metazoan organism. DOI: http://dx.doi.org/10.7554/eLife.04810.001 PMID:25929283

  7. The Ins and Outs of Bacterial Iron Metabolism

    PubMed Central

    Frawley, Elaine R.; Fang, Ferric C.

    2014-01-01

    Summary Iron is a critical nutrient for the growth and survival of most bacterial species. Accordingly, much attention has been paid to the mechanisms by which host organisms sequester iron from invading bacteria and how bacteria acquire iron from their environment. However, under oxidative stress conditions such as those encountered within phagocytic cells during the host immune response, iron is released from proteins and can act as a catalyst for Fenton chemistry to produce cytotoxic reactive oxygen species. The transitory efflux of free intracellular iron may be beneficial to bacteria under such conditions. The recent discovery of putative iron efflux transporters in Salmonella enterica serovar Typhimurium is discussed in the context of cellular iron homeostasis. PMID:25040830

  8. Changes in certain iron metabolism variables after a single blood donation.

    PubMed

    Liedén, G; Höglund, S; Ehn, L

    1975-01-01

    Signs of iron deficiency have been studied after the first blood donation in 11 healthy men. Six were given 100 mg iron daily, and five received placebo tablets. The total iron-binding capacity and iron absoprtion remained raised for more than 26 days, but had almost returned to the initial values after 70 days. A significant decrease in the stainable bone marrow iron could be shown in all subjects after 26 days; later some restitution was seen in subjects given iron supplements, but not in those given placebo. As the restitution times are long, the interval after blood donation must be taken into account when judging iron metabolism variables in active donors. PMID:1092130

  9. Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis

    PubMed Central

    Marty, Amber J.; Broman, Aimee T.; Zarnowski, Robert; Dwyer, Teigan G.; Bond, Laura M.; Lounes-Hadj Sahraoui, Anissa; Fontaine, Joël; Ntambi, James M.; Keleş, Sündüz; Kendziorski, Christina; Gauthier, Gregory M.

    2015-01-01

    In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0–48 hours), gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition. PMID:26114571

  10. Regulation of Iron Metabolism by Hepcidin under Conditions of Inflammation*

    PubMed Central

    Schmidt, Paul J.

    2015-01-01

    Iron is a redox-active metal required as a cofactor in multiple metalloproteins essential for a host of life processes. The metal is highly toxic when present in excess and must be strictly regulated to prevent tissue and organ damage. Hepcidin, a molecule first characterized as an antimicrobial peptide, plays a critical role in the regulation of iron homeostasis. Multiple stimuli positively influence the expression of hepcidin, including iron, inflammation, and infection by pathogens. In this Minireview, I will discuss how inflammation regulates hepcidin transcription, allowing for sufficient concentrations of iron for organismal needs while sequestering the metal from infectious pathogens. PMID:26055723

  11. The Crossroads of Iron with Hypoxia and Cellular Metabolism. Implications in the Pathobiology of Pulmonary Hypertension

    PubMed Central

    Graham, Brian B.; Rouault, Tracey C.; Tuder, Rubin M.

    2014-01-01

    The pathologic hallmark of pulmonary arterial hypertension (PAH) is pulmonary vascular remodeling, characterized by endothelial cell proliferation, smooth muscle hypertrophy, and perivascular inflammation, ultimately contributing to increased pulmonary arterial pressures. Several recent studies have observed that iron deficiency in patients with various forms of PAH is associated with worsened clinical outcome. Iron plays a key role in many cellular processes regulating the response to hypoxia, oxidative stress, cellular proliferation, and cell metabolism. Given the potential importance of iron supplementation in patients with the disease and the broad cellular functions of iron, we review its role in processes that pertain to PAH. PMID:24988529

  12. IscR of Rhodobacter sphaeroides functions as repressor of genes for iron-sulfur metabolism and represents a new type of iron-sulfur-binding protein

    PubMed Central

    Remes, Bernhard; Eisenhardt, Benjamin D; Srinivasan, Vasundara; Klug, Gabriele

    2015-01-01

    IscR proteins are known as transcriptional regulators for Fe–S biogenesis. In the facultatively phototrophic bacterium, Rhodobacter sphaeroides IscR is the product of the first gene in the isc-suf operon. A major role of IscR in R. sphaeroides iron-dependent regulation was suggested in a bioinformatic study (Rodionov et al., PLoS Comput Biol 2:e163, 2006), which predicted a binding site in the upstream regions of several iron uptake genes, named Iron-Rhodo-box. Most known IscR proteins have Fe–S clusters featuring (Cys)3(His)1 ligation. However, IscR proteins from Rhodobacteraceae harbor only a single-Cys residue and it was considered unlikely that they can ligate an Fe–S cluster. In this study, the role of R. sphaeroides IscR as transcriptional regulator and sensor of the Fe–S cluster status of the cell was analyzed. A mutant lacking IscR is more impaired in growth under iron limitation than the wild-type and exhibits significantly increased ROS levels in iron-replete and iron-deplete conditions. Expression studies reveal that R. sphaeroides IscR in its cluster-bound form functions as transcriptional repressor of genes involved in iron metabolism by direct binding to the promoter region of genes preceded by the motif. A total of 110 genes are directly or indirectly affected by IscR. Furthermore, IscR possesses a unique Fe–S cluster ligation scheme with only a single cysteine involved. PMID:26235649

  13. IscR of Rhodobacter sphaeroides functions as repressor of genes for iron-sulfur metabolism and represents a new type of iron-sulfur-binding protein.

    PubMed

    Remes, Bernhard; Eisenhardt, Benjamin D; Srinivasan, Vasundara; Klug, Gabriele

    2015-10-01

    IscR proteins are known as transcriptional regulators for Fe-S biogenesis. In the facultatively phototrophic bacterium, Rhodobacter sphaeroides IscR is the product of the first gene in the isc-suf operon. A major role of IscR in R. sphaeroides iron-dependent regulation was suggested in a bioinformatic study (Rodionov et al., PLoS Comput Biol 2:e163, 2006), which predicted a binding site in the upstream regions of several iron uptake genes, named Iron-Rhodo-box. Most known IscR proteins have Fe-S clusters featuring (Cys)3 (His)1 ligation. However, IscR proteins from Rhodobacteraceae harbor only a single-Cys residue and it was considered unlikely that they can ligate an Fe-S cluster. In this study, the role of R. sphaeroides IscR as transcriptional regulator and sensor of the Fe-S cluster status of the cell was analyzed. A mutant lacking IscR is more impaired in growth under iron limitation than the wild-type and exhibits significantly increased ROS levels in iron-replete and iron-deplete conditions. Expression studies reveal that R. sphaeroides IscR in its cluster-bound form functions as transcriptional repressor of genes involved in iron metabolism by direct binding to the promoter region of genes preceded by the motif. A total of 110 genes are directly or indirectly affected by IscR. Furthermore, IscR possesses a unique Fe-S cluster ligation scheme with only a single cysteine involved. PMID:26235649

  14. Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism.

    PubMed

    Pollak, Yulia; Mechlovich, Danit; Amit, Tamar; Bar-Am, Orit; Manov, Irena; Mandel, Silvia A; Weinreb, Orly; Meyron-Holtz, Esther G; Iancu, Theodore C; Youdim, Moussa B H

    2013-01-01

    Iron accumulation and iron-related oxidative stress are involved in several pathological conditions and provide a rationale for the development of iron chelators as novel promising therapeutic strategies. Thus, we have recently synthesized multifunctional non-toxic, brain permeable iron chelating compounds, M30 and HLA20, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelating moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we examined the hepatic regulatory effects of these novel compounds using two experimental approaches: chelation activity and glucose metabolism parameters. The present study demonstrated that M30 and HLA20 significantly decreased intracellular iron content and reduced ferritin expression levels in iron-loaded hepatoma Hep3B cells. In electron microscopy analysis, M30 was shown to reduce the electron-dense deposits of siderosomes by ~30 %, as well as down-regulate cytosolic ferritin particles observed in iron-overloaded cells. In vivo studies demonstrated that M30 administration (1 mg/kg, P.O. three times a week) reduced hepatic ferritin levels; increased hepatic insulin receptor and glucose transporter-1 levels and improved glucose tolerance in C57BL/6 mice and in a mouse model of type-2 diabetes, the ob/ob (leptin(-/-)). The results clearly indicate that the novel multifunctional drugs, especially M30, display significant capacity of chelating intracellular iron and regulating glucose metabolism parameters. Such effects can have therapeutic significance in conditions with abnormal local or systemic iron metabolism, including neurological diseases. PMID:22446839

  15. The Effect of Iron Limitation on the Transcriptome and Proteome of Pseudomonas fluorescens Pf-5

    PubMed Central

    Lim, Chee Kent; Hassan, Karl A.; Tetu, Sasha G.; Loper, Joyce E.; Paulsen, Ian T.

    2012-01-01

    One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels. PMID:22723948

  16. The effect of iron limitation on the transcriptome and proteome of Pseudomonas fluorescens Pf-5.

    PubMed

    Lim, Chee Kent; Hassan, Karl A; Tetu, Sasha G; Loper, Joyce E; Paulsen, Ian T

    2012-01-01

    One of the most important micronutrients for bacterial growth is iron, whose bioavailability in soil is limited. Consequently, rhizospheric bacteria such as Pseudomonas fluorescens employ a range of mechanisms to acquire or compete for iron. We investigated the transcriptomic and proteomic effects of iron limitation on P. fluorescens Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that genes encoding functions related to iron homeostasis, including pyoverdine and enantio-pyochelin biosynthesis, a number of TonB-dependent receptor systems, as well as some inner-membrane transporters, were significantly up-regulated in response to iron limitation. Transcription of a ribosomal protein L36-encoding gene was also highly up-regulated during iron limitation. Certain genes or proteins involved in biosynthesis of secondary metabolites such as 2,4-diacetylphloroglucinol (DAPG), orfamide A and pyrrolnitrin, as well as a chitinase, were over-expressed under iron-limited conditions. In contrast, we observed that expression of genes involved in hydrogen cyanide production and flagellar biosynthesis were down-regulated in an iron-depleted culture medium. Phenotypic tests revealed that Pf-5 had reduced swarming motility on semi-solid agar in response to iron limitation. Comparison of the transcriptomic data with the proteomic data suggested that iron acquisition is regulated at both the transcriptional and post-transcriptional levels. PMID:22723948

  17. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

    PubMed Central

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  18. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.

    PubMed

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-01-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

  19. Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin

    PubMed Central

    Yalcintepe, Leman; Halis, Emre

    2016-01-01

    Increased intracellular iron levels can both promote cell proliferation and death, as such; iron has a “two-sided effect” in the delicate balance of human health. Though the role of iron in the development of cancer remains unclear, investigations of iron chelators as anti-tumor agents have revealed promising results. Here, we investigated the influence of iron and desferrioxamine (DFO), the iron chelating agent on intracellular calcium in a human leukemia cell line, K562. Iron uptake is associated with increased reactive oxygen species (ROS) generation. Therefore, we showed that iron also caused dose-dependent ROS generation in K562 cells. The measurement of intracellular calcium was determined using Furo-2 with a fluorescence spectrophotometer. The iron delivery process to the cytoplasmic iron pool was examined by monitoring the fluorescence of cells loaded with calcein-acetoxymethyl. Our data showed that iron increased intracellular calcium, and this response was 8 times higher when cells were incubated with DFO. K562 cells with DFO caused a 3.5 times increase of intracellular calcium in the presence of doxorubicin (DOX). In conclusion, DFO induces intracellular calcium and increases their sensitivity to DOX, a chemotherapeutic agent. PMID:26773173

  20. Insights into the Structure and Metabolic Function of Microbes That Shape Pelagic Iron-Rich Aggregates ( Iron Snow )

    SciTech Connect

    Lu, S; Chourey, Karuna; REICHE, M; Nietzsche, S; Shah, Manesh B; Hettich, Robert {Bob} L; Kusel, K

    2013-01-01

    Metaproteomics combined with total nucleic acid-based methods aided in deciphering the roles of microorganisms in the formation and transformation of iron-rich macroscopic aggregates (iron snow) formed in the redoxcline of an acidic lignite mine lake. Iron snow had high total bacterial 16S rRNA gene copies, with 2 x 109 copies g (dry wt)-1 in the acidic (pH 3.5) central lake basin and 4 x 1010 copies g (dry wt)-1 in the less acidic (pH 5.5) northern lake basin. Active microbial communities in the central basin were dominated by Alphaproteobacteria (36.6%) and Actinobacteria (21.4%), and by Betaproteobacteria (36.2%) in the northern basin. Microbial Fe-cycling appeared to be the dominant metabolism in the schwertmannite-rich iron snow, because cloning and qPCR assigned up to 61% of active bacteria as Fe-cycling bacteria (FeB). Metaproteomics revealed 70 unique proteins from central basin iron snow and 283 unique proteins from 43 genera from northern basin. Protein identification provided a glimpse into in situ processes, such as primary production, motility, metabolism of acidophilic FeB, and survival strategies of neutrophilic FeB. Expression of carboxysome shell proteins and RubisCO indicated active CO2 fixation by Fe(II) oxidizers. Flagellar proteins from heterotrophs indicated their activity to reach and attach surfaces. Gas vesicle proteins related to CO2-fixing Chlorobium suggested that microbes could influence iron snow sinking. We suggest that iron snow formed by autotrophs in the redoxcline acts as a microbial parachute, since it is colonized by motile heterotrophs during sinking which start to dissolve schwertmannite.

  1. Neuroferritinopathy: a new inborn error of iron metabolism

    PubMed Central

    Keogh, Michael J.; Jonas, Patricia; Coulthard, Alan; Chinnery, Patrick F.; Burn, John

    2014-01-01

    Neuroferritinopathy is an autosomal dominant progressive movement disorder which occurs due to mutations in the ferritin light chain gene (FTL1). It presents in mid-adult life and is the only autosomal dominant disease in a group of conditions termed neurodegeneration with brain iron accumulation (NBIA). We performed brain MRI scans on 12 asymptomatic descendants of known mutation carriers. All three harbouring the pathogenic c.460InsA mutation showed iron deposition; these findings show pathological iron accumulation begins in early childhood which is of major importance in understanding and developing treatment for NBIA. PMID:22278127

  2. Divergent Responses of Coastal and Oceanic Synechococcus to Iron Limitation

    NASA Astrophysics Data System (ADS)

    Mackey, K. R.; McIlvin, M.; Post, A.; Saito, M. A.

    2014-12-01

    Marine Synechococcus are some of the most diverse and ubiquitous phytoplankton in the ocean, and are major contributors to global primary productivity. Iron (Fe) is a micronutrient required for maintenance of the photosynthetic apparatus that limits productivity in many parts of the ocean. To investigate how marine Synechococcus strains adapt and acclimate to Fe availability, we compared the growth, photophysiology, and protein abundance in two Synechococcus strains over a range of Fe concentrations. Synechococcus strain WH8102, from the permanently stratified southern Sargasso Sea in a region that receives significant dust deposition, had few acclimation strategies under low Fe and showed impaired growth rates and photophysiology as Fe declined. Coastal isolate WH8020, from the dynamic, seasonally variable North Atlantic Ocean, displayed a range of acclimation responses, including changes in Fe acquisition, storage, and photosynthetic electron transport proteins, substitution of flavodoxin for ferredoxin, and modified photophysiology. Each of these acclimation responses occurred at different Fe threshold concentrations over which growth rate remained remarkably stable. This study demonstrates that genomic streamlining in waters with low nitrogen and phosphorus may favor the loss of Fe acclimation genes when the Fe supply is consistent over time, and expands the regions where Fe stress is thought to occur to most coastal environments.

  3. Red blood cell and iron metabolism during space flight.

    PubMed

    Smith, Scott M

    2002-10-01

    Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood. PMID:12361780

  4. Red blood cell and iron metabolism during space flight

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.

    2002-01-01

    Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.

  5. [Effect of hepcidin on iron metabolism in athletes].

    PubMed

    Domínguez, Raúl; Garnacho-Castaño, Manuel Vicente; Maté-Muñoz, José Luis

    2014-01-01

    The role of iron in the human body is essential, and athletes must always try to keep an adequate iron status. Hepcidin is proposed as the main hormone responsible for the control of iron reserves in the body, given its ability to induce degradation of ferroportin. The action of hepcidin on ferroportin leads to a decreased dietary iron absorption, as well as to a decrease in macrophages. Several factors such as the iron status, the amount of dietary iron, the inflammation, the hypoxia, the testosterone and the physical exercise have been pointed out as affecting the synthesis of hepcidin. This study has aimed at analysing the researches on hepcidin response to exercise, as well as designing a specific strategy to prevent a potential ferropenic status in athletes. The main findings are an association between exercise at an intensity over 65% VO2max and transient increases in the synthesis of hepcidin, and a possible regulatory effect of intermittent hypoxic stimuli in the early post-exercise recovery. Other factors such as the training volume, sex, kind of exercise or the type of surface where the training takes place do not seem to affect the response of hepcidin to exercise. PMID:25433101

  6. Haemolysis and Perturbations in the Systemic Iron Metabolism of Suckling, Copper-Deficient Mosaic Mutant Mice – An Animal Model of Menkes Disease

    PubMed Central

    Lenartowicz, Małgorzata; Starzyński, Rafał R.; Krzeptowski, Wojciech; Grzmil, Paweł; Bednarz, Aleksandra; Ogórek, Mateusz; Pierzchała, Olga; Staroń, Robert; Gajowiak, Anna; Lipiński, Paweł

    2014-01-01

    The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1). This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb) from the circulation, as well as the induction of haem oxygenase 1 (HO1) in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism. PMID:25247420

  7. Lipocalin 2 alleviates iron toxicity by facilitating hypoferremia of inflammation and limiting catalytic iron generation.

    PubMed

    Xiao, Xia; Yeoh, Beng San; Saha, Piu; Olvera, Rodrigo Aguilera; Singh, Vishal; Vijay-Kumar, Matam

    2016-06-01

    Iron is an essential transition metal ion for virtually all aerobic organisms, yet its dysregulation (iron overload or anemia) is a harbinger of many pathologic conditions. Hence, iron homeostasis is tightly regulated to prevent the generation of catalytic iron (CI) which can damage cellular biomolecules. In this study, we investigated the role of iron-binding/trafficking innate immune protein, lipocalin 2 (Lcn2, aka siderocalin) on iron and CI homeostasis using Lcn2 knockout (KO) mice and their WT littermates. Administration of iron either systemically or via dietary intake strikingly upregulated Lcn2 in the serum, urine, feces, and liver of WT mice. However, similarly-treated Lcn2KO mice displayed elevated CI, augmented lipid peroxidation and other indices of organ damage markers, implicating that Lcn2 responses may be protective against iron-induced toxicity. Herein, we also show a negative association between serum Lcn2 and CI in the murine model of dextran sodium sulfate (DSS)-induced colitis. The inability of DSS-treated Lcn2KO mice to elicit hypoferremic response to acute colitis, implicates the involvement of Lcn2 in iron homeostasis during inflammation. Using bone marrow chimeras, we further show that Lcn2 derived from both immune and non-immune cells participates in CI regulation. Remarkably, exogenous rec-Lcn2 supplementation suppressed CI levels in Lcn2KO serum and urine. Collectively, our results suggest that Lcn2 may facilitate hypoferremia, suppress CI generation and prevent iron-mediated adverse effects. PMID:27007712

  8. Persistence of iron limitation in the western subarctic Pacific SEEDS II mesoscale fertilization experiment

    NASA Astrophysics Data System (ADS)

    Wells, Mark L.; Trick, Charles G.; Cochlan, William P.; Beall, Ben

    2009-12-01

    The cumulative evidence from more than a dozen mesoscale iron-enrichment studies in high nitrate low chlorophyll (HNLC) waters demonstrates that iron limitation is widespread and very likely affects atmospheric carbon dioxide and thus global climate. However, the responses of microphytoplankton (>20 μm), predominantly diatoms, vary greatly among these mesoscale experiments even though similar amounts of iron were added, making it difficult to quantitatively incorporate iron effects into global climate models. Nowhere is this difference more dramatic than between the massive bloom observed during Subarctic Pacific Iron Experiment for Ecosystem Dynamics Study (SEEDS) I and the order of magnitude smaller ecosystem response in SEEDS II; two mesocale experiments performed in the same HNLC region of the western subarctic Pacific in different years. Deckboard incubation experiments initiated during the early, middle, and late stages of the 32-day SEEDS II experiment show that while the two iron infusions increased phytoplankton growth, diatoms remained significantly limited by iron availability, despite total dissolved Fe concentrations in the patch being well above the diffusion-limited threshold for rapid diatom growth. This iron limitation was apparent <6 days after the initial iron infusion and was not alleviated by the second, smaller iron infusion. In contrast, smaller phytoplankton (<20 μm) showed a more restricted response to further iron amendments, indicating that their iron nutrition was near optimal. Iron complexed to desferrioximine B, a commonly available siderophore produced by at least one marine bacterium, was poorly available to diatoms throughout the patch evolution, indicating that these diatoms lacked the ability to induce high-affinity iron uptake systems. These results suggest that the strong organic complexation of Fe(III) observed in the SEEDS II-fertilized patch was not compatible with rapid diatom growth. In contrast, iron associated with

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

    PubMed Central

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem; O’Brien, Edward J.; Szubin, Richard; Palsson, Bernhard O.

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response to iron availability using genome-wide measurements (ChIP-exo and RNA-seq). Integrative data analysis reveals that a total of 81 genes in 42 transcription units are directly regulated by three different modes of Fur regulation, including apo- and holo-Fur activation and holo-Fur repression. We show that Fur connects iron transport and utilization enzymes with negative-feedback loop pairs for iron homeostasis. In addition, direct involvement of Fur in the regulation of DNA synthesis, energy metabolism, and biofilm development is found. These results show how Fur exhibits a comprehensive regulatory role affecting many fundamental cellular processes linked to iron metabolism in order to coordinate the overall response of E. coli to iron availability. PMID:25222563

  10. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress.

    PubMed

    Koskenkorva-Frank, Taija S; Weiss, Günter; Koppenol, Willem H; Burckhardt, Susanna

    2013-12-01

    Production of minute concentrations of superoxide (O2(*-)) and nitrogen monoxide (nitric oxide, NO*) plays important roles in several aspects of cellular signaling and metabolic regulation. However, in an inflammatory environment, the concentrations of these radicals can drastically increase and the antioxidant defenses may become overwhelmed. Thus, biological damage may occur owing to redox imbalance-a condition called oxidative and/or nitrosative stress. A complex interplay exists between iron metabolism, O2(*-), hydrogen peroxide (H2O2), and NO*. Iron is involved in both the formation and the scavenging of these species. Iron deficiency (anemia) (ID(A)) is associated with oxidative stress, but its role in the induction of nitrosative stress is largely unclear. Moreover, oral as well as intravenous (iv) iron preparations used for the treatment of ID(A) may also induce oxidative and/or nitrosative stress. Oral administration of ferrous salts may lead to high transferrin saturation levels and, thus, formation of non-transferrin-bound iron, a potentially toxic form of iron with a propensity to induce oxidative stress. One of the factors that determine the likelihood of oxidative and nitrosative stress induced upon administration of an iv iron complex is the amount of labile (or weakly-bound) iron present in the complex. Stable dextran-based iron complexes used for iv therapy, although they contain only negligible amounts of labile iron, can induce oxidative and/or nitrosative stress through so far unknown mechanisms. In this review, after summarizing the main features of iron metabolism and its complex interplay with O2(*-), H2O2, NO*, and other more reactive compounds derived from these species, the potential of various iron therapies to induce oxidative and nitrosative stress is discussed and possible underlying mechanisms are proposed. Understanding the mechanisms, by which various iron formulations may induce oxidative and nitrosative stress, will help us

  11. Metabolic response to subacute and subchronic iron overload in a rat model.

    PubMed

    Adham, Khadiga G; Farhood, Manal H; Daghestani, Maha H; Aleisa, Nadia A; Alkhalifa, Ahlam A; El Amin, Maha H; Virk, Promy; Al-Obeid, Mai A; Al-Humaidhi, Eman M H

    2015-12-01

    One of the common causes of iron overload is excessive iron intake in cases of iron-poor anemia, where iron saccharate complex (ISC) is routinely used to optimize erythropoiesis. However, non-standardized ISC administration could entail the risk of iron overload. To induce iron overload, Wistar rats were intraperitoneally injected with subacute (0.2 mg kg⁻¹) and subchronic (0.1 mg kg⁻¹) overdoses of ISC for 2 and 4 weeks, respectively. Iron status was displayed by an increase in transferrin saturation (up to 332%) and serum and liver iron burden (up to 19.3 μmol L⁻¹ and 13.2 μmol g⁻¹ wet tissue, respectively) together with a drop in total and unsaturated iron binding capacities "TIBC, UIBC" as surrogate markers of transferrin activity. Iron-induced leukocytosis (up to 140%), along with the decline in serum transferrin markers (up to 43%), respectively, mark positive and negative acute phase reactions. Chemical stress was demonstrated by a significant rise (p > 0.05) in indices of the hemogram (erythrocytes, hemoglobin, hematocrit, leukocytes) and stress metabolites [corticosterone (CORT) and lactate]. Yet, potential causes of the unexpected decline in serum activities of ALT, AST and LDH (p > 0.05) might include decreased hepatocellular enzyme production and/or inhibition or reduction of the enzyme activities. The current findings highlight the toxic role of elevated serum and liver iron in initiating erythropoiesis and acute phase reactions, modifying iron status and animal organ function, changing energy metabolism and bringing about accelerated glycolysis and impaired lactate clearance supposedly by decreasing anaerobic threshold and causing premature entering to the anaerobic system. PMID:26616369

  12. Iron metabolism and cell membranes. III. Iron-induced alterations in HeLa cells.

    PubMed Central

    Jauregui, H. O.; Bradford, W. D.; Arstila, A. U.; Kinney, T. D.; Trump, B. F.

    1975-01-01

    The morphologic characteristics of acute iron loading were studied in HeLa cells incubated in an iron-enriched Eagle's medium containing 500 mug/ml of iron. Chemical studies showed that ferritin synthesis was rapidly induced and the concentration of intracellular ferritin increased up to 72 hours. Closely coupled with an increase in HeLa cell ferritin was a marked decrease in the rate of cell multiplication. The significant ultrastructural findings of iron-induced HeLa cell injury are characterized by the appearance of both autophagic multivesicular and residual bodies over the first 72 hours of iron incubation. The prominence of multivesicular bodies was noted after only 4 hours' incubation, with iron and myelin figures first appearing after 6 hours. Thus, the partial arrest of cell multiplication was associated with an increase in cytoplasmic residual bodies containing iron and other debris. The distribution of intracellular ferritin within HeLa cells differs significantly from the distribution described previously in hepatic parenchymal cells. In HeLa cells, ferritin particles were confined to lysosomal vesicles and were not identified in cell sap, endoplasmic reticulum, or Golgi apparatus. Images Figure 8 Figure 1 Figure 9 Figure 10 Figure 11 Figure 12 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1155583

  13. Neisseria gonorrhoeae Modulates Iron-Limiting Innate Immune Defenses in Macrophages

    PubMed Central

    Zughaier, Susu M.; Kandler, Justin L.; Shafer, William M.

    2014-01-01

    Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. The gonococcus can survive extracellularly and intracellularly, but in both environments the bacteria must acquire iron from host proteins for survival. However, upon infection the host uses a defensive response by limiting the bioavailability of iron by a number of mechanisms including the enhanced expression of hepcidin, the master iron-regulating hormone, which reduces iron uptake from the gut and retains iron in macrophages. The host also secretes the antibacterial protein NGAL, which sequesters bacterial siderophores and therefore inhibits bacterial growth. To learn whether intracellular gonococci can subvert this defensive response, we examined expression of host genes that encode proteins involved in modulating levels of intracellular iron. We found that N. gonorrhoeae can survive in association (tightly adherent and intracellular) with monocytes and macrophages and upregulates a panel of its iron-responsive genes in this environment. We also found that gonococcal infection of human monocytes or murine macrophages resulted in the upregulation of hepcidin, NGAL, and NRAMP1 as well as downregulation of the expression of the gene encoding the short chain 3-hydroxybutyrate dehydrogenase (BDH2); BDH2 catalyzes the production of the mammalian siderophore 2,5-DHBA involved in chelating and detoxifying iron. Based on these findings, we propose that N. gonorrhoeae can subvert the iron-limiting innate immune defenses to facilitate iron acquisition and intracellular survival. PMID:24489950

  14. Insights into the pathophysiology of iron metabolism in Pythium insidiosum infections.

    PubMed

    Zanette, R A; Bitencourt, P E R; Alves, S H; Fighera, R A; Flores, M M; Wolkmer, P; Hecktheuer, P A; Thomas, L R; Pereira, P L; Loreto, E S; Santurio, J M

    2013-03-23

    Pythium insidiosum causes life-threatening disease in mammals. Animals with pythiosis usually develop anemia, and most human patients are reported to have thalassemia and the major consequence of thalassemia, iron overload. Therefore, this study evaluated the iron metabolism in rabbits experimentally infected with P. insidiosum. Ten infected rabbits were divided into two groups: one groups received a placebo, and the other was treated with immunotherapy. Five rabbits were used as negative controls. The hematological and biochemical parameters, including the iron profile, were evaluated. Microcytic hypochromic anemia was observed in the infected animals, and this condition was more accentuated in the untreated group. The serum iron level was decreased, whereas the transferrin level was increased, resulting in low saturation. The level of stainable iron in hepatocytes was markedly decreased in the untreated group. A high correlation was observed between the total iron binding capacity and the lesion size, and this correlation likely confirms the affinity of P. insidiosum for iron. The data from this study corroborate the previous implications of iron in the pathogenesis of pythiosis in humans and animals. PMID:23182911

  15. Effects of dietary carbohydrate on iron metabolism and cytochrome oxidase activity in copper-deficient rats

    SciTech Connect

    Johnson, M.A.; Henderson, J.

    1986-03-01

    The effects of dietary carbohydrate on the metabolism of iron and the activity of cytochrome oxidase were examined in Cu-deficient and Cu-adequate rats. Male rats (n = 36) were fed one of six diets which varied in copper level (Cu-: < 0.6 ppm or Cu+: 8.2 ppm) and carbohydrate type (cornstarch, sucrose or fructose). After 31 days, Cu- rats had 50% more iron in the liver and 38, 30 and 18% less iron in the tibia, spleen and kidneys, respectively, than Cu+ rats. The activity of cytochrome oxidase in the bone marrow, heart, and liver were 59%, 51%, and 43%, respectively, of the levels in Cu/sup +/ rats. The type of dietary carbohydrate significantly affected the development of anemia during copper deficiency. Cu-rats fed cornstarch, sucrose or fructose had hematocrit levels which were 92, 83 or 73%, respectively, of Cu+ rats. Similarly, the levels of iron in the tibias of Cu- rats fed cornstarch, sucrose or fructose were 69, 66 or 54%, respectively, of Cu+ rats. The hematocrit levels of Cu- rats were positively correlated to both tibia iron levels (r = 0.64, p < 0.005) and liver cytochrome oxidase activities (r = 0.50, p < 0.05). Thus, it appears that changes in the metabolism of iron may be involved with the development of anemia in Cu- rats fed fructose or sucrose.

  16. Effects of Iron Limitation on Photosystem II Composition and Light Utilization in Dunaliella tertiolecta.

    PubMed Central

    Vassiliev, I. R.; Kolber, Z.; Wyman, K. D.; Mauzerall, D.; Shukla, V. K.; Falkowski, P. G.

    1995-01-01

    The effects of iron limitation on photosystem II (PSII) composition and photochemical energy conversion efficiency were studied in the unicellular chlorophyte alga Dunaliella tertiolecta. The quantum yield of photochemistry in PSII, inferred from changes in variable fluorescence normalized to the maximum fluorescence yield, was markedly lower in iron-limited cells and increased 3-fold within 20 h following the addition of iron. The decrease in the quantum yield of photochemistry was correlated with increased fluorescence emission from the antenna. In iron-limited cells, flash intensity saturation profiles of variable fluorescence closely followed a cumulative one-hit Poisson model, suggesting that PSII reaction centers are energetically isolated, whereas in iron-replete cells, the slope of the profile was steeper and the calculated probability of energy transfer between reaction centers increased to >0.6. Immunoassays revealed that in iron-limited cells the reaction center proteins, D1, CP43, and CP47, were markedly reduced relative to the peripheral light-harvesting Chl-protein complex of PSII, whereas the [alpha] subunit of cytochrome b559 was about 10-fold higher. Spectroscopic analysis established that the cytochrome b559 peptide did not contain an associated functional heme. We conclude that the photochemical conversion of absorbed excitation energy in iron-limited cells is limited by the number of photochemical traps per unit antenna. PMID:12228645

  17. The effect of iron limitation on the transcriptome and proteome of Pseudomonas fluorescens Pf-5

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We investigated the transcriptomic and proteomic effects of iron limitation on Pf-5 by employing microarray and iTRAQ techniques, respectively. Analysis of this data revealed that molecular elements involved in iron homeostasis, including the pyoverdine and enantio-pyochelin biosynthesis clusters a...

  18. Iron Metabolism in Field Hockey Players During an Annual Training Cycle

    PubMed Central

    Podgórski, Tomasz; Kryściak, Jakub; Konarski, Jan; Domaszewska, Katarzyna; Durkalec-Michalski, Krzysztof; Strzelczyk, Ryszard; Pawlak, Maciej

    2015-01-01

    Post-physical training changes in iron metabolism in the human body often occur. To fully describe these processes, fifteen male Polish National Team field hockey players (age 27.7 ± 5.2 years, body mass 72.8 ± 7.6 kg and body height 177.1 ± 5.7 cm) were examined in three phases of an annual training cycle: preparatory (T1), competitive (T2) and transition (T3). To assess aerobic fitness, maximal oxygen uptake (VO2max) was evaluated. Based on the iron concentration, the changes in total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and other selected haematological indicators (haemoglobin, erythrocytes, mean corpuscular haemoglobin - MCH) in iron metabolism were estimated. The average values of maximum oxygen uptake increased from 54.97 ± 3.62 ml·kg−1·min−1 in T1 to 59.93 ± 3.55 ml·kg−1·min−1 in T2 (p<0.05) and then decreased to 56.21 ± 4.56 ml·kg−1·min−1 in T3 (p<0.05). No statistically significant changes in the erythrocyte count were noted. The MCH and haemoglobin concentration decreased between T1 and T2. The maximal exercise test caused a significant (p<0.05) increase in the plasma iron concentration during the competition and transition phases. Progressive but non-significant increases in resting iron concentration, TIBC and UIBC in the analysed annual training cycle were noted. To show global changes in iron metabolism in the human body, it is necessary to determine additional variables, i.e. UIBC, TIBC, haemoglobin, MCH or the erythrocyte count. The direction of changes in iron metabolism depends on both the duration and intensity of the physical activity and the fitness level of the subjects. Dietary intake of iron increases the level of this trace element and prevents anaemia associated with training overloads. PMID:26557195

  19. Response of the Unicellular Diazotrophic Cyanobacterium Crocosphaera watsonii to Iron Limitation

    PubMed Central

    Jacq, Violaine; Ridame, Céline; L'Helguen, Stéphane; Kaczmar, Fanny; Saliot, Alain

    2014-01-01

    Iron (Fe) is widely suspected as a key controlling factor of N2 fixation due to the high Fe content of nitrogenase and photosynthetic enzymes complex, and to its low concentrations in oceanic surface seawaters. The influence of Fe limitation on the recently discovered unicellular diazotrophic cyanobacteria (UCYN) is poorly understood despite their biogeochemical importance in the carbon and nitrogen cycles. To address this knowledge gap, we conducted culture experiments on Crocosphaera watsonii WH8501 growing under a range of dissolved Fe concentrations (from 3.3 to 403 nM). Overall, severe Fe limitation led to significant decreases in growth rate (2.6-fold), C, N and chlorophyll a contents per cell (up to 4.1-fold), N2 and CO2 fixation rates per cell (17- and 7-fold) as well as biovolume (2.2-fold). We highlighted a two phased response depending on the degree of limitation: (i) under a moderate Fe limitation, the biovolume of C. watsonii was strongly reduced, allowing the cells to keep sufficient energy to maintain an optimal growth, volume-normalized contents and N2 and CO2 fixation rates; (ii) with increasing Fe deprivation, biovolume remained unchanged but the entire cell metabolism was affected, as shown by a strong decrease in the growth rate, volume-normalized contents and N2 and CO2 fixation rates. The half-saturation constant for growth of C. watsonii with respect to Fe is twice as low as that of the filamentous Trichodesmium indicating a better adaptation of C. watsonii to poor Fe environments than filamentous diazotrophs. The physiological response of C. watsonii to Fe limitation was different from that previously shown on the UCYN Cyanothece sp, suggesting potential differences in Fe requirements and/or Fe acquisition within the UCYN community. These results contribute to a better understanding of how Fe bioavailability can control the activity of UCYN and explain the biogeography of diverse N2 fixers in ocean. PMID:24466221

  20. Using skin to assess iron accumulation in human metabolic disorders

    NASA Astrophysics Data System (ADS)

    Guinote, I.; Fleming, R.; Silva, R.; Filipe, P.; Silva, J. N.; Veríssimo, A.; Napoleão, P.; Alves, L. C.; Pinheiro, T.

    2006-08-01

    The distribution of Fe in skin was assessed to monitor body Fe status in human hereditary hemochromatosis. The paper reports on data from nine patients with hemochromatosis that were studied along the therapeutic programme. Systemic evaluation of Fe metabolism was carried out by measuring with PIXE technique the Fe concentration in plasma and blood cells, and by determining with biochemical methods the indicators of Fe transport in serum (ferritin and transferrin). The Fe distribution and concentration in skin was assessed by nuclear microscopy and Fe deposits in liver estimated through nuclear magnetic resonance. Elevated Fe concentrations in skin were related to increased plasma Fe (p < 0.004), serum ferritin content (p < 0.01) and Fe deposits in liver (p < 0.004). The relationship of Fe deposits in organs and metabolism markers may help to better understand Fe pools mobilisation and to establish the quality of skin as a marker for the disease progression and therapy efficacy.

  1. The role of iron in Mycobacterium smegmatis biofilm formation: the exochelin siderophore is essential in limiting iron conditions for biofilm formation but not for planktonic growth

    PubMed Central

    Ojha, Anil; Hatfull, Graham F

    2007-01-01

    Many species of mycobacteria form structured biofilm communities at liquid–air interfaces and on solid surfaces. Full development of Mycobacterium smegmatis biofilms requires addition of supplemental iron above 1 μM ferrous sulphate, although addition of iron is not needed for planktonic growth. Microarray analysis of the M. smegmatis transcriptome shows that iron-responsive genes – especially those involved in siderophore synthesis and iron uptake – are strongly induced during biofilm formation reflecting a response to iron deprivation, even when 2 μM iron is present. The acquisition of iron under these conditions is specifically dependent on the exochelin synthesis and uptake pathways, and the strong defect of an iron–exochelin uptake mutant suggests a regulatory role of iron in the transition to biofilm growth. In contrast, although the expression of mycobactin and iron ABC transport operons is highly upregulated during biofilm formation, mutants in these systems form normal biofilms in low-iron (2 μM) conditions. A close correlation between iron availability and matrix-associated fatty acids implies a possible metabolic role in the late stages of biofilm maturation, in addition to the early regulatory role. M. smegmatis surface motility is similarly dependent on iron availability, requiring both supplemental iron and the exochelin pathway to acquire it. PMID:17854402

  2. Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts.

    PubMed

    del Rey, Mónica; Benito, Rocío; Fontanillo, Celia; Campos-Laborie, Francisco J; Janusz, Kamila; Velasco-Hernández, Talía; Abáigar, María; Hernández, María; Cuello, Rebeca; Borrego, Daniel; Martín-Zanca, Dionisio; De Las Rivas, Javier; Mills, Ken I; Hernández-Rivas, Jesús M

    2015-01-01

    The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified. PMID:25955609

  3. Deregulation of Genes Related to Iron and Mitochondrial Metabolism in Refractory Anemia with Ring Sideroblasts

    PubMed Central

    del Rey, Mónica; Benito, Rocío; Fontanillo, Celia; Campos-Laborie, Francisco J.; Janusz, Kamila; Velasco-Hernández, Talía; Abáigar, María; Hernández, María; Cuello, Rebeca; Borrego, Daniel; Martín-Zanca, Dionisio; De Las Rivas, Javier; Mills, Ken I.; Hernández-Rivas, Jesús M.

    2015-01-01

    The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. A total of 231 low-risk MDS patients and 81 controls were studied. Gene expression analysis revealed that iron metabolism and mitochondrial function had the highest number of genes deregulated in RARS patients compared to controls and the refractory cytopenias with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37 and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant differences were observed between patients with SF3B1 mutations and patients without the mutations. The deregulation of genes involved in iron and mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New variants that could be involved in the pathogenesis of these diseases have been identified. PMID:25955609

  4. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    PubMed

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P < 0.05) as a consequence of lower iron levels. Ferritin and transferrin levels were higher in both phases (acute and subclinical) of the disease. The AOPP and FRAP levels increased in infected animals on the acute phase; however, the opposite occurred in the subclinical phase. We concluded that dogs naturally infected by E. canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology. PMID:26724737

  5. Modeling iron limitation of primary production in the coastal Gulf of Alaska

    NASA Astrophysics Data System (ADS)

    Fiechter, Jerome; Moore, Andrew M.; Edwards, Christopher A.; Bruland, Kenneth W.; Di Lorenzo, Emanuele; Lewis, Craig V. W.; Powell, Thomas M.; Curchitser, Enrique N.; Hedstrom, Kate

    2009-12-01

    A lower trophic level NPZD ecosystem model with explicit iron limitation on nutrient uptake is coupled to a three-dimensional coastal ocean circulation model to investigate the regional ecosystem dynamics of the northwestern coastal Gulf of Alaska (CGOA). Iron limitation is included in the NPZD model by adding governing equations for two micro-nutrient compartments: dissolved iron and phytoplankton-associated iron. The model has separate budgets for nitrate (the limiting macro-nutrient in the standard NPZD model) and for iron, with iron limitation on nitrate uptake being imposed as a function of the local phytoplankton realized Fe:C ratio. While the ecosystem model represents a simple approximation of the complex lower trophic level ecosystem of the northwestern CGOA, simulated chlorophyll concentrations reproduce the main characteristics of the spring bloom, high shelf primary production, and "high-nutrient, low-chlorophyll" (HNLC) environment offshore. Over the 1998-2004 period, model-data correlations based on spatially averaged, monthly mean chlorophyll concentrations are on average 0.7, with values as high as 0.9 and as low as 0.5 for individual years. The model also provides insight on the importance of micro- and macro-nutrient limitation on the shelf and offshore, with the shelfbreak region acting as a transition zone where both nitrate and iron availability significantly impact phytoplankton growth. Overall, the relative simplicity of the ecosystem model provides a useful platform to perform long-term simulations to investigate the seasonal and interannual CGOA ecosystem variability, as well as to conduct sensitivity studies to evaluate the robustness of simulated fields to ecosystem model parameterization and forcing. The ability of the model to differentiate between nitrate-limited, and iron-limited growth conditions, and to identify their spatial and temporal occurrences, is also a first step towards understanding the role of environmental gradients in

  6. Stoichiometry, Metabolism and Nutrient Limitation Across the Periodic Table in Natural Flowing-Water Chemostats

    NASA Astrophysics Data System (ADS)

    Cohen, M. J.; Nifong, R. L.; Kurz, M. J.; Cropper, W. P.; Martin, J. B.

    2014-12-01

    Relative supplies of macro and micronutrients (C,N,P, various metals), along with light and water, controls ecosystem metabolism, trophic energy transfer and community structure. Here we test the hypothesis, using measurements from 41 spring-fed rivers in Florida, that tissue stoichiometry indicates autotroph nutrient limitation status. Low variation in discharge, temperature and chemical composition within springs, but large variation across springs creates an ideal setting to assess the relationship between limitation and resource supply. Molar N:P ranges from 0.4 to 90, subjecting autotrophs to dramatically different nutrient supply. Over this gradient, species-specific autotroph tissue C:N:P ratios are strictly homeostatic, and with no evidence that nutrient supply affects species composition. Expanding to include 19 metals and micronutrients revealed autotrophs are more plastic in response to micronutrient variation, particularly for iron and manganese whose supply fluxes are small compared to biotic demand. Using a Droop model modified to reflect springs conditions (benthic production, light limitation, high hydraulic turnover), we show that tissue stoichiometry transitions from homeostatic to plastic with the onset of nutrient limitation, providing a potentially powerful new tool for predicting nutrient limitation and thus eutrophication in flowing waters.

  7. MYB10 and MYB72 are required for growth under iron-limiting conditions.

    PubMed

    Palmer, Christine M; Hindt, Maria N; Schmidt, Holger; Clemens, Stephan; Guerinot, Mary Lou

    2013-11-01

    Iron is essential for photosynthesis and is often a limiting nutrient for plant productivity. Plants respond to conditions of iron deficiency by increasing transcript abundance of key genes involved in iron homeostasis, but only a few regulators of these genes have been identified. Using genome-wide expression analysis, we searched for transcription factors that are induced within 24 hours after transferring plants to iron-deficient growth conditions. Out of nearly 100 transcription factors shown to be up-regulated, we identified MYB10 and MYB72 as the most highly induced transcription factors. Here, we show that MYB10 and MYB72 are functionally redundant and are required for plant survival in alkaline soil where iron availability is greatly restricted. myb10myb72 double mutants fail to induce transcript accumulation of the nicotianamine synthase gene NAS4. Both myb10myb72 mutants and nas4-1 mutants have reduced iron concentrations, chlorophyll levels, and shoot mass under iron-limiting conditions, indicating that these genes are essential for proper plant growth. The double myb10myb72 mutant also showed nickel and zinc sensitivity, similar to the nas4 mutant. Ectopic expression of NAS4 rescues myb10myb72 plants, suggesting that loss of NAS4 is the primary defect in these plants and emphasizes the importance of nicotianamine, an iron chelator, in iron homeostasis. Overall, our results provide evidence that MYB10 and MYB72 act early in the iron-deficiency regulatory cascade to drive gene expression of NAS4 and are essential for plant survival under iron deficiency. PMID:24278034

  8. DNA cleavage during ethanol metabolism: Role of superoxide radicals and catalytic iron

    SciTech Connect

    Rajasinghe, H.; Jayatilleke, E.; Shaw, S. )

    1990-01-01

    The generation of superoxide and related free radicals and the mobilization of catalytic iron due to ethanol metabolism have been suggested as mechanisms of alcohol-induced liver injury as well as of the increased risk of cancer observed in alcoholics. Cleavage of double stranded DNA is produced by both free radicals as well as by catalytic iron. The effects of ethanol metabolism on DNA cleavage were therefore studied in vitro as well as in vivo in isolated hepatocytes. Intactness of double stranded DNA was studied by measuring ethidium bromide fluorescence after DNA electrophoresis. In vitro, the metabolism of acetaldehyde by aldehyde oxidase caused cleavage of lambda phage DNA. Cleavage was inhibited by both superoxide dismutase and desferrioxamine indicating the role of superoxide radicals and catalytic iron respectively. Studies with HIND III digests of the lambda phage indicate a lack of specificity in the breaks with respect to nucleotide sequences. Addition of EDTA greatly enhanced cleavage. In vivo, ethanol metabolism caused minimal breakage in hepatocyte DNA and addition of acetaldehyde markedly enhanced cleavage; all cleavage was inhibited by desferrioxamine.

  9. Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

    PubMed Central

    Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

    2015-01-01

    Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

  10. Insights into the iron and sulfur energetic metabolism of Acidithiobacillus ferrooxidans by microarray transcriptome profiling

    SciTech Connect

    R. Quatrini; C. Appia-Ayme; Y. Denis; J. Ratouchniak; F. Veloso; J. Valdes; C. Lefimil; S. Silver; F. Roberto; O. Orellana; F. Denizot; E. Jedlicki; D. Holmes; V. Bonnefoy

    2006-09-01

    Acidithiobacillus ferrooxidans is a well known acidophilic, chemolithoautotrophic, Gram negative, bacterium involved in bioleaching and acid mine drainage. In aerobic conditions, it gains energy mainly from the oxidation of ferrous iron and/or reduced sulfur compounds present in ores. After initial oxidation of the substrate, electrons from ferrous iron or sulfur enter respiratory chains and are transported through several redox proteins to oxygen. However, the oxidation of ferrous iron and reduced sulfur compounds has also to provide electrons for the reduction of NAD(P) that is subsequently required for many metabolic processes including CO2 fixation. To help to unravel the enzymatic pathways and the electron transfer chains involved in these processes, a genome-wide microarray transcript profiling analysis was carried out. Oligonucleotides corresponding to approximately 3000 genes of the A. ferrooxidans type strain ATCC23270 were spotted onto glass-slides and hybridized with cDNA retrotranscribed from RNA extracted from ferrous iron and sulfur grown cells. The genes which are preferentially transcribed in ferrous iron conditions and those preferentially transcribed in sulfur conditions were analyzed. The expression of a substantial number of these genes has been validated by real-time PCR, Northern blot hybridization and/or immunodetection analysis. Our results support and extend certain models of iron and sulfur oxidation and highlight previous observations regarding the possible presence of alternate electron pathways. Our findings also suggest ways in which iron and sulfur oxidation may be co-ordinately regulated. An accompanying paper (Appia-Ayme et al.) describes results pertaining to other metabolic functions.

  11. Effect of Nordic Walking training on iron metabolism in elderly women

    PubMed Central

    Kortas, Jakub; Prusik, Katarzyna; Flis, Damian; Prusik, Krzysztof; Ziemann, Ewa; Leaver, Neil; Antosiewicz, Jedrzej

    2015-01-01

    Background Despite several, well-documented pro-healthy effects of regular physical training, its influence on body iron stores in elderly people remains unknown. At the same time, body iron accumulation is associated with high risk of different morbidities. Purpose We hypothesized that Nordic Walking training would result in pro-healthy changes in an elderly group of subjects by reducing body iron stores via shifts in iron metabolism-regulating proteins. Methods Thirty-seven women aged 67.7±5.3 years participated in this study. They underwent 32 weeks of training, 1-hour sessions three times a week, between October 2012 and May 2013. Fitness level, blood morphology, CRP, vitamin D, ferritin, hepcidin, and soluble Hjv were assessed before and after the training. Results The training program caused a significant decrease in ferritin, which serves as a good marker of body iron stores. Simultaneously, the physical cardiorespiratory fitness had improved. Furthermore, blood hepcidin was positively correlated with the ferritin concentration after the training. The concentration of blood CRP dropped, but the change was nonsignificant. The applied training resulted in a blood Hjv increase, which was inversely correlated with the vitamin D concentration. Conclusion Overall the Nordic Walking training applied in elderly people significantly reduced blood ferritin concentration, which explains the observed decrease in body iron stores. PMID:26664101

  12. Effects of long-distance running on iron metabolism and hematological parameters.

    PubMed

    Seiler, D; Nagel, D; Franz, H; Hellstern, P; Leitzmann, C; Jung, K

    1989-10-01

    In 110 well-trained participants of a 1000-km running competition lasting for 20 days hematological parameters, iron metabolism, and their respective changes during the race were investigated. Thirty-nine men and 11 women were accustomed to wholesome vegetarian food (lacto-ovovegetarian), 52 men and 8 women consumed a conventional western diet. In each group 50% of the runners finished the race. Before the competition started red blood cell count, hematocrit, and hemoglobin were on average below the values observed in the normal population in all groups. Both male and female runners consuming the wholesome diet showed significantly lower ferritin values than those on a western diet. During the first days of the competition hemolysis occurred leading to increased serum concentrations of bilirubin and iron and decreased haptoglobin levels. Hb concentrations showed a constant decrease during the race. Serum ferritin concentration rose about twofold within the first days and then decreased again without reaching pre-race levels. Serum iron concentrations showed a significant decrease between days 3 and 6. Iron loss was caused by hematuria (25% of all urines tested), gastrointestinal blood loss (10% of all stool specimens tested), and by sweating (4.5 micrograms iron/dl sweat). Our results suggest that especially in female long-distance runners it may be difficult to supply sufficient quantities of iron with the diet. PMID:2599724

  13. Phosphate and iron limitation of phytoplankton biomass in Lake Tahoe

    USGS Publications Warehouse

    Chang, Cecily C.Y.; Kuwabara, J.S.; Pasilis, S.P.

    1992-01-01

    Bioassays were carried out to assess the response of inoculated, single-species diatom populations (Cyclotella meneghiniana and Aulocosiera italica) to additions of synthetic chelators and phosphate. A chemical speciation model along with the field data was also used to predict how trace metal speciation, and hence bioavailability, was affected by the chelator additions. Results suggest that phosphate was limiting to phytoplankton biomass. Other solutes, Fe in particular, may also exert controls on biomass. Nitrate limitation seems less likely, although Fe-limiting conditions may have led to an effective N limitation because algae require Fe to carry out nitrate reduction. -from Authors

  14. Cytochromes and iron sulfur proteins in sulfur metabolism of phototrophic bacteria

    NASA Technical Reports Server (NTRS)

    Fischer, U.

    1985-01-01

    Dissimilatory sulfur metabolism in phototrophic sulfur bacteria provides the bacteria with electrons for photosynthetic electron transport chain and, with energy. Assimilatory sulfate reduction is necessary for the biosynthesis of sulfur-containing cell components. Sulfide, thiosulfate, and elemental sulfur are the sulfur compounds most commonly used by phototrophic bacteria as electron donors for anoxygenic photosynthesis. Cytochromes or other electron transfer proteins, like high-potential-iron-sulfur protein (HIPIP) function as electron acceptors or donors for most enzymatic steps during the oxidation pathways of sulfide or thiosulfate. Yet, heme- or siroheme-containing proteins themselves undergo enzymatic activities in sulfur metabolism. Sirohemes comprise a porphyrin-like prosthetic group of sulfate reductase. eenzymatic reactions involve electron transfer. Electron donors or acceptors are necessary for each reaction. Cytochromes and iron sulfur problems, are able to transfer electrons.

  15. Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila.

    PubMed

    O'Connor, Tamara J; Zheng, Huaixin; VanRheenen, Susan M; Ghosh, Soma; Cianciotto, Nicholas P; Isberg, Ralph R

    2016-08-01

    Legionella pneumophila is an intracellular bacterial pathogen that replicates in alveolar macrophages, causing a severe form of pneumonia. Intracellular growth of the bacterium depends on its ability to sequester iron from the host cell. In the L. pneumophila strain 130b, one mechanism used to acquire this essential nutrient is the siderophore legiobactin. Iron-bound legiobactin is imported by the transport protein LbtU. Here, we describe the role of LbtP, a paralog of LbtU, in iron acquisition in the L. pneumophila strain Philadelphia-1. Similar to LbtU, LbtP is a siderophore transport protein and is required for robust growth under iron-limiting conditions. Despite their similar functions, however, LbtU and LbtP do not contribute equally to iron acquisition. The Philadelphia-1 strain lacking LbtP is more sensitive to iron deprivation in vitro Moreover, LbtP is important for L. pneumophila growth within macrophages while LbtU is dispensable. These results demonstrate that LbtP plays a dominant role over LbtU in iron acquisition. In contrast, loss of both LbtP and LbtU does not impair L. pneumophila growth in the amoebal host Acanthamoeba castellanii, demonstrating a host-specific requirement for the activities of these two transporters in iron acquisition. The growth defect of the ΔlbtP mutant in macrophages is not due to alterations in growth kinetics. Instead, the absence of LbtP limits L. pneumophila replication and causes bacteria to prematurely exit the host cell. These results demonstrate the existence of a preprogrammed exit strategy in response to iron limitation that allows L. pneumophila to abandon the host cell when nutrients are exhausted. PMID:27185787

  16. Vitamin D, Iron Metabolism, and Diet in Alpinists During a 2-Week High-Altitude Climb.

    PubMed

    Kasprzak, Zbigniew; Śliwicka, Ewa; Hennig, Karol; Pilaczyńska-Szcześniak, Łucja; Huta-Osiecka, Anna; Nowak, Alicja

    2015-09-01

    A defensive mechanism against hypobaric hypoxia at high altitude is erythropoesis. Some authors point to the contribution of vitamin D to the regulation of this process. The aim of the present study was to assess the 25-hydroxycholecalciferol (25(OH)D) level and its associations with iron metabolic and inflammatory indices in participants of a 2-week mountaineering expedition. The study sample included 9 alpinists practicing recreational mountain climbing. Every 2 or 3 days they set up a different base between 3200 and 3616 m with the intention of climbing 4000 m peaks in the Mont Blanc massif. Before their departure for the mountains and 2 days after returning to the sea level anthropometric parameters, hematological parameters, serum levels of 25(OH)D and iron metabolic indices were measured in all the participants. The composition of the participants' diet was also evaluated. The comparative analysis showed a significant decrease in body mass, BMI values, total iron, and 25(OH)D concentrations (p<0.05). Also significant increases in unsaturated iron-binding capacity, hematocrit, and C-reactive protein concentrations (p<0.05) were found. It can be concluded that the 2-week climbing expedition contributed to the reduction of 25(OH)D levels and these changes were associated with modulation of immune processes. Moreover, the climbers' diet requires some serious modifications. PMID:26125641

  17. Leu1 plays a role in iron metabolism and is required for virulence in Cryptococcus neoformans

    PubMed Central

    Do, Eunsoo; Hu, Guanggan; Caza, Mélissa; Oliveira, Debora; Kronstad, James W.; Jung, Won Hee

    2015-01-01

    Amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. Leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. Isopropylmalate dehydrogenase (Leu1) is an Fe-S cluster protein that is required for leucine biosynthesis in the model fungus Saccharomyces cerevisiae. The human pathogenic fungus Cryptococcus neoformans possesses an ortholog of S. cerevisiae Leu1, and our previous transcriptome data showed that the expression of LEU1 is regulated by iron availability. In this study, we characterized the role of Leu1 in iron homeostasis and the virulence of C. neoformans. We found that deletion of LEU1 caused leucine auxotrophy and that Leu1 may play a role in the mitochondrial-cytoplasmic Fe-S cluster balance. Whereas cytoplasmic Fe-S protein levels were not affected, mitochondrial Fe-S proteins were up- regulated in the leu1 mutant, suggesting that Leu1 mainly influences mitochondrial iron metabolism. The leu1 mutant also displayed increased sensitivity to oxidative stress and cell wall/membrane disrupting agents, which may have been caused by mitochondrial dysfunction. Furthermore, the leu1 mutant was deficient in capsule formation and showed attenuated virulence in a mouse inhalation model of cryptococcosis. Overall, our results indicate that Leu1 plays a role in iron metabolism and is required for virulence in C. neoformans. PMID:25554701

  18. Zebrafish in the sea of mineral (iron, zinc, and copper) metabolism

    PubMed Central

    Zhao, Lu; Xia, Zhidan; Wang, Fudi

    2014-01-01

    Iron, copper, zinc, and eight other minerals are classified as essential trace elements because they present in minute in vivo quantities and are essential for life. Because either excess or insufficient levels of trace elements can be detrimental to life (causing human diseases such as iron-deficiency anemia, hemochromatosis, Menkes syndrome and Wilson's disease), the endogenous levels of trace minerals must be tightly regulated. Many studies have demonstrated the existence of systems that maintain trace element homeostasis, and these systems are highly conserved in multiple species ranging from yeast to mice. As a model for studying trace mineral metabolism, the zebrafish is indispensable to researchers. Several large-scale mutagenesis screens have been performed in zebrafish, and these screens led to the identification of a series of metal transporters and the generation of several mutagenesis lines, providing an in-depth functional analysis at the system level. Moreover, because of their developmental advantages, zebrafish have also been used in mineral metabolism-related chemical screens and toxicology studies. Here, we systematically review the major findings of trace element homeostasis studies using the zebrafish model, with a focus on iron, zinc, copper, selenium, manganese, and iodine. We also provide a homology analysis of trace mineral transporters in fish, mice and humans. Finally, we discuss the evidence that zebrafish is an ideal experimental tool for uncovering novel mechanisms of trace mineral metabolism and for improving approaches to treat mineral imbalance-related diseases. PMID:24639652

  19. A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv⁻/⁻ mice.

    PubMed

    Padda, Ranjit Singh; Gkouvatsos, Konstantinos; Guido, Maria; Mui, Jeannie; Vali, Hojatollah; Pantopoulos, Kostas

    2015-02-15

    Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv(-/-) mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv(-/-) mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv(-/-) mice. Notably, steatosis was attenuated in Hjv(-/-) mice on the HFD+Fe regimen. Hjv(-/-) animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice. PMID:25501544

  20. Seasonally dependent iron limitation of nitrogen fixation in tropical forests of karst landscapes

    NASA Astrophysics Data System (ADS)

    Winbourne, J. B.; Brewer, S.; Houlton, B. Z.

    2015-12-01

    Limestone tropical forests in karst topography are one of the most poorly studied ecosystems on Earth, and has been substantially cleared by human activities throughout much of Central America. This ecosystem is noted for its high level of plant productivity, biomass, endemism and biological diversity compared to nearby neighboring tropical forests on volcanic rock substrates (Brewer et al. 2002). A question remains as to how limestone tropical forests are able to maintain the high nutrient demands of plant photosynthesis and tree biomass growth. Here, we demonstrate that rates of nitrogen (N) fixation are higher in limestone versus volcanic soil substrates, with direct evidence for the emergence of seasonally dependent iron limitation of N fixation in limestone tropical forest. N fixation rates showed a three-fold increase in response to iron additions, especially during the wet season when N demands of the forest trees are highest. In contrast, adjacent forests growing on the more classical acidic volcanic soils showed no response to iron or other nutrient additions. Biologically available pools of iron were exceedingly low in the limestone forest site, consistent with the complexation of iron under high pH conditions. Biological acquisition of iron, as measured by the concentration of iron chelating compounds (i.e. siderophores), provided additional evidence for iron limitation of microbial processes in limestone tropical forests, where concentrations were six times higher than those at the volcanic site. Our results suggest that the functioning of limestone tropical forest is strongly regulated by interactions between iron, soil pH, and N cycling.

  1. The phytopathogen Pseudomonas syringae pv. tomato DC3000 has three high-affinity iron-scavenging systems functional under iron limitation conditions but dispensable for pathogenesis.

    PubMed

    Jones, Alexander M; Wildermuth, Mary C

    2011-06-01

    High-affinity iron scavenging through the use of siderophores is a well-established virulence determinant in mammalian pathogenesis. However, few examples have been reported for plant pathogens. Here, we use a genetic approach to investigate the role of siderophores in Pseudomonas syringae pv. tomato DC3000 (DC3000) virulence in tomato. DC3000, an agronomically important pathogen, has two known siderophores for high-affinity iron scavenging, yersiniabactin and pyoverdin, and we uncover a third siderophore, citrate, required for growth when iron is limiting. Though growth of a DC3000 triple mutant unable to either synthesize or import these siderophores is severely restricted in iron-limited culture, it is fully pathogenic. One explanation for this phenotype is that the DC3000 triple mutant is able to directly pirate plant iron compounds such as heme/hemin or iron-nicotianamine, and our data indicate that DC3000 can import iron-nicotianamine with high affinity. However, an alternative explanation, supported by data from others, is that the pathogenic environment of DC3000 (i.e., leaf apoplast) is not iron limited but is iron replete, with available iron of >1 μM. Growth of the triple mutant in culture is restored to wild-type levels by supplementation with a variety of iron chelates at >1 μM, including iron(III) dicitrate, a dominant chelate of the leaf apoplast. This suggests that lower-affinity iron import would be sufficient for DC3000 iron nutrition in planta and is in sharp contrast to the high-affinity iron-scavenging mechanisms required in mammalian pathogenesis. PMID:21441525

  2. Iron metabolism in hamsters experimentally infected with Leptospira interrogans serovar Pomona: influence on disease pathogenesis.

    PubMed

    Sobroza, Ânderson O; Tonin, Alexandre A; Da Silva, Alekandro S; Dornelles, Guilherme L; Wolkmer, Patrícia; Duarte, Marta M M F; Hausen, Bruna S; Sangoi, Manuela B; Moresco, Rafael N; Stefani, Lenita M; Mazzantti, Cinthia M; Lopes, Sonia T A; Leal, Marta L R

    2014-12-01

    The aim of this study was to analyze the classic iron markers associated to the storage process in hamsters experimentally infected by Leptospira interrogans serovar Pomona. Four groups with six hamsters each were used; two were negative controls (C7 and C14) and two were composed by infected animals (T7 and T14). Blood samples were collected on the seventh (C7 and T7) and fourteenth days (C14 and T14) post-inoculation. Iron availability was determined in sera samples through the assessment of iron, ferritin, transferrin, and iron binding capacity, whereas the bone marrow was also evaluated for the presence of iron by Pearl's reaction. Additionally, the total antioxidant capacity (TAC) and total oxidant status (TOS) were assessed, along with hepcidin and IL-6 levels. Based on the results, it was possible to observe the onset of an anemic profile, predominantly hemolytic and regenerative. Also, The other parameters showed an increase in seric iron (P<0.01) and ferritin (P<0.01), and a positive Pearl's reaction in T7 and T14, when compared with the control groups. Transferrin levels decreased (P<0.05) in animals of T14 with saturation index. TAC was increased in both periods (P<0.01), while TOS was increased only on T14 (P<0.05). Hepcidin and IL-6 were increased on T7 and T14 (P<0.01). Therefore, it was observed that the serum profile from infected animals showed a strong hemolytic pattern, with some demonstration of ferric tissue sequestration when the infection tended to become chronic. The results show that iron metabolism is activated in hamsters infected by L. interrogans serovar Pomona. PMID:25449998

  3. Herbicide safeners: uses, limitations, metabolism, and mechanisms of action.

    PubMed

    Abu-Qare, Aqel W; Duncan, Harry J

    2002-09-01

    Several methods were examined to minimize crops injury caused by herbicides. Thus increase their selectivity. A selective herbicide is one that controls weeds at rates that do not injure the crop. Herbicides are selective in a particular crop within certain limits imposed by the herbicide, the plant, the application rate, the method and time of application, and environment conditions. Herbicide safeners are compounds of diverse chemical families. They are applied with herbicides to protect crops against their injury. Using chemical safeners offer practical, efficient and simple method of improving herbicide selectivity. This method has been applied successfully in cereal crops such as maize, rice and sorghum, against pre-emergence thiocarbamate and chloroacetanilide herbicides. Some reports indicate promising results for the development of safeners for post-emergence herbicides in broadleaved crops. Various hypotheses were proposed explaining mechanisms of action of herbicide safeners: interference with uptake and translocation of the herbicide, alteration in herbicide metabolism, and competition at site of action of the herbicide. Even though progress was made in the development of herbicide safeners and in understanding their mechanisms of action, more research is needed to elucidate clearly how these chemicals act and why their activity is restricted to particular crops and herbicides. PMID:12222792

  4. Springs as Model Systems for Aquatic Ecosystems Ecology: Stoichiometry, Metabolism and Nutrient Limitation

    NASA Astrophysics Data System (ADS)

    Cohen, M. J.; Nifong, R. L.; Kurz, M. J.; Martin, J. B.; Cropper, W. P.; Korhnak, L. V.

    2013-12-01

    Springs have been called nature's chemostats, where low variation in discharge, temperature and chemistry creates a natural laboratory in which to address basic questions about aquatic ecosystems. Ecological stoichiometry posits that patterns of metabolism, trophic energy transfer and community structure arise in response to coupled elemental cycles. In this work we synthesize several recent studies in Florida's iconic springs to explore the overarching hypothesis that stoichiometry can be used to indicate the nutrient limitation status of autotrophs and ecosystem metabolism. Of foremost importance is that the chemically stable conditions observed in springs ensures that autotroph tissue elemental composition, which is thought to vary with environmental supply, is near steady state. Moreover, the elemental ratios of discharging water vary dramatically across our study springs (for example, molar N:P ranges from 0.4:1 to 400:1), subjecting the communities of autotrophs, which are largely conserved across systems, to dramatically different nutrient supply. At the scale of whole ecosystem metabolism, we show that C:N:P ratios are strongly conserved across a wide gradient of environmental supplies, counter to the prediction of stoichiometric plasticity. Moreover, the absence of a relationship between gross primary production and nutrient concentrations or stoichiometry suggests that metabolic homeostasis may be a diagnostic symptom of nutrient saturation. At the scale of individual autotrophs, both submerged vascular plants and filamentous algae, this finding is strongly reinforced, with remarkable within-species tissue C:N:P homeostasis over large gradients, and no statistically significant evidence that gradients in nutrient supply affect autotroph composition. Expanding the suite of elements for which contemporaneous environment and tissue measurements are available to include 19 metals and micronutrients revealed that, while plants were homeostatic across large N

  5. Mechanisms of increased Trichodesmium fitness under iron and phosphorus co-limitation in the present and future ocean.

    PubMed

    Walworth, Nathan G; Fu, Fei-Xue; Webb, Eric A; Saito, Mak A; Moran, Dawn; Mcllvin, Matthew R; Lee, Michael D; Hutchins, David A

    2016-01-01

    Nitrogen fixation by cyanobacteria supplies critical bioavailable nitrogen to marine ecosystems worldwide; however, field and lab data have demonstrated it to be limited by iron, phosphorus and/or CO2. To address unknown future interactions among these factors, we grew the nitrogen-fixing cyanobacterium Trichodesmium for 1 year under Fe/P co-limitation following 7 years of both low and high CO2 selection. Fe/P co-limited cell lines demonstrated a complex cellular response including increased growth rates, broad proteome restructuring and cell size reductions relative to steady-state growth limited by either Fe or P alone. Fe/P co-limitation increased abundance of a protein containing a conserved domain previously implicated in cell size regulation, suggesting a similar role in Trichodesmium. Increased CO2 further induced nutrient-limited proteome shifts in widespread core metabolisms. Our results thus suggest that N2-fixing microbes may be significantly impacted by interactions between elevated CO2 and nutrient limitation, with broad implications for global biogeochemical cycles in the future ocean. PMID:27346420

  6. Mechanisms of increased Trichodesmium fitness under iron and phosphorus co-limitation in the present and future ocean

    PubMed Central

    Walworth, Nathan G.; Fu, Fei-Xue; Webb, Eric A.; Saito, Mak A.; Moran, Dawn; Mcllvin, Matthew R.; Lee, Michael D.; Hutchins, David A.

    2016-01-01

    Nitrogen fixation by cyanobacteria supplies critical bioavailable nitrogen to marine ecosystems worldwide; however, field and lab data have demonstrated it to be limited by iron, phosphorus and/or CO2. To address unknown future interactions among these factors, we grew the nitrogen-fixing cyanobacterium Trichodesmium for 1 year under Fe/P co-limitation following 7 years of both low and high CO2 selection. Fe/P co-limited cell lines demonstrated a complex cellular response including increased growth rates, broad proteome restructuring and cell size reductions relative to steady-state growth limited by either Fe or P alone. Fe/P co-limitation increased abundance of a protein containing a conserved domain previously implicated in cell size regulation, suggesting a similar role in Trichodesmium. Increased CO2 further induced nutrient-limited proteome shifts in widespread core metabolisms. Our results thus suggest that N2-fixing microbes may be significantly impacted by interactions between elevated CO2 and nutrient limitation, with broad implications for global biogeochemical cycles in the future ocean. PMID:27346420

  7. A comparison of iron extraction methods for the determination of degree of pyritisation and the recognition of iron-limited pyrite formation

    NASA Technical Reports Server (NTRS)

    Raiswell, R.; Canfield, D. E.; Berner, R. A.

    1994-01-01

    Measurements of degree of pyritisation require an estimate of sediment iron which is capable of reaction with dissolved sulphide to form pyrite, either directly or indirectly via iron monosulphide precursors. Three dissolution techniques (buffered dithionite, cold 1 M HCl, boiling 12 M HCl) were examined for their capacity to extract iron from a variety of iron minerals, and iron-bearing sediments, as a function of different extraction times and different grain sizes. All the iron oxides studied are quantitatively extracted by dithionite and boiling HCl (but not by cold HCl). Both HCl techniques extract more iron from silicates than does dithionite but probably about the same amounts as are potentially capable of sulphidation. Modern sediment studies indicate that most sedimentary pyrite is formed rapidly from iron oxides, with smaller amounts formed more slowly from iron silicates (if sufficient geologic time is available). It is therefore recommended that the degree of pyritisation be defined with respect to the dithionite-extractable (mainly iron oxide) pool and/or the boiling HCl-extractable pool (which includes some silicate iron) for the recognition of iron-limited pyritisation.

  8. Iron

    MedlinePlus

    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 ...

  9. Effects of dietary manganese and iron on manganese and iron metabolism during infancy

    SciTech Connect

    Kiehl, H.; Loennerdal, B. )

    1991-03-15

    To derive a better understanding of the metabolism of Mn during infancy, infant formulas with different levels of Mn and Fe were labeled with {sup 54}Mn and {sup 59}Fe and administered orally to suckling rats: control low-Fe formula; control with 100-times Mn; and control with 100-times Fe. Another group received 200 {mu}g MnCl{sub 2} daily during infancy. 12 hr post-dosing, the pattern of {sup 54}Mn distribution in the tissues paralleled that of {sup 59}Fe. An excess of either mineral decreased overall retention but led to higher recoveries of both elements in the proximal intestine and liver. Conversely, these recoveries in pups given Mn from birth were lower than in controls. Analysis of the cytosolic fractions from intestine and liver using FPLC gel filtration demonstrated the impact of the mineral loads on protein profiles. In all cases except the high-Mn dose, dietary manipulations resulted in greater relative levels of a high molecular weight protein with MW similar to ferritin. The high-Mn formula seemed to induce in the hepatocyte a lower MW protein with which most of the {sup 54}Mn and {sup 59}Fe was associated. These results suggest a possible role of Mn as a regulator in the synthesis of cytosolic proteins of the enterocyte and hepatocyte in infants.

  10. Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

    PubMed Central

    Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

    2014-01-01

    Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

  11. Metabolic Strategies in Energy-Limited Microbial Communities in the Anoxic Subsurface (Frasassi Cave System, Italy)

    NASA Astrophysics Data System (ADS)

    McCauley, R. L.; Jones, D. S.; Schaperdoth, I.; Steinberg, L.; Macalady, J. L.

    2010-12-01

    Two major sources of energy, light and chemical potential, are available to microorganisms. However, energy is not always abundant and is often a limiting factor in microbial survival and replication. The anoxic, terrestrial subsurface offers a unique opportunity to study microorganisms and their potentially novel metabolic strategies that are relevant for understanding biogeochemistry and biosignatures as related to the non-photosynthetic, energy-limited environments on the modern and ancient Earth and elsewhere in the solar system. Geochemical data collected in a remote stratified lake 600 m below ground surface in the sulfidic Frasassi cave system (Italy) suggest that little redox energy is available for life, consistent with low signal from domain-specific FISH probes. The carbon isotope signatures of biofilms (-33‰) and DIC (-9‰) in the anoxic water suggest in situ production by lithoautotrophs using RuBisCO. 16S rDNA libraries constructed from the biofilm are dominated by diverse sulfate reducing bacteria. The remaining bacterial and archaeal clones affiliate with more than 11 major uncultivated or novel prokaryotic lineages. Diverse dsrAB gene sequences are consistent with high sulfate concentrations and undetectable or extremely low oxygen, nitrate, and iron concentrations. However, the electron donor for sulfate reduction is unclear. Methane is detectable in the anoxic water although no 16S rDNA sequences associated with known methanogens or anaerobic methane oxidizers were retrieved. mcrA gene sequences retrieved from the biofilm by cloning are not related to cultivated methanogens or to known anaerobic methane oxidizers. Non-purgable organic carbon (NPOC) is below detection limits (i.e. <42 μM acetate) suggesting that alternative electron donors or novel metabolisms may be important. A sample collected by cave divers in October 2009 was pyrosequenced at the Pennsylvania State University Genomics Core Facility using Titanium chemistry (454 Life

  12. Anaerobic Sulfur Metabolism Coupled to Dissimilatory Iron Reduction in the Extremophile Acidithiobacillus ferrooxidans

    PubMed Central

    Osorio, Héctor; Mangold, Stefanie; Denis, Yann; Ñancucheo, Ivan; Esparza, Mario; Johnson, D. Barrie; Bonnefoy, Violaine; Dopson, Mark

    2013-01-01

    Gene transcription (microarrays) and protein levels (proteomics) were compared in cultures of the acidophilic chemolithotroph Acidithiobacillus ferrooxidans grown on elemental sulfur as the electron donor under aerobic and anaerobic conditions, using either molecular oxygen or ferric iron as the electron acceptor, respectively. No evidence supporting the role of either tetrathionate hydrolase or arsenic reductase in mediating the transfer of electrons to ferric iron (as suggested by previous studies) was obtained. In addition, no novel ferric iron reductase was identified. However, data suggested that sulfur was disproportionated under anaerobic conditions, forming hydrogen sulfide via sulfur reductase and sulfate via heterodisulfide reductase and ATP sulfurylase. Supporting physiological evidence for H2S production came from the observation that soluble Cu2+ included in anaerobically incubated cultures was precipitated (seemingly as CuS). Since H2S reduces ferric iron to ferrous in acidic medium, its production under anaerobic conditions indicates that anaerobic iron reduction is mediated, at least in part, by an indirect mechanism. Evidence was obtained for an alternative model implicating the transfer of electrons from S0 to Fe3+ via a respiratory chain that includes a bc1 complex and a cytochrome c. Central carbon pathways were upregulated under aerobic conditions, correlating with higher growth rates, while many Calvin-Benson-Bassham cycle components were upregulated during anaerobic growth, probably as a result of more limited access to carbon dioxide. These results are important for understanding the role of A. ferrooxidans in environmental biogeochemical metal cycling and in industrial bioleaching operations. PMID:23354702

  13. [Effect of dinitrosyl iron complexes on erythrocyte energy metabolism under thermal trauma conditions].

    PubMed

    Martusevich, A K; Solov'eva, A G; Peretiagin, S P; Vanin, A F

    2014-01-01

    The effect of dinitrosyl iron complexes (DNIC) on the energy metabolism of erythrocytes under combined thermal trauma conditions has been studied on a group of 30 Wistar rats, which was divided into 3 groups: intact (n = 10), control (n = 10), and main (n = 10). Combined thermal trauma (skin burn + thermoinhalation damage) was modeled in animals of the control and main groups. Rats of control group received infusions of sodium chloride solution (n = 10) every day. Rats of the main group obtained infusions of DNIC solution in sodium chloride. Rat blood samples were characterized by the activity of lactate dehydrogenase in direct and reverse reaction, lactate level, and coefficients of the substrate provision and energy reactions balance. It was stated, that DNIC clearly normalized the energy metabolism of erythrocytes beginning with the third day after thermal trauma onset. PMID:24791335

  14. The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism.

    PubMed

    Braithwaite, V S; Prentice, A; Darboe, M K; Prentice, A M; Moore, S E

    2016-02-01

    Fibroblast growth factor-23 (FGF23), a phosphate(Phos)-regulating hormone, is abnormally elevated in hypophosphataemic syndromes and an elevated FGF23 is a predictor of mortality in kidney disease. Recent findings suggest iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on offspring FGF23 and phosphate metabolism. Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first 2years of life. Infants born to mothers with normal (NIn=25,) and low (LIn=25) iron status during pregnancy, from a mother-infant trial (ISRCTN49285450) in rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104weeks (wk) of age. Circulating intact-FGF23 (I-FGF23), Phos, total alkaline phosphatase (TALP) and haemoglobin (Hb) decreased and estimated glomerular filtration rate increased over time [all P≤0.0001)]. C-terminal-FGF23 (C-FGF23) and TALP were significantly higher in LI compared with NI, from 52wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P=0.04] and from 24wk for TALP [44.7 (29.6) U/L, P=0.04]. Infant Hb was the strongest negative predictor of C-FGF23 concentration [-21% (4%) RU/mL, P≤0.0001], Phos was the strongest positive predictor of I-FGF23 [32.0(3.9) pg/mL, P≤0.0001] and I-FGF23 did not predict C-FGF23 over time [-0.5% (0.5%), P=0.3]. In conclusion, this study suggests that poor maternal iron status is associated with a higher infant C-FGF23 and TALP but similar I-FGF23 concentrations in infants and young children. These findings further highlight the likely public health importance of preventing iron deficiency during pregnancy. Whether or not children who are born to iron deficient mothers have persistently high concentrations of these metabolites and are more likely to be at risk of impaired bone development and pre-disposed to rickets requires further research. PMID:26453792

  15. Low iron availability and phenolic metabolism in a wild plant species (Parietaria judaica L.).

    PubMed

    Tato, Liliana; De Nisi, Patrizia; Donnini, Silvia; Zocchi, Graziano

    2013-11-01

    Plant phenolics encompass a wide range of aromatic compounds and functions mainly related to abiotic and biotic environmental responses. In calcareous soils, the presence of bicarbonate and a high pH cause a decrease in iron (Fe) bioavailability leading to crop yield losses both qualitatively and quantitatively. High increases in phenolics were reported in roots and root exudates as a consequence of decreased Fe bioavailability suggesting their role in chelation and reduction of inorganic Fe(III) contributing to the mobilization of Fe oxides in soil and plant apoplast. Shikimate pathway represents the main pathway to provide aromatic precursors for the synthesis of phenylpropanoids and constitutes a link between primary and secondary metabolism. Thus the increased level of phenolics suggests a metabolic shift of carbon skeletons from primary to secondary metabolism. Parietaria judaica, a spontaneous plant well adapted to calcareous environments, demonstrates a high metabolic flexibility in response to Fe starvation. Plants grown under low Fe availability conditions showed a strong accumulation of phenolics in roots as well as an improved secretion of root exudates. P. judaica exhibits enhanced enzymatic activities of the shikimate pathway. Furthermore, the non-oxidative pentose phosphate pathway, through the transketolase activity supplies erythrose-4-phosphate, is strongly activated. These data may indicate a metabolic rearrangement modifying the allocation of carbon skeletons between primary and secondary metabolism and the activation of a nonoxidative way to overcome a mitochondrial impairment. We suggest that high content of phenolics in P. judaica play a crucial role in its adaptive strategy to cope with low Fe availability. PMID:23769379

  16. Transcriptional and translational regulatory responses to iron limitation in the globally distributed marine bacterium Candidatus Pelagibacter ubique

    SciTech Connect

    Smith, Daniel P.; Kitner, J. B.; Norbeck, Angela D.; Clauss, Therese RW; Lipton, Mary S.; Schwalbach, M. S.; Steindler, L.; Nicora, Carrie D.; Smith, Richard D.; Giovannoni, Stephen J.

    2010-05-05

    Abstract Background: Iron is recognized as an important micronutrient that limits microbial plankton productivity over vast regions of the oceans. We investigated the gene expression responses of Candidatus Pelagibacter ubique cultures to iron limitation in natural seawater media supplemented with a siderophore to chelate iron. Methodology/Principal Findings: Microarray data indicated transcription of the periplasmic iron binding protein sfuC increased by 16-fold, and iron transporter subunits, iron-sulfur center assembly genes, and the putative ferroxidase rubrerythrin transcripts increased to a lesser extent. Quantitative peptide mass spectrometry revealed that sfuC protein abundance increased 27-fold, despite an average decrease of 59% across the global proteome. Two RNA-binding proteins, CspE and CspL, correlated well with iron availability, suggesting that they may contribute to the observed differences between the transcriptome and proteome. Conclusions/Significance: We propose sfuC as a marker gene for indicating iron limitation in marine metatranscriptomic and metaproteomic ecological surveys. The marked proteome reduction was not directly correlated to changes in the transcriptome, implicating post-transcriptional regulatory mechanisms as modulators of protein expression. We propose a model in which the RNA-binding activity of cspE and cspL selectively enables protein synthesis of the iron acquisition protein sfuC during transient growth-limiting episodes of iron scarcity.

  17. Disturbed iron metabolism among workers exposed to organic sulfides in a pulp plant.

    PubMed

    Klingberg, J; Beviz, A; Ohlson, C G; Tenhunen, R

    1988-02-01

    The aim of this study was to investigate a possible relationship between exposure to sulfides and disturbances of the synthesis of heme and the erythrocytes. Eighteen workers exposed to sulfides at a pulp and paper plant were examined and compared with individually matched referents from a thermomechanical pulp plant without such exposure. The exposure levels of methylmercaptan, dimethylsulfide, and dimethyldisulfide were low. However, five subjects were exposed to high levels of short duration, and their data were analyzed separately. The activity of the enzymes delta-aminolevulinic acid synthase and heme synthase in reticulocytes, characteristics of the erythrocytes, and the iron status were analyzed. A minor decrease, not statistically significant, was observed for the enzymes among the five highly exposed subjects. However, the concentrations of iron and transferrin were elevated and the concentration of ferritin was low in comparison to the corresponding levels of the referents. This combination will not occur spontaneously. A previous study indicated that sulfides may inhibit heme synthesis, and the present study suggests that they may also disturb iron metabolism. PMID:3353691

  18. Viability of pyrite pulled metabolism in the ‘iron-sulfur world’ theory: Quantum chemical assessment

    NASA Astrophysics Data System (ADS)

    Michalkova, Andrea; Kholod, Yana; Kosenkov, Dmytro; Gorb, Leonid; Leszczynski, Jerzy

    2011-04-01

    The viability of pyrite-pulled metabolism in the 'iron-sulfur world' theory was assessed using a simple model of iron-nickel sulfide (Fe-Ni-S) surface and data obtained from quantum chemical calculations. We have investigated how the individual reactions in the carbon fixation cycle (carboxylic acids formation) on an Fe-Ni-S surface could have operated to produce carboxylic acids from carbon oxide and water. The proposed model cycle reveals how the individual reactions might have functioned and provides the thermodynamics of each step of the proposed pathway. The feasibility of individual reactions, as well the whole cycle was considered. The reaction of acetic acid production from CH 3SH and CO on an Fe-Ni sulfide surface was revealed to be endergonic with a few partial steps having positive Gibbs free energy. On the other hand, the pyrite formation was found to be slightly exergonic. The significance of the catalytic activity of transition metal sulfides in generation of acetic acid was shown. The Gibbs free energy values indicate that the acetic acid synthesis is unfavorable to proceed on the studied Fe-Ni-S model under simulated conditions. The importance of these results in terms of a primordial chemistry on iron-nickel sulfide surfaces is discussed.

  19. Iron pentacarbonyl detection limits in the cigarette smoke matrix using FT-IR spectroscopy

    NASA Astrophysics Data System (ADS)

    Parrish, Milton E.; Plunkett, Susan E.; Harward, Charles N.

    2005-11-01

    Endogenous metals present in tobacco from agricultural practices have been purported to generate metal carbonyls in cigarette smoke. Transition metal catalysts, such as iron oxide, have been investigated for the reduction of carbon monoxide (CO) in cigarette smoke. These studies motivated the development of an analytical method to determine if iron pentacarbonyl [Fe(CO) 5] is present in mainstream smoke from cigarette models having cigarette paper made with iron oxide. An FT-IR puff-by-puff method was developed and the detection limit was determined using two primary reference spectra from different sources to estimate the amount of Fe(CO) 5 present in a high-pressure steel cylinder of CO. We do not detect Fe(CO) 5 in a single 35 mL puff from reference cigarettes or from those cigarette models having cigarette paper made with iron oxide, with a 30-ppbV limit of detection (LOD). Also, it was shown that a filter containing activated carbon would remove Fe(CO) 5.

  20. Iron Status and Metabolic Syndrome in Patients with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Ghamarchehreh, Mohammad Ebrahim; Jonaidi-Jafari, Nematollah; Bigdeli, Mohammad; Khedmat, Hossein; Saburi, Amin

    2016-01-01

    BACKGROUND A hypothesis has been presented about the role of serum iron, ferritin and transferrin saturation among patients with non-alcoholic fatty liver disease (NAFLD) and resistance to insulin (metabolic syndrome [MetS]), but there is much controversy. This study aimed at investigating the level of serum iron and demographic characteristics in patients with NAFLD with or without MetS. METHODS A case-control study was conducted on patients with elevated liver enzymes referring to Baqiyatallah clinic, Tehran, Iran during 2010-2011. After ruling out other causes of increased aminotransferases and approving the diagnosis of NAFLD, the patients were divided into two groups of with or without MetS. Then, the individuals’ demographic, sonographic, and laboratory characteristics were recorded. RESULTS This research included 299 patients suffering from NAFLD who were divided into MetS (n=143; 47.8%) and non-MetS (n=156; 52.2%) groups. The age, systolic and diastolic blood pressure, body mass index, waist/hip ratio, glucose tolerance test, serum insulin, C. peptide, triglyceride, and HB A1c were different between MetS and non-MetS groups (p<0.05). There was no significant difference in serum iron and ferritin levels between the two groups, however, a significant correlation was found between serum ferritin and alanine transaminase (p=0.005) and also aspartate aminotransferase (p=0.032). CONCLUSION Our findings did not show a significant relationship between iron, in free or storage form, and the presence of MetS among patients with NAFLD, but serum ferritin can correlate with hepatocytes injuries indicated by raised aminotransferases. Nevertheless, to clarify this relationship further molecular, genomic, and histopathological studies are required. PMID:26933479

  1. IRON

    EPA Science Inventory

    The document surveys the effects of organic and inorganic iron that are relevant to humans and their environment. The biology and chemistry of iron are complex and only partially understood. Iron participates in oxidation reduction processes that not only affect its geochemical m...

  2. The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

    PubMed Central

    Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

    2014-01-01

    Background Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. Objectives To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Methods Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Results Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. Conclusions No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally. PMID:24988074

  3. Reserve carbohydrate metabolism in Saccharomyces cerevisiae: responses to nutrient limitation.

    PubMed Central

    Lillie, S H; Pringle, J R

    1980-01-01

    The amounts of glycogen and trehalose have been measured in cells of a prototrophic diploid yeast strain subjected to a variety of nutrient limitations. Both glycogen and trehalose were accumulated in cells deprived specifically of nirogen, sulfur, or phosphorus, suggesting that reserve carbohydrate accumulation is a general response to nutrient limitation. The patterns of accumulation and utilization of glycogen and trehalose were not identical under these conditions, suggesting that the two carbohydrates may play distinct physiological roles. Glycogen and trehalose were also accumulated by cells undergoing carbon and energy limitation, both during diauxic growth in a relatively poor medium and during the approach to stationary phase in a rich medium. Growth in the rich medium was shown to be carbon or energy limited or both, although the interaction between carbon source limitation and oxygen limitation was complex. In both media, the pattern of glycogen accumulation and utilization was compatible with its serving as a source of energy both during respiratory adaptation and during a subsequent starvation. In contrast, the pattern of trehalose accumulation and utilization seemed compatible only with the latter role. In cultures that were depleting their supplies of exogenous glucose, the accumulation of glycogen began at glucose concentrations well above those sufficient to suppress glycogen accumulation in cultures growing with a constant concentration of exogenous glucose. The mechanism of this effect is not clear, but may involve a response to the rapid rate of change in the glucose concentration. PMID:6997270

  4. An energetic model for oxygen-limited metabolism

    SciTech Connect

    Beronio, P.B. Jr. . Amoco Research Center); Tsao, G.T. . Lab. of Renewable Resources Engineering)

    1993-12-01

    Microbial production of 2,3-butanediol by Klebsiella oxytoca occurs under conditions of an oxygen limitation. The extent to which substrate is oxidized to 2,3-butanediol and its coproducts, (acetic acid, acetoin, and ethanol) and the relative flow rates of substrate to energetic and biosynthetic pathways are controlled by the degree of oxygen limitation. Two energetic relationships which describe the response to an oxygen limitation have been derived. The first relationship describes the coupling between growth and energy production observed under oxygen-limited conditions. This allows calculation of energetic parameters and modeling of the cell mass and substrate profiles in terms of the degree of oxygen limitation only. The second relationship describes the average degree of oxidation and the rate of the end-product flow. The model has been tested with both batch and continuous culture. During these kinetic studies, two phases of growth have been observed: energy-coupled growth, which was described above; and, energy-uncoupled growth, which arises when the degree of oxygen limitation reaches a critical value. Optimal culture performance with respect to 2,3-butanediol productivity occurs during energy-coupled growth.

  5. Ferric reduction by iron-limited Chlamydomonas cells interacts with both photosynthesis and respiration.

    PubMed

    Weger, H G; Espie, G S

    2000-04-01

    Iron limitation led to a large increase in extracellular ferricyanide (Fe[III]) reductase activity in cells of the green alga Chlamydomonas reinhardtii Dangeard. Mass-spectrometric measurement of gas exchange indicated that ferricyanide reduction in the dark resulted in a stimulation of respiratory CO2 production without affecting the rate of respiratory O2 consumption, consistent with the previously postulated activation of the oxidative pentose phosphate pathway in support of Fe(III) reduction by iron-limited Chlamydomonas cells (X. Xue et al., 1998, J. Phycol. 34: 939-944). At saturating irradiance, the rate of ferricyanide reduction was stimulated almost 3-fold, and this stimulation was inhibited by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea. Ferricyanide reduction during photosynthesis resulted in approximately a 50% inhibition of photosynthetic CO2 fixation at saturating irradiance, and almost 100% inhibition of CO2 fixation at sub-saturating irradiance. Photosynthesis by iron-sufficient cells was not affected by ferricyanide addition. Addition of 250 microM ferricyanide to iron-limited cells in which photosynthesis was inhibited (either by the presence of glycolaldehyde, or by maintaining the cells at the CO2 compensation point) resulted in a stimulation in the rate of gross photosynthetic O2 evolution. Chlorophyll a fluorescence measurements indicated a large increase in non-photochemical quenching during ferricyanide reduction in the light; the increase in nonphotochemical quenching was abolished by the addition of nigericin. These results suggest that reduction of extracellular ferricyanide (mediated at the plasma membrane) interacts with both photosynthesis and respiration, and that both of these processes contribute NADPH in the light. PMID:10805449

  6. Mouse handling limits the impact of stress on metabolic endpoints.

    PubMed

    Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G; Smith, Eric P; Tong, Jenny; D'Alessio, David A; Herman, James P

    2015-10-15

    Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). PMID:26079207

  7. Knocking down mitochondrial iron transporter (MIT) reprograms primary and secondary metabolism in rice plants.

    PubMed

    Vigani, Gianpiero; Bashir, Khurram; Ishimaru, Yasuhiro; Lehmann, Martin; Casiraghi, Fabio Marco; Nakanishi, Hiromi; Seki, Motoaki; Geigenberger, Peter; Zocchi, Graziano; Nishizawa, Naoko K

    2016-03-01

    Iron (Fe) is an essential micronutrient for plant growth and development, and its reduced bioavailability strongly impairs mitochondrial functionality. In this work, the metabolic adjustment in the rice (Oryza sativa) mitochondrial Fe transporter knockdown mutant (mit-2) was analysed. Biochemical characterization of purified mitochondria from rice roots showed alteration in the respiratory chain of mit-2 compared with wild-type (WT) plants. In particular, proteins belonging to the type II alternative NAD(P)H dehydrogenases accumulated strongly in mit-2 plants, indicating that alternative pathways were activated to keep the respiratory chain working. Additionally, large-scale changes in the transcriptome and metabolome were observed in mit-2 rice plants. In particular, a strong alteration (up-/down-regulation) in the expression of genes encoding enzymes of both primary and secondary metabolism was found in mutant plants. This was reflected by changes in the metabolic profiles in both roots and shoots of mit-2 plants. Significant alterations in the levels of amino acids belonging to the aspartic acid-related pathways (aspartic acid, lysine, and threonine in roots, and aspartic acid and ornithine in shoots) were found that are strictly connected to the Krebs cycle. Furthermore, some metabolites (e.g. pyruvic acid, fumaric acid, ornithine, and oligosaccharides of the raffinose family) accumulated only in the shoot of mit-2 plants, indicating possible hypoxic responses. These findings suggest that the induction of local Fe deficiency in the mitochondrial compartment of mit-2 plants differentially affects the transcript as well as the metabolic profiles in root and shoot tissues. PMID:26685186

  8. Knocking down mitochondrial iron transporter (MIT) reprograms primary and secondary metabolism in rice plants

    PubMed Central

    Vigani, Gianpiero; Bashir, Khurram; Ishimaru, Yasuhiro; Lehmann, Martin; Casiraghi, Fabio Marco; Nakanishi, Hiromi; Seki, Motoaki; Geigenberger, Peter; Zocchi, Graziano; Nishizawa, Naoko K.

    2016-01-01

    Iron (Fe) is an essential micronutrient for plant growth and development, and its reduced bioavailability strongly impairs mitochondrial functionality. In this work, the metabolic adjustment in the rice (Oryza sativa) mitochondrial Fe transporter knockdown mutant (mit-2) was analysed. Biochemical characterization of purified mitochondria from rice roots showed alteration in the respiratory chain of mit-2 compared with wild-type (WT) plants. In particular, proteins belonging to the type II alternative NAD(P)H dehydrogenases accumulated strongly in mit-2 plants, indicating that alternative pathways were activated to keep the respiratory chain working. Additionally, large-scale changes in the transcriptome and metabolome were observed in mit-2 rice plants. In particular, a strong alteration (up-/down-regulation) in the expression of genes encoding enzymes of both primary and secondary metabolism was found in mutant plants. This was reflected by changes in the metabolic profiles in both roots and shoots of mit-2 plants. Significant alterations in the levels of amino acids belonging to the aspartic acid-related pathways (aspartic acid, lysine, and threonine in roots, and aspartic acid and ornithine in shoots) were found that are strictly connected to the Krebs cycle. Furthermore, some metabolites (e.g. pyruvic acid, fumaric acid, ornithine, and oligosaccharides of the raffinose family) accumulated only in the shoot of mit-2 plants, indicating possible hypoxic responses. These findings suggest that the induction of local Fe deficiency in the mitochondrial compartment of mit-2 plants differentially affects the transcript as well as the metabolic profiles in root and shoot tissues. PMID:26685186

  9. Initial Characterization of Carbon Metabolism in Iron Oxidizing Microbial Communities of Acidic Hot Springs in Norris Geyser Basin, Yellowstone National Park

    NASA Astrophysics Data System (ADS)

    Kreuzer, H. W.; Jennings, R. D.; Whitmore, L.; Inskeep, W. P.; Moran, J.

    2012-12-01

    Norris Geyser Basin in Yellowstone National Park is home to several acidic, sulfidic hot springs. Visual inspection of the springs reveals distinct geochemical regions starting with a sulfur deposition zone followed by a transition to iron oxide deposition downstream. The microbial communities in the iron oxidation zones are dominated by Archaea, including several members that appear to define previously unrecognized taxa. Abiotic iron oxidation rates are very slow at these temperatures (typically ~ 65-70 oC) and pH's (typically ~3). Therefore, the relatively rapid iron oxide deposition rate strongly suggests the process is microbially mediated, and an organism previously isolated from these springs, Metallosphaera yellowstonensis, has been shown to oxide iron in culture. M. yellowstonensis has been observed in the all microbial communities analyzed in the iron oxidizing zones of these springs, though metagenomic profiling suggests it constitutes only ~20% of the community membership. When we began our studies of C flow in the iron-oxidizing community, no C source had been demonstrated. Observed potential carbon sources in the springs include dissolved inorganic carbon, dissolved organic carbon, and methane, as well as random inputs of heterotrophic carbon in the forms of insect carcasses, pine needles, and animal scat. The temperatures in the iron oxidation zones are above the photosynthetic upper temperature limit, thus precluding photosynthetic-based autotrophy within the community itself. We are employing geochemical and stable isotope techniques to assess carbon inventories in the system. We have demonstrated that M. yellowstonensis as well as excised samples of iron oxide mat communities can fix CO2, and our estimated isotopic fractionation factor is consistent with the 3-hydroxypropionate 4-hydroxybutyrate pathway. Genes of this pathway have been identified in the M. yellowstonensis genome. We have tentatively identified small amounts of organic compounds

  10. Iron metabolism in African American women during the 2nd and 3rd trimester of a high-risk pregnancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To examine iron metabolism during the 2nd and 3rd trimester in African American women classified as a high-risk pregnancy. Design: Longitudinal. Setting: Large, university-based, urban Midwestern medical center. Participants: Convenience sample of 47 African American women classified a...

  11. Purification and structural characterization of a flavoprotein induced by iron limitation in Methanobacterium thermoautotrophicum Marburg.

    PubMed Central

    Wasserfallen, A; Huber, K; Leisinger, T

    1995-01-01

    Cells of Methanobacterium thermoautotrophicum (strain Marburg) grown under iron-limiting conditions were found to synthesize a soluble polypeptide as one of the major cell proteins. This polypeptide purified as a homotetramer (170 kDa [subunit molecular mass, 43 kDa]) had a UV-visible spectrum typical of flavoproteins and contained 0.7 mol of flavin mononucleotide per mol of monomer. Quantitative analysis by immunoblotting with polyclonal antibodies indicated that the flavoprotein, which amounts to about 0.6% of soluble cell protein under iron-sufficient conditions (> or = 50 microM Fe2+), was induced fivefold by iron limitation (< 12 microM Fe2+). The flavoprotein-encoding gene, fprA, was cloned and sequenced. Sequence analysis revealed a well-conserved archaebacterial consensus promoter upstream of fprA, a flavodoxin signature within fprA, and 28% amino acid identity with a putative flavin mononucleotide-containing protein of Rhodobacter capsulatus which is found within an operon involved in nitrogen fixation. A possible physiological function for the flavoprotein is discussed. PMID:7730275

  12. Mitochondrial ferritin suppresses MPTP-induced cell damage by regulating iron metabolism and attenuating oxidative stress.

    PubMed

    You, Lin-Hao; Li, Zhen; Duan, Xiang-Lin; Zhao, Bao-Lu; Chang, Yan-Zhong; Shi, Zhen-Hua

    2016-07-01

    Our previous work showed that mitochondrial ferritin (MtFt) played an important role in preventing neuronal damage in 6-OHDA-induced Parkinson's disease (PD). However, the role of MtFt in a PD model induced by MPTP is not clear. Here, we found that methyl-4-phenyl-1, 2, 3, 6-tetra-pyridine (MPTP) significantly upregulated MtFt in the mouse hippocampus, substantia nigra (SN) and striatum. To explore the effect of MtFt upregulation on the MPTP-mediated injury to neural cells, MtFt-/- mice and MtFt-overexpressing cells were used to construct models of PD induced by MPTP. Our results showed that MPTP dramatically downregulated expression of transferrin receptor 1 (TfR1) and tyrosine hydroxylase and upregulated L-ferritin expression in the mouse striatum and SN. Interestingly, MPTP induced high levels of MtFt in these tissues, indicating that MtFt was involved in iron metabolism and influenced dopamine synthesis induced by MPTP. Meanwhile, the Bcl2/Bax ratio was decreased significantly by MPTP in the striatum and SN of MtFt knockout (MtFt-/-) mice compared with controls. Overexpression of MtFt increased TfR1 and decreased ferroportin 1 induced by 1-methyl-4-phenylpyridinium ions (MPP+). MtFt strongly inhibited mitochondrial damage through maintaining the mitochondrial membrane potential and protecting the integrity of the mitochondrial membrane. It also suppressed the increase of the labile iron pool, decreased production of reactive oxygen species and dramatically rescued the apoptosis induced by MPP+. In conclusion, this study demonstrates that MtFt plays an important role in preventing neuronal damage in the MPTP-induced parkinsonian phenotype by inhibiting cellular iron accumulation and subsequent oxidative stress. PMID:27017962

  13. Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood.

    PubMed

    Peslova, Gabriela; Petrak, Jiri; Kuzelova, Katerina; Hrdy, Ivan; Halada, Petr; Kuchel, Philip W; Soe-Lin, Shan; Ponka, Prem; Sutak, Robert; Becker, Erika; Huang, Michael Li-Hsuan; Suryo Rahmanto, Yohan; Richardson, Des R; Vyoral, Daniel

    2009-06-11

    Hepcidin is a major regulator of iron metabolism. Hepcidin-based therapeutics/diagnostics could play roles in hematology in the future, and thus, hepcidin transport is crucial to understand. In this study, we identify alpha2-macroglobulin (alpha2-M) as the specific hepcidin-binding molecule in blood. Interaction of 125I-hepcidin with alpha2-M was identified using fractionation of plasma proteins followed by native gradient polyacrylamide gel electrophoresis and mass spectrometry. Hepcidin binding to nonactivated alpha2-M displays high affinity (Kd 177 +/- 27 nM), whereas hepcidin binding to albumin was nonspecific and displayed nonsaturable kinetics. Surprisingly, the interaction of hepcidin with activated alpha2-M exhibited a classical sigmoidal binding curve demonstrating cooperative binding of 4 high-affinity (Kd 0.3 microM) hepcidin-binding sites. This property probably enables efficient sequestration of hepcidin and its subsequent release or inactivation that may be important for its effector functions. Because alpha2-M rapidly targets ligands to cells via receptor-mediated endocytosis, the binding of hepcidin to alpha2-M may influence its functions. In fact, the alpha2-M-hepcidin complex decreased ferroportin expression in J774 cells more effectively than hepcidin alone. The demonstration that alpha2-M is the hepcidin transporter could lead to better understanding of hepcidin physiology, methods for its sensitive measurement and the development of novel drugs for the treatment of iron-related diseases. PMID:19380872

  14. Effects of Radiation and Dietary Iron on Expression of Genes and Proteins Involved in Drug Metabolism

    NASA Technical Reports Server (NTRS)

    Faust, K. M.; Wotring, V. E.

    2014-01-01

    Liver function, especially the rate of metabolic enzyme activities, determines the concentration of circulating drugs and the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Dietary factors and exposure to radiation are aspects of spaceflight that are potential oxidative stressors and both can be modeled in ground experiments. In this experiment, we examined the effects of high dietary iron and low dose gamma radiation (individually and combined) on the gene expression of enzymes involved in drug metabolism, redox homeostasis, and DNA repair. METHODS All procedures were approved by the JSC Animal Care and Use Committee. Male Sprague-Dawley rats were divided into 4 groups (n=8); control, high Fe diet (650 mg iron/kg), radiation (fractionated 3 Gy exposure from a Cs- 137 source) and combined high Fe diet + radiation exposure. Animals were euthanized 24h after the last treatment of radiation; livers were removed immediately and flash -frozen in liquid nitrogen. Expression of genes thought to be involved in redox homeostasis, drug metabolism and DNA damage repair was measured by RT-qPCR. Where possible, protein expression of the same genes was measured by western blotting. All data are expressed as % change in expression normalized to reference gene expression; comparisons were then made of each treatment group to the sham exposed/ normal diet control group. Data was considered significant at p< 0

  15. Evidence for a metabolic limitation of survival in hypothermic hamsters.

    NASA Technical Reports Server (NTRS)

    Prewitt, R. L.; Anderson, G. L.; Musacchia, X. J.

    1972-01-01

    The underlying factors limiting survival in the hypothermic state are studied. Hamsters of both sexes, clipped and unclipped, were inducted into profound hypothermia by the helium cold method until they reached a temperature between 7 and 10 C. It appears that the primary cause of death is failure of respiration due to the depletion of carbohydrate energy supplies and may explain why survival time in hypothermia is shorter than the normal hibernation time of the hamster.

  16. Iron Limitation of a Springtime Bacterial and Phytoplankton Community in the Ross Sea: Implications for Vitamin B12 Nutrition

    PubMed Central

    Bertrand, Erin M.; Saito, Mak A.; Lee, Peter A.; Dunbar, Robert B.; Sedwick, Peter N.; DiTullio, Giacomo R.

    2011-01-01

    The Ross Sea is home to some of the largest phytoplankton blooms in the Southern Ocean. Primary production in this system has previously been shown to be iron limited in the summer and periodically iron and vitamin B12 colimited. In this study, we examined trace metal limitation of biological activity in the Ross Sea in the austral spring and considered possible implications for vitamin B12 nutrition. Bottle incubation experiments demonstrated that iron limited phytoplankton growth in the austral spring while B12, cobalt, and zinc did not. This is the first demonstration of iron limitation in a Phaeocystis antarctica-dominated, early season Ross Sea phytoplankton community. The lack of B12 limitation in this location is consistent with previous Ross Sea studies in the austral summer, wherein vitamin additions did not stimulate P. antarctica growth and B12 was limiting only when bacterial abundance was low. Bottle incubation experiments and a bacterial regrowth experiment also revealed that iron addition directly enhanced bacterial growth. B12 uptake measurements in natural water samples and in an iron fertilized bottle incubation demonstrated that bacteria serve not only as a source for vitamin B12, but also as a significant sink, and that iron additions enhanced B12 uptake rates in phytoplankton but not bacteria. Additionally, vitamin uptake rates did not become saturated upon the addition of up to 95 pM B12. A rapid B12 uptake rate was observed after 13 min, which then decreased to a slower constant uptake rate over the next 52 h. Results from this study highlight the importance of iron availability in limiting early season Ross Sea phytoplankton growth and suggest that rates of vitamin B12 production and consumption may be impacted by iron availability. PMID:21886638

  17. Iron limitation of a springtime bacterial and phytoplankton community in the ross sea: implications for vitamin b(12) nutrition.

    PubMed

    Bertrand, Erin M; Saito, Mak A; Lee, Peter A; Dunbar, Robert B; Sedwick, Peter N; Ditullio, Giacomo R

    2011-01-01

    The Ross Sea is home to some of the largest phytoplankton blooms in the Southern Ocean. Primary production in this system has previously been shown to be iron limited in the summer and periodically iron and vitamin B(12) colimited. In this study, we examined trace metal limitation of biological activity in the Ross Sea in the austral spring and considered possible implications for vitamin B(12) nutrition. Bottle incubation experiments demonstrated that iron limited phytoplankton growth in the austral spring while B(12), cobalt, and zinc did not. This is the first demonstration of iron limitation in a Phaeocystis antarctica-dominated, early season Ross Sea phytoplankton community. The lack of B(12) limitation in this location is consistent with previous Ross Sea studies in the austral summer, wherein vitamin additions did not stimulate P. antarctica growth and B(12) was limiting only when bacterial abundance was low. Bottle incubation experiments and a bacterial regrowth experiment also revealed that iron addition directly enhanced bacterial growth. B(12) uptake measurements in natural water samples and in an iron fertilized bottle incubation demonstrated that bacteria serve not only as a source for vitamin B(12), but also as a significant sink, and that iron additions enhanced B(12) uptake rates in phytoplankton but not bacteria. Additionally, vitamin uptake rates did not become saturated upon the addition of up to 95 pM B(12). A rapid B(12) uptake rate was observed after 13 min, which then decreased to a slower constant uptake rate over the next 52 h. Results from this study highlight the importance of iron availability in limiting early season Ross Sea phytoplankton growth and suggest that rates of vitamin B(12) production and consumption may be impacted by iron availability. PMID:21886638

  18. ideR, an Essential Gene in Mycobacterium tuberculosis: Role of IdeR in Iron-Dependent Gene Expression, Iron Metabolism, and Oxidative Stress Response†

    PubMed Central

    Rodriguez, G. Marcela; Voskuil, Martin I.; Gold, Benjamin; Schoolnik, Gary K.; Smith, Issar

    2002-01-01

    The mycobacterial IdeR protein is a metal-dependent regulator of the DtxR (diphtheria toxin repressor) family. In the presence of iron, it binds to a specific DNA sequence in the promoter regions of the genes that it regulates, thus controlling their transcription. In this study, we provide evidence that ideR is an essential gene in Mycobacterium tuberculosis. ideR cannot normally be disrupted in this mycobacterium in the absence of a second functional copy of the gene. However, a rare ideR mutant was obtained in which the lethal effects of ideR inactivation were alleviated by a second-site suppressor mutation and which exhibited restricted iron assimilation capacity. Studies of this strain and a derivative in which IdeR expression was restored allowed us to identify phenotypic effects resulting from ideR inactivation. Using DNA microarrays, the iron-dependent transcriptional profiles of the wild-type, ideR mutant, and ideR-complemented mutant strains were analyzed, and the genes regulated by iron and IdeR were identified. These genes encode a variety of proteins, including putative transporters, proteins involved in siderophore synthesis and iron storage, members of the PE/PPE family, a membrane protein involved in virulence, transcriptional regulators, and enzymes involved in lipid metabolism. PMID:12065475

  19. Drosophila mitoferrin is essential for male fertility: evidence for a role of mitochondrial iron metabolism during spermatogenesis

    PubMed Central

    2010-01-01

    Background Mammals and Drosophila melanogaster share some striking similarities in spermatogenesis. Mitochondria in spermatids undergo dramatic morphological changes and syncytial spermatids are stripped from their cytoplasm and then individually wrapped by single membranes in an individualization process. In mammalian and fruit fly testis, components of the mitochondrial iron metabolism are expressed, but so far their function during spermatogenesis is unknown. Here we investigate the role of Drosophila mitoferrin (dmfrn), which is a mitochondrial carrier protein with an established role in the mitochondrial iron metabolism, during spermatogenesis. Results We found that P-element insertions into the 5'-untranslated region of the dmfrn gene cause recessive male sterility, which was rescued by a fluorescently tagged transgenic dmfrn genomic construct (dmfrnvenus). Testes of mutant homozygous dmfrnSH115 flies were either small with unorganized content or contained some partially elongated spermatids, or testes were of normal size but lacked mature sperm. Testis squashes indicated that spermatid elongation was defective and electron micrographs showed mitochondrial defects in elongated spermatids and indicated failed individualization. Using a LacZ reporter and the dmfrnvenus transgene, we found that dmfrn expression in testes was highest in spermatids, coinciding with the stages that showed defects in the mutants. Dmfrn-venus protein accumulated in mitochondrial derivatives of spermatids, where it remained until most of it was stripped off during individualization and disposed of in waste bags. Male sterility in flies with the hypomorph alleles dmfrnBG00456 and dmfrnEY01302 over the deletion Df(3R)ED6277 was increased by dietary iron chelation and suppressed by iron supplementation of the food, while male sterility of dmfrnSH115/Df(3R)ED6277 flies was not affected by food iron levels. Conclusions In this work, we show that mutations in the Drosophila mitoferrin gene

  20. Iron and aluminium oxides containing industrial wastes as adsorbents of heavy metals: Application possibilities and limitations.

    PubMed

    Jacukowicz-Sobala, Irena; Ociński, Daniel; Kociołek-Balawejder, Elżbieta

    2015-07-01

    Industrial wastes with a high iron or aluminium oxide content are produced in huge quantities as by-products of water treatment (water treatment residuals), bauxite processing (red mud) and hard and brown coal burning in power plants (fly ash). Although they vary in their composition, the wastes have one thing in common--a high content of amorphous iron and/or aluminium oxides with a large specific surface area, whereby this group of wastes shows very good adsorbability towards heavy metals, arsenates, selenates, etc. But their physical form makes their utilisation quite difficult, since it is not easy to separate the spent sorbent from the solution and high bed hydraulic resistances occur in dynamic regime processes. Nevertheless, because of the potential benefits of utilising the wastes in industrial effluent treatment, this issue attracts much attention today. This study describes in detail the waste generation processes, the chemical structure of the wastes, their physicochemical properties, and the mechanisms of fixing heavy metals and semimetals on the surface of iron and aluminium oxides. Typical compositions of wastes generated in selected industrial plants are given. A detailed survey of the literature on the adsorption applications of the wastes, including methods of their thermal and chemical activation, as well as regeneration of the spent sorbents, is presented. The existing and potential ways of modifying the physical form of the discussed group of wastes, making it possible to overcome the basic limitation on their practical use, are discussed. PMID:26060197

  1. Iron acquisition in Leishmania and its crucial role in infection.

    PubMed

    Niu, Qinwang; Li, Shihong; Chen, Dali; Chen, Qiwei; Chen, Jianping

    2016-09-01

    Iron is an essential cofactor for many basic metabolic pathways in pathogenic microbes and their hosts. It is also dangerous as it can catalyse the production of reactive free radicals. This dual character makes the host can either limit iron availability to invading microbes or exploit iron to induce toxicity to pathogens. Successful pathogens, including Leishmania species, must possess mechanisms to circumvent host's iron limitation and iron-induced toxicity in order to survive. In this review, we discuss the regulation of iron metabolism in the setting of infection and delineate the iron acquisition strategies used by Leishmania parasites and their subversions to host iron metabolism to overcome host's iron-related defences. PMID:27221985

  2. Statistical analysis of iron geochemical data suggests limited late Proterozoic oxygenation

    NASA Astrophysics Data System (ADS)

    Sperling, Erik A.; Wolock, Charles J.; Morgan, Alex S.; Gill, Benjamin C.; Kunzmann, Marcus; Halverson, Galen P.; MacDonald, Francis A.; Knoll, Andrew H.; Johnston, David T.

    2015-07-01

    Sedimentary rocks deposited across the Proterozoic-Phanerozoic transition record extreme climate fluctuations, a potential rise in atmospheric oxygen or re-organization of the seafloor redox landscape, and the initial diversification of animals. It is widely assumed that the inferred redox change facilitated the observed trends in biodiversity. Establishing this palaeoenvironmental context, however, requires that changes in marine redox structure be tracked by means of geochemical proxies and translated into estimates of atmospheric oxygen. Iron-based proxies are among the most effective tools for tracking the redox chemistry of ancient oceans. These proxies are inherently local, but have global implications when analysed collectively and statistically. Here we analyse about 4,700 iron-speciation measurements from shales 2,300 to 360 million years old. Our statistical analyses suggest that subsurface water masses in mid-Proterozoic oceans were predominantly anoxic and ferruginous (depleted in dissolved oxygen and iron-bearing), but with a tendency towards euxinia (sulfide-bearing) that is not observed in the Neoproterozoic era. Analyses further indicate that early animals did not experience appreciable benthic sulfide stress. Finally, unlike proxies based on redox-sensitive trace-metal abundances, iron geochemical data do not show a statistically significant change in oxygen content through the Ediacaran and Cambrian periods, sharply constraining the magnitude of the end-Proterozoic oxygen increase. Indeed, this re-analysis of trace-metal data is consistent with oxygenation continuing well into the Palaeozoic era. Therefore, if changing redox conditions facilitated animal diversification, it did so through a limited rise in oxygen past critical functional and ecological thresholds, as is seen in modern oxygen minimum zone benthic animal communities.

  3. Statistical analysis of iron geochemical data suggests limited late Proterozoic oxygenation.

    PubMed

    Sperling, Erik A; Wolock, Charles J; Morgan, Alex S; Gill, Benjamin C; Kunzmann, Marcus; Halverson, Galen P; Macdonald, Francis A; Knoll, Andrew H; Johnston, David T

    2015-07-23

    Sedimentary rocks deposited across the Proterozoic-Phanerozoic transition record extreme climate fluctuations, a potential rise in atmospheric oxygen or re-organization of the seafloor redox landscape, and the initial diversification of animals. It is widely assumed that the inferred redox change facilitated the observed trends in biodiversity. Establishing this palaeoenvironmental context, however, requires that changes in marine redox structure be tracked by means of geochemical proxies and translated into estimates of atmospheric oxygen. Iron-based proxies are among the most effective tools for tracking the redox chemistry of ancient oceans. These proxies are inherently local, but have global implications when analysed collectively and statistically. Here we analyse about 4,700 iron-speciation measurements from shales 2,300 to 360 million years old. Our statistical analyses suggest that subsurface water masses in mid-Proterozoic oceans were predominantly anoxic and ferruginous (depleted in dissolved oxygen and iron-bearing), but with a tendency towards euxinia (sulfide-bearing) that is not observed in the Neoproterozoic era. Analyses further indicate that early animals did not experience appreciable benthic sulfide stress. Finally, unlike proxies based on redox-sensitive trace-metal abundances, iron geochemical data do not show a statistically significant change in oxygen content through the Ediacaran and Cambrian periods, sharply constraining the magnitude of the end-Proterozoic oxygen increase. Indeed, this re-analysis of trace-metal data is consistent with oxygenation continuing well into the Palaeozoic era. Therefore, if changing redox conditions facilitated animal diversification, it did so through a limited rise in oxygen past critical functional and ecological thresholds, as is seen in modern oxygen minimum zone benthic animal communities. PMID:26201598

  4. Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus.

    PubMed

    Carlson, Erik S; Stead, John D H; Neal, Charles R; Petryk, Anna; Georgieff, Michael K

    2007-01-01

    The human and rat hippocampus is highly susceptible to iron deficiency (ID) during the late fetal, early neonatal time period which is a peak time of regulated brain iron uptake and utilization. ID during this period alters cognitive development and is characterized by distinctive, long-term changes in hippocampal cellular growth and function. The fundamental processes underlying these changes are not entirely understood. In this study, ID-induced changes in expression of 25 genes implicated in iron metabolism, including cell growth and energy metabolism, dendrite morphogenesis, and synaptic connectivity were assessed from postnatal day (P) 7 to P65 in hippocampus. All 25 genes showed altered expression during the period of ID (P7, 15, and 30); 10 had changes on P65 after iron repletion. ID caused long-term diminished protein levels of four factors critical for hippocampal neuron differentiation and plasticity, including CamKII alpha, Fkbp1a (Fkbp12), Dlgh4 (PSD-95), and Vamp1 (Synaptobrevin-1). ID altered gene expression in the mammalian target of rapamycin (mTOR) pathway and in a gene network implicated in Alzheimer disease etiology. ID during late fetal and early postnatal life alters the levels and timing of expression of critical genes involved in hippocampal development and function. The study provides targets for future studies in elucidating molecular mechanisms underpinning iron's role in cognitive development and function. PMID:17546681

  5. Application of circuit simulation method for differential modeling of TIM-2 iron uptake and metabolism in mouse kidney cells.

    PubMed

    Xie, Zhijian; Harrison, Scott H; Torti, Suzy V; Torti, Frank M; Han, Jian

    2013-01-01

    Circuit simulation is a powerful methodology to generate differential mathematical models. Due to its highly accurate modeling capability, circuit simulation can be used to investigate interactions between the parts and processes of a cellular system. Circuit simulation has become a core technology for the field of electrical engineering, but its application in biology has not yet been fully realized. As a case study for evaluating the more advanced features of a circuit simulation tool called Advanced Design System (ADS), we collected and modeled laboratory data for iron metabolism in mouse kidney cells for a H ferritin (HFt) receptor, T cell immunoglobulin and mucin domain-2 (TIM-2). The internal controlling parameters of TIM-2 associated iron metabolism were extracted and the ratios of iron movement among cellular compartments were quantified by ADS. The differential model processed by circuit simulation demonstrated a capability to identify variables and predict outcomes that could not be readily measured by in vitro experiments. For example, an initial rate of uptake of iron-loaded HFt (Fe-HFt) was 2.17 pmol per million cells. TIM-2 binding probability with Fe-HFt was 16.6%. An average of 8.5 min was required for the complex of TIM-2 and Fe-HFt to form an endosome. The endosome containing HFt lasted roughly 2 h. At the end of endocytosis, about 28% HFt remained intact and the rest was degraded. Iron released from degraded HFt was in the labile iron pool (LIP) and stimulated the generation of endogenous HFt for new storage. Both experimental data and the model showed that TIM-2 was not involved in the process of iron export. The extracted internal controlling parameters successfully captured the complexity of TIM-2 pathway and the use of circuit simulation-based modeling across a wider range of cellular systems is the next step for validating the significance and utility of this method. PMID:23761763

  6. Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

    PubMed Central

    Schlachter, Eva K; Widmer, Hans Ruedi; Bregy, Amadé; Lönnfors-Weitzel, Tarja; Vajtai, Istvan; Corazza, Nadia; Bernau, Vianney JP; Weitzel, Thilo; Mordasini, Pasquale; Slotboom, Johannes; Herrmann, Gudrun; Bogni, Serge; Hofmann, Heinrich; Frenz, Martin; Reinert, Michael

    2011-01-01

    Background: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. Methods: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. Results: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 μg/mL to 25 μg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. Conclusion: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local

  7. Impaired growth under iron-limiting conditions associated with the acquisition of colistin resistance in Acinetobacter baumannii.

    PubMed

    López-Rojas, Rafael; García-Quintanilla, Meritxell; Labrador-Herrera, Gema; Pachón, Jerónimo; McConnell, Michael J

    2016-06-01

    Acquisition of colistin resistance in Acinetobacter baumannii has been associated with reduced bacterial fitness and virulence, although the mechanisms underlying this fitness loss have not been well characterised. In this study, the role played by environmental iron levels on the growth and survival of colistin-resistant strains of A. baumannii was assessed. Growth assays with the colistin-susceptible ATCC 19606 strain and its colistin-resistant derivative RC64 [colistin minimum inhibitory concentration (MIC) of 64 mg/L] demonstrated that the strains grew similarly in rich laboratory medium (Mueller-Hinton broth), whereas RC64 demonstrated impaired growth compared with ATCC 19606 in human serum (>100-fold at 24 h). Compared with RC64, ATCC 19606 grew in the presence of higher concentrations of the iron-specific chelator 2,2'-bipyridine and grew more readily under iron-limiting conditions in solid and liquid media. In addition, iron supplementation of human serum increased the growth of RC64 compared with unsupplemented human serum to a greater extent than ATCC 19606. The ability of 11 colistin-resistant clinical isolates with mutations in the pmrB gene to grow in iron-replete and iron-limiting conditions was assessed, demonstrating that eight of the strains showed reduced growth under iron limitation. Individual mutations in the pmrB gene did not directly correlate with a decreased capacity for growth under iron limitation, suggesting that mutations in pmrB may not directly produce this phenotype. Together these results indicate that acquisition of colistin resistance in A. baumannii can be associated with a decreased ability to grow in low-iron environments. PMID:27179817

  8. Determining Host Metabolic Limitations on Viral Replication via Integrated Modeling and Experimental Perturbation

    PubMed Central

    Birch, Elsa W.; Ruggero, Nicholas A.; Covert, Markus W.

    2012-01-01

    Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly. A fundamental example is the infection of Escherichia coli by bacteriophage T7. The resource draw imposed by viral replication represents a significant and complex perturbation to the extensive and interconnected network of host metabolic pathways. To better understand this system, we have integrated a set of structured ordinary differential equations quantifying T7 replication and an E. coli flux balance analysis metabolic model. Further, we present here an integrated simulation algorithm enforcing mutual constraint by the models across the entire duration of phage replication. This method enables quantitative dynamic prediction of virion production given only specification of host nutritional environment, and predictions compare favorably to experimental measurements of phage replication in multiple environments. The level of detail of our computational predictions facilitates exploration of the dynamic changes in host metabolic fluxes that result from viral resource consumption, as well as analysis of the limiting processes dictating maximum viral progeny production. For example, although it is commonly assumed that viral infection dynamics are predominantly limited by the amount of protein synthesis machinery in the host, our results suggest that in many cases metabolic limitation is at least as strict. Taken together, these results emphasize the importance of considering viral infections in the context of host metabolism. PMID:23093930

  9. Performance analysis of saturated iron core superconducting fault current limiter using Jiles-Atherton hysteresis model

    NASA Astrophysics Data System (ADS)

    Sarkar, D.; Roy, D.; Choudhury, A. B.; Yamada, S.

    2015-09-01

    In this paper study of the Saturated Iron Core Superconducting Fault Current Limiter (SISFCL) has been carried out. Since in an SISFCL, the iron core plays a key role in distributing the magnetic flux, the hysteresis property of the core material has been introduced in a mathematical model to get a more accurate result. In this paper the Jiles-Atherton hysteresis model has been used for modeling the core. The equations are solved through numerical method and performances of SISFCL are analyzed for both normal and fault conditions. On further analysis it is observed that for suppression of higher value of fault current a high voltage develops across the DC source. Hence there is a chance of the DC source being damaged by the rise in voltage under fault condition. In order to protect the DC source, a shorted ring is introduced in the SISFCL circuit and its effects have been analyzed. It is noticed that the shorted ring has successfully reduced the voltage across the DC coil during fault condition while the performance of the limiter remains the same.

  10. Iron

    MedlinePlus

    ... organ failure, coma, convulsions, and death. Child-proof packaging and warning labels on iron supplements have greatly ... levodopa that the body absorbs, making it less effective. Levodopa, found in Sinemet® and Stalevo®, is used ...

  11. Influence of lead on repetitive behavior and dopamine metabolism in a mouse model of iron overload.

    PubMed

    Chang, JuOae; Kueon, Chojin; Kim, Jonghan

    2014-12-01

    Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that

  12. Iron deficiency limits phytoplankton growth in the north-east Pacific subarctic

    NASA Astrophysics Data System (ADS)

    Martin, John H.; Fitzwater, Steve E.

    1988-01-01

    An interesting oceanographic problem concerns the excess major plant nutrients (PO4, NO3, SiO3) occurring in offshore surface waters of the Antarctic1-3 and north-east Pacific subarctic Oceans4. In a previous study5, we presented indirect evidence suggesting that inadequate Fe input was responsible for this limitation of growth; recently we had the opportunity to seek direct evidence for this hypothesis in the north-east Pacific subarctic. We report here that the addition of nmol amounts of dissolved iron resulted in the nearly complete utilization of excess NO3, whereas in the controls-without added Fe-only 25% of the available NO3 was used. We also observed that the amounts of chlorophyll in the phytoplankton increased in proportion to the Fe added. We conclude that Fe deficiency is limiting phytoplankton growth in these major-nutrient-rich waters.

  13. The implications of reduced metabolic rate in resource-limited corals.

    PubMed

    Jacobson, Lianne M; Edmunds, Peter J; Muller, Erik B; Nisbet, Roger M

    2016-03-01

    Many organisms exhibit depressed metabolism when resources are limited, a change that makes it possible to balance an energy budget. For symbiotic reef corals, daily cycles of light and periods of intense cloud cover can be chronic causes of food limitation through reduced photosynthesis. Furthermore, coral bleaching is common in present-day reefs, creating a context in which metabolic depression could have beneficial value to corals. In the present study, corals (massive Porites spp.) were exposed to an extreme case of resource limitation by starving them of food and light for 20 days. When resources were limited, the corals depressed area-normalized respiration to 37% of initial rates, and coral biomass declined to 64% of initial amounts, yet the corals continued to produce skeletal mass. However, the declines in biomass cannot account for the declines in area-normalized respiration, as mass-specific respiration declined to 30% of the first recorded time point. Thus, these corals appear to be capable of metabolic depression. It is possible that some coral species are better able to depress metabolic rates than others; such variation could explain differential survival during conditions that limit resources (e.g. shading). Furthermore, we found that maintenance of existing biomass, in part, supports the production of skeletal mass. This association could be explained if maintenance supplies needed energy (e.g. ATP) or inorganic carbon (i.e. CO2) that otherwise limits the production of skeletal mass. Finally, the observed metabolic depression can be explained as a change in pool sizes, and does not require a change in metabolic rules. PMID:26823098

  14. Molecular evidence of iron limitation and availability in the global diazotroph Trichodesmium

    PubMed Central

    Chappell, Phoebe Dreux; Moffett, James W; Hynes, Annette M; Webb, Eric A

    2012-01-01

    The activity of the N2-fixing cyanobacterial genus Trichodesmium is critical to the global nitrogen (N) and carbon (C) cycles. Although iron (Fe) has been shown to be an important element limiting the growth and N2 fixation of Trichodesmium, there have been no specific data demonstrating the in situ affect of Fe on Trichodesmium. We surveyed Trichodesmium populations from the Atlantic and Pacific Oceans for Fe limitation using a novel quantitative reverse transcriptase-PCR (qRT-PCR) method monitoring the expression of an Fe limitation-induced gene, isiB. Here we report the first molecular evidence of in situ Fe limitation of Trichodesmium N2 fixation, which was evident in samples from the Pacific Ocean, whereas limitation appeared minimal to nonexistent in Atlantic Ocean samples. As our method is Trichodesmium clade specific, we were also able to determine that representatives from the Trichodesmium tenue clade were the most biologically active group of Trichodesmium in the majority of our samples, which speaks to their dominance in open ocean regimes. Furthermore, comparisons of our field expression and chemical data with laboratory studies suggest that the majority of dissolved Fe in the open ocean is available to Trichodesmium colonies regardless of Fe complexation. PMID:22402399

  15. An update on iron physiology

    PubMed Central

    Muñoz, Manuel; Villar, Isabel; García-Erce, José Antonio

    2009-01-01

    Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia. PMID:19787824

  16. Tick iron and heme metabolism - New target for an anti-tick intervention.

    PubMed

    Hajdusek, Ondrej; Sima, Radek; Perner, Jan; Loosova, Gabriela; Harcubova, Adela; Kopacek, Petr

    2016-06-01

    Ticks are blood-feeding parasites and vectors of serious human and animal diseases. Ixodes ricinus is a common tick in Europe, transmitting tick-borne encephalitis, Lyme borreliosis, anaplasmosis, or babesiosis. Immunization of hosts with recombinant tick proteins has, in theory, the potential to interfere with tick feeding and block transmission of pathogens from the tick to the host. However, the efficacy of tick antigens has, to date, not been fully sufficient to achieve this. We have focused on 11 in silico identified genes encoding proteins potentially involved in tick iron and heme metabolism. Quantitative real-time PCR (qRT-PCR) expression profiling was carried out to preferentially target proteins that are up-regulated during the blood meal. RNA interference (RNAi) was then used to score the relative importance of these genes in tick physiology. Finally, we performed vaccination screens to test the suitability of these proteins as vaccine candidates. These newly identified tick antigens have the potential to improve the available anti-tick vaccines. PMID:26810909

  17. Iron in Infection and Immunity

    PubMed Central

    Cassat, James E.; Skaar, Eric P.

    2013-01-01

    Iron is an essential nutrient for both humans and pathogenic microbes. Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication. However, the redox potential of iron also contributes to its toxicity, thus iron concentration and distribution must be carefully controlled. Given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune system is to limit iron availability to invading microbes in a process termed nutritional immunity. Successful human pathogens must therefore possess mechanisms to circumvent nutritional immunity in order to cause disease. In this review, we discuss regulation of iron metabolism in the setting of infection and delineate strategies used by human pathogens to overcome iron-withholding defenses. PMID:23684303

  18. Genetic indicators of iron limitation in wild populations of Thalassiosira oceanica from the northeast Pacific Ocean

    PubMed Central

    Chappell, P Dreux; Whitney, LeAnn P; Wallace, Joselynn R; Darer, Adam I; Jean-Charles, Samua; Jenkins, Bethany D

    2015-01-01

    Assessing the iron (Fe) nutritional status of natural diatom populations has proven challenging as physiological and molecular responses can differ in diatoms of the same genus. We evaluated expression of genes encoding flavodoxin (FLDA1) and an Fe-starvation induced protein (ISIP3) as indicators of Fe limitation in the marine diatom Thalassiosira oceanica. The specificity of the response to Fe limitation was tested in cultures grown under Fe- and macronutrient-deficient conditions, as well as throughout the diurnal light cycle. Both genes showed a robust and specific response to Fe limitation in laboratory cultures and were detected in small volume samples collected from the northeast Pacific, demonstrating the sensitivity of this method. Overall, FLDA1 and ISIP3 expression was inversely related to Fe concentrations and offered insight into the Fe nutritional health of T. oceanica in the field. As T. oceanica is a species tolerant to low Fe, indications of Fe limitation in T. oceanica populations may serve as a proxy for severe Fe stress in the overall diatom community. At two shallow coastal locations, FLD1A and ISIP3 expression revealed Fe stress in areas where dissolved Fe concentrations were high, demonstrating that this approach may be powerful for identifying regions where Fe supply may not be biologically available. PMID:25333460

  19. Limited proteolysis of myoglobin opens channel in ferrochelatase-globin complex for iron to zinc transmetallation.

    PubMed

    Paganelli, Marcella O; Grossi, Alberto B; Dores-Silva, Paulo R; Borges, Julio C; Cardoso, Daniel R; Skibsted, Leif H

    2016-11-01

    Recombinant ferrochelatase (BsFECH) from Bacillus subtilis expressed in Escherichia coli BL21(DE3) was found by UV-visible spectroscopy to bind the model substrate tetraphenylporphyrin-sulfonate, TPPS, with Ka=3.8 10(5)mol/L in aqueous phosphate buffer pH 5.7 at 30°C, and to interact with metmyoglobin with Ka=1.07±0.13 10(5)mol/L at 30°C. The iron/zinc exchange in myoglobin occurring during maturation of Parma hams seems to depend on such substrate binding to BsFECH and was facilitated by limited pepsin proteolysis of myoglobin to open a reaction channel for metal exchange still with BsFECH associated to globin. BsFECH increased rate of zinc insertion in TPPS significantly and showed saturation kinetics with an apparent binding constant of Zn(II) to the [enzyme-TPPS] complex of 1.3 10(4)mol/L and a first-order rate constant of 6.6 10(-1)s(-1) for dissociation of the tertiary complex, a similar pattern was found for zinc/iron transmetallation in myoglobin. PMID:27211675

  20. Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: mirror-image effector molecules that target iron.

    PubMed Central

    Watts, Ralph N; Ponka, Prem; Richardson, Des R

    2003-01-01

    Many effector functions of nitrogen monoxide (NO) and carbon monoxide (CO) are mediated through their high-affinity for iron (Fe). In this review, the roles of NO and CO are examined in terms of their effects on the molecular and cellular mechanisms involved in Fe metabolism. Both NO and CO avidly form complexes with a plethora of Fe-containing molecules. The generation of NO and CO is mediated by the nitric oxide synthase and haem oxygenase (HO) families of enzymes respectively. The effects of NO on Fe metabolism have been well characterized, whereas knowledge of the effects of CO remains within its infancy. In terms of the role of NO in Fe metabolism, one of the best characterized interactions includes its effect on the iron regulatory proteins. These molecules are mRNA-binding proteins that control the expression of the transferrin receptor 1 and ferritin, molecules that are involved in Fe uptake and storage respectively. Apart from this, activated macrophages impart their cytotoxic activity by generating NO, which results in marked Fe mobilization from tumour-cell targets. This deprives the cell of the Fe that is required for DNA synthesis and energy production. Considering that HO degrades haem, resulting in the release of CO, Fe(II) and biliverdin, it is suggested that a CO-Fe complex will form. This may account for the rapid Fe mobilization observed from macrophages after haemoglobin catabolism. Intriguingly, overexpression of HO results in cellular Fe mobilization, suggesting that CO has a similar effect to NO on Fe trafficking. Preliminary evidence suggests that, like NO, CO plays important roles in Fe metabolism. PMID:12423201

  1. MBD5 regulates iron metabolism via methylation-independent genomic targeting of Fth1 through KAT2A in mice.

    PubMed

    Tao, Yunlong; Wu, Qian; Guo, Xin; Zhang, Zhuzhen; Shen, Yuanyuan; Wang, Fudi

    2014-07-01

    Ferritin plays important roles in iron metabolism and controls iron absorption in the intestine. The ferritin subunits ferritin heavy chain (Fth1) and ferritin light chain (Ftl1) are tightly regulated at both the transcriptional and post-transcriptional levels. However, mechanisms of maintaining stable, basal expression of Fth1 are poorly understood. Here, we show that global deletion of Mbd5 in mice induces an iron overload phenotype. Liver and serum iron levels in Mbd5(-/-) mice were 3·2-fold and 1·5-fold higher respectively, than wild-type littermates; moreover, serum ferritin was increased >5-fold in the Mbd5(-/-) mice. Mbd5 encodes a member of the methyl-CpG binding domain family; however, the precise function of this gene is poorly understood. Here, we found that intestinal Fth1 mRNA levels were decreased in Mbd5(-/-) mice. Loss of Fth1 expression in the intestine could lead to iron over-absorption. Furthermore, deleting Mbd5 specifically in the intestine resulted in a phenotype similar to that of conditional deletion of Fth1 mice. An Fth1 promoter-report luciferase assay indicated that overexpression of Mbd5 enhanced Fth1 transcription in a dose-dependent manner. Histone H4 acetylation of the Fth1 promoter was reduced in the intestine of Mbd5(-/-) mice and further analysis showed that histone acetyltransferase KAT2A was essential for MBD5-induced Fth1 transcription. PMID:24750026

  2. The limited streamer tubes system for the SLD warm iron calorimeter

    SciTech Connect

    Benvenuti, A.C.; Camanzi, B.; Piemontese, L.; Zucchelli, P. |; Calcaterra, A.; De Sangro, R.; De Simone, P.; De Simone, S.; Gallinaro, M.; Peruzzi, I.; Piccolo, M.; Burrows, P.N.; Busza, W.; Cartwright, S.L.; Fuess, S.; Gonzalez, S.; Hansl-Kozanecka, T.; Lath, A.; Lyons, T.; Osborne, L.S.; Rosenson, L.; Schneekloth, U.; Taylor, F.E.; Verdier, R.; Williams, D.C.; Yamartino, J.M.; Bacchetta, N.; Bisello, D.; Castro, A.; Galvagni, S.; Loreti, M.; Pescara, L.; Wyss, J. |; Battiston, R.; Biasini, M.; Bilei, G.M.; Checcucci, B; Mancinelli, G.; Mantovani, G.; Pauluzzi, M.; Santocchia, A.; Servoli, L. |; Carpinelli, M.; Castaldi, R.; Cazzola, U.; Dell`Orso, R.; Pieroni, E.; Vannini, C.; Verdini, P.G. |; Byers, B.L.; Escalera, J.; Kharakh, D.; Messner, R.L.; Zdarko, R.W.; Johnson, J.R.

    1992-01-01

    The SLD detector at the Stanford Linear Accelerator Center is a general purpose device for studying e{sup +}{epsilon}{sup {minus}} interaction at the Z{sup 0}. The SLD calorimeter system consists of two parts: a lead Liquid Argon Calorimeter (LAC) with both electromagnetic (22 radiation lengths) and hadronic sections (2.8 absorption lengths) housed inside the coil, and the Warm Ion limited streamer tubes Calorimeter (WIC) outside the coil which uses as radiator the iron of the flux return for the magnetic field. The WIC completes the measurement of the hadronic shower energy ({approximately}85% on average is contained in the LAC) and it provides identification and tracking for muons over 99% of the solid angle. In this note we report on the construction, test and commissioning of such a large system.

  3. First-pass metabolism limits the intestinal absorption of enteral alpha-ketoglutarate in young pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our results in a previous study indicated that the portal absorption of intragastrically fed alpha-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net ...

  4. Higher iron pearl millet (Pennisetum glaucum L.) provides more absorbable iron that is limited by increased polyphenolic content

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Our objective was to compare the capacity of iron (Fe) biofortified and standard pearl millet (Pennisetum glaucum L.) to deliver Fe for hemoglobin (Hb) synthesis. Pearl millet is the most widely grown type of millet. It is common primarily in West Africa and the Indian subcontinent, and ...

  5. Differential Role of Ferritins in Iron Metabolism and Virulence of the Plant-Pathogenic Bacterium Erwinia chrysanthemi 3937▿

    PubMed Central

    Boughammoura, Aïda; Matzanke, Berthold F.; Böttger, Lars; Reverchon, Sylvie; Lesuisse, Emmanuel; Expert, Dominique; Franza, Thierry

    2008-01-01

    During infection, the phytopathogenic enterobacterium Erwinia chrysanthemi has to cope with iron-limiting conditions and the production of reactive oxygen species by plant cells. Previous studies have shown that a tight control of the bacterial intracellular iron content is necessary for full virulence. The E. chrysanthemi genome possesses two loci that could be devoted to iron storage: the bfr gene, encoding a heme-containing bacterioferritin, and the ftnA gene, coding for a paradigmatic ferritin. To assess the role of these proteins in the physiology of this pathogen, we constructed ferritin-deficient mutants by reverse genetics. Unlike the bfr mutant, the ftnA mutant had increased sensitivity to iron deficiency and to redox stress conditions. Interestingly, the bfr ftnA mutant displayed an intermediate phenotype for sensitivity to these stresses. Whole-cell analysis by Mössbauer spectroscopy showed that the main iron storage protein is FtnA and that there is an increase in the ferrous iron/ferric iron ratio in the ftnA and bfr ftnA mutants. We found that ftnA gene expression is positively controlled by iron and the transcriptional repressor Fur via the small antisense RNA RyhB. bfr gene expression is induced at the stationary phase of growth. The σS transcriptional factor is necessary for this control. Pathogenicity tests showed that FtnA and the Bfr contribute differentially to the virulence of E. chrysanthemi depending on the host, indicating the importance of a perfect control of iron homeostasis in this bacterial species during infection. PMID:18165304

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptospira interrogans is the causative agent of leptospirosis, a zoonosis of global significance. Iron is essential for growth of most bacterial species. Since availability of iron is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In ...

  7. The effect of engineered iron nanoparticles on growth and metabolic status of marine microalgae cultures.

    PubMed

    Kadar, Eniko; Rooks, Paul; Lakey, Cara; White, Daniel A

    2012-11-15

    Synthetic zero-valent nano-iron (nZVI) compounds are finding numerous applications in environmental remediation owing to their high chemical reactivity and versatile catalytic properties. Studies were carried out to assess the effects of three types of industrially relevant engineered nZVI on phytoplankton growth, cellular micromorphology and metabolic status. Three marine microalgae (Pavlova lutheri, Isochrysis galbana and Tetraselmis suecica) were grown on culture medium fortified with the nano-Fe compounds for 23 days and subsequent alterations in their growth rate, size distribution, lipid profiles and cellular ultrastructure were assessed. The added nano Fe concentrations were either equimolar with the EDTA-Fe conventionally added to the generic f/2 medium (i.e. 1.17 × 10(-5)M), or factor 10 lower and higher, respectively. We provide evidence for the: (1) broad size distribution of nZVI particles when added to the nutrient rich f/2 media with the higher relative percentage of the smallest particles with the coated forms; (2) normal algal growth in the presence of all three types of nZVIs with standard growth rates, cellular morphology and lipid content comparable or improved when compared to algae grown on f/2 with EDTA-Fe; (3) sustained algal growth and normal physiology at nZVI levels 10 fold below that in f/2, indicating preference to nanoparticles over EDTA-Fe; (4) increased total cellular lipid content in T. suecica grown on media enriched with uncoated nZVI25, and in P. lutheri with inorganically coated nZVI(powder), when compared at equimolar exposures; (5) significant change in fatty acid composition complementing the nZVI(powder)-mediated increase in lipid content of P. lutheri; (6) a putative NP uptake mechanism is proposed for I. galbana via secretion of an extracellular matrix that binds nZVIs which then become bioavailable via phagocytotic membrane processes. PMID:23059967

  8. Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice.

    PubMed

    Viatte, Lydie; Lesbordes-Brion, Jeanne-Claire; Lou, Dan-Qing; Bennoun, Myriam; Nicolas, Gaël; Kahn, Axel; Canonne-Hergaux, François; Vaulont, Sophie

    2005-06-15

    Evidence is accumulating that hepcidin, a liver regulatory peptide, could be the common pathogenetic denominator of all forms of iron overload syndromes including HFE-related hemochromatosis, the most prevalent genetic disorder characterized by inappropriate iron absorption. To understand the mechanisms whereby hepcidin controls iron homeostasis in vivo, we have analyzed the level of iron-related proteins by Western blot and immunohistochemistry in hepcidin-deficient mice, a mouse model of severe hemochromatosis. These mice showed important increased levels of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), and ferroportin compared with control mice. Interestingly, the level of ferroportin was coordinately up-regulated in the duodenum, the spleen, and the liver (predominantly in the Kupffer cells). Finally, we also evidenced a decrease of ceruloplasmin in the liver of hepcidin-deficient mice. We hypothesized that the deregulation of these proteins might be central in the pathogenesis of iron overload, providing key therapeutic targets for iron disorders. PMID:15713792

  9. The heme-p53 interaction: Linking iron metabolism to p53 signaling and tumorigenesis.

    PubMed

    Shen, Jia; Sheng, Xiangpeng; Chang, ZeNan; Wu, Qian; Xie, Dong; Wang, Fudi; Hu, Ronggui

    2016-01-01

    Recently, we reported that heme binds to tumor suppressor p53 protein (TP53, best known as p53) and promotes its nuclear export and cytosolic degradation, whereas iron chelation stabilizes p53 protein and suppresses tumors in a p53-dependent manner. This not only provides mechanistic insights into tumorigenesis associated with iron excess, but also helps guide the administration of chemotherapy based on iron deprivation in the clinic. PMID:27308524

  10. The heme–p53 interaction: Linking iron metabolism to p53 signaling and tumorigenesis

    PubMed Central

    Shen, Jia; Sheng, Xiangpeng; Chang, ZeNan; Wu, Qian; Xie, Dong; Wang, Fudi; Hu, Ronggui

    2016-01-01

    Recently, we reported that heme binds to tumor suppressor p53 protein (TP53, best known as p53) and promotes its nuclear export and cytosolic degradation, whereas iron chelation stabilizes p53 protein and suppresses tumors in a p53-dependent manner. This not only provides mechanistic insights into tumorigenesis associated with iron excess, but also helps guide the administration of chemotherapy based on iron deprivation in the clinic. PMID:27308524

  11. Volume dependence of the Grüneisen parameter and maximum compression limit for iron

    NASA Astrophysics Data System (ADS)

    Shanker, J.; Singh, B. P.; Baghel, H. K.

    2007-01-01

    Relationships for the volume dependence of the Grüneisen parameter γ have been used to discuss the behaviour of solids in the limit of infinite pressure ( P→∞). The model recently developed by Burakovsky and Preston (J. Phys. Chem. Solids 65 (2004) 1581) yields γ∞, q∞ and λ∞, the values of Grüneisen parameter γ and its logarithmic volume derivatives q and λ at P→∞, which are found to have fixed values, same for all the solids studied. On the other hand, the thermodynamics of solids at P→∞ formulated by Stacey (Geophys. J. Int. 143 (2000) 621) reveals that γ∞ and pressure derivative of bulk modulus are different for different materials. The empirical formulation for the volume dependence of γ used by Stacey and Davis (Phys. Earth Planet. Intr. 142 (2004) 137) has been shown to be approximately equivalent to the relationship proposed earlier by Al’tshuler et al. (J. Appl. Mech. Tech. Phys. 28 (1987) 129). The shock-pressure data for iron have been used to discuss the maximum compression limit for iron and to emphasize the invalidity of our recent criterion based on the lattice potential energy (Physica B 364 (2005) 186). The Burakovsky-Preston model based on the Thomas-Fermi approximation ( γ∞=1/2 and =5/3) has been found to be more consistent with the shock-compression data. The constraints γ∞>2/3 and >5/3 developed by Stacey are not in agreement with the strong shock compression limit reported for several materials. It is shown here that the Slater formula for γ which was found by Stacey to assume the status of an identity at P→∞ and used by him to derive the constraints for γ∞ and , is invalid when =5/3 It is also pointed out that γ∞=1/2 is to be preferred over γ∞=2/3 because of the thermodynamic constraint >1+ γ∞ developed by Stacey.

  12. Structure-substitution limit correlation study on Cr3+ substituted polycrystalline yttrium iron garnet

    NASA Astrophysics Data System (ADS)

    Modi, K. B.; Sharma, P. U.; Lakhani, V. K.; Vasoya, N. H.; Saija, K. G.; Pathak, T. K.; Zankat, K. B.

    2016-05-01

    Polycrystalline samples of Cr3+ - substituted yttrium iron garnet (Y3Fe5O12) system with general chemical formula, Y3Fe5-xCrxO12, x = 0.0, 0.2, 0.4 and 0.6 were synthesized by double sintering ceramic technique and characterized by X-ray powder diffractometry. The Rietveld fitted X-ray diffraction patterns analysis revealed mono phase formation for x = 0.0 - 0.4 compositions while x = 0.6 composition possesses mixed phase character. The observed substitution limit has been discussed in the light of ionic size of substituent, electrostatic energy, electronic configuration and synthesis parameters. These observations strongly suggest that the electronic configuration of Cr3+, which is favorable to the formation of d2sp3 (octahedral) type bonds, must be important. In the case of Cr3+, the substitution does not appear to proceed well for x much greater than 0.5, this limitation probably is a consequence of the strong preference of a smaller ion Cr3+, for a larger octahedral site which quickly leads to a condition not comparable with the requirement of the structure. The distribution of cations, mean ionic radii and theoretical lattice constant values have been determined.

  13. Relation between iron metabolism and antioxidants enzymes and δ-ALA-D activity in rats experimentally infected by Fasciola hepatica.

    PubMed

    Bottari, Nathieli B; Mendes, Ricardo E; Baldissera, Matheus D; Bochi, Guilherme V; Moresco, Rafael N; Leal, Marta L R; Morsch, Vera M; Schetinger, Maria R C; Christ, Ricardo; Gheller, Larissa; Marques, Éder J; Da Silva, Aleksandro S

    2016-06-01

    The aim of this study was to evaluate the iron metabolism in serum, as well as antioxidant enzymes, in addition to the Delta-Aminolevulinic Acid Dehydratase (δ-ALA-D) activity in the liver of rats experimentally infected by Fasciola hepatica. Thirty male adult rats (Wistar) specific pathogen free were divided into four groups: two uninfected group (CTRL 1 and CTRL 2) with five animals each and two infected groups (INF 1 and INF 2) with 10 animals each. Infection was performed orally with 20 metacercariae at day 1. On day 15 (CTRL 1 and INF 1 groups) and 87 PI (CTRL 2 and INF 2 groups) blood and bone marrow were collected and the animals were subsequently euthanized for liver sampling. Blood was allocated in tubes without anticoagulant for serum acquisition to measure iron, transferrin and unsaturated iron binding capacity (UIBC). δ-ALA-D, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the liver. A decrease in iron, transferrin and UIBC levels was observed in all infected animals compared to control groups (P < 0.05). Furthermore, iron accumulation was observed in bone marrow of infected mice. Infected animals showed an increase in δ-ALA-D activity at 87 post-infection (PI) (INF 2) as well as in SOD activity at days 15 (INF 1) and 87 PI (INF 2). On the other hand, CAT activity was reduced in rats infected by F. hepatica during acute and chronic phase of fasciolosis (INF 1 and INF 2 groups), when moderate (acute) and severe necrosis in the liver histopathology were observed. These results may suggest that oxidative damage to tissues along with antioxidant mechanisms might have taken part in fasciolosis pathogenesis and are also involved in iron deficiency associated to changes in δ-ALA-D activity during chronic phase of disease. PMID:26995536

  14. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    NASA Astrophysics Data System (ADS)

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  15. Responses to iron limitation are impacted by light quality and regulated by RcaE in the chromatically acclimating cyanobacterium Fremyella diplosiphon.

    PubMed

    Pattanaik, Bagmi; Busch, Andrea W U; Hu, Pingsha; Chen, Jin; Montgomery, Beronda L

    2014-05-01

    Photosynthetic organisms adapt to environmental fluctuations of light and nutrient availability. Iron is critical for photosynthetic organismal growth, as many cellular processes depend upon iron cofactors. Whereas low iron levels can have deleterious effects, excess iron can lead to damage, as iron is a reactive metal that can result in the production of damaging radicals. Therefore, organisms regulate cellular iron levels to maintain optimal iron homeostasis. In particular, iron is an essential factor for the function of photosystems associated with photosynthetic light-harvesting complexes. Photosynthetic organisms, including cyanobacteria, generally respond to iron deficiency by reduced growth, degradation of non-essential proteins and in some cases alterations of cellular morphology. In response to fluctuations in ambient light quality, the cyanobacterium Fremyella diplosiphon undergoes complementary chromatic adaptation (CCA). During CCA, phycobiliprotein composition of light-harvesting antennae is altered in response to green light (GL) and red light (RL) for efficient utilization of light energy for photosynthesis. We observed light-regulated responses to iron limitation in F. diplosiphon. RL-grown cells exhibited significant reductions in growth and pigment levels, and alterations in iron-associated proteins, which impact the accumulation of reactive oxygen species under iron-limiting conditions, whereas GL-grown cells exhibited partial resistance to iron limitation. We investigated the roles of known CCA regulators RcaE, RcaF and RcaC in this light-dependent iron-acclimation response. Through comparative analyses of wild-type and CCA mutant strains, we determined that photoreceptor RcaE has a central role in light-induced oxidative stress associated with iron limitation, and impacts light-regulated iron-acclimation responses, physiologically and morphologically. PMID:24623652

  16. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo.

    PubMed

    Moroishi, Toshiro; Nishiyama, Masaaki; Takeda, Yukiko; Iwai, Kazuhiro; Nakayama, Keiichi I

    2011-09-01

    Iron-dependent degradation of iron-regulatory protein 2 (IRP2) is a key event for maintenance of an appropriate intracellular concentration of iron. Although FBXL5 (F box and leucine-rich repeat protein 5) is thought to mediate this degradation, the role of FBXL5 in the control of iron homeostasis in vivo has been poorly understood. We have now found that mice deficient in FBXL5 died in utero, associated with excessive iron accumulation. This embryonic mortality was prevented by additional ablation of IRP2, suggesting that impaired IRP2 degradation is primarily responsible for the death of Fbxl5(-)(/-) mice. We also found that liver-specific deletion of Fbxl5 resulted in deregulation of both hepatic and systemic iron homeostasis, leading to the development of steatohepatitis. The liver-specific mutant mice died with acute liver failure when fed a high-iron diet. Thus, our results uncover a major role for FBXL5 in ensuring an appropriate supply of iron to cells. PMID:21907140

  17. Iron Limitation Modulates Ocean Acidification Effects on Southern Ocean Phytoplankton Communities

    PubMed Central

    Hoppe, Clara J. M.; Hassler, Christel S.; Payne, Christopher D.; Tortell, Philippe D.; Rost, Björn; Trimborn, Scarlett

    2013-01-01

    The potential interactive effects of iron (Fe) limitation and Ocean Acidification in the Southern Ocean (SO) are largely unknown. Here we present results of a long-term incubation experiment investigating the combined effects of CO2 and Fe availability on natural phytoplankton assemblages from the Weddell Sea, Antarctica. Active Chl a fluorescence measurements revealed that we successfully cultured phytoplankton under both Fe-depleted and Fe-enriched conditions. Fe treatments had significant effects on photosynthetic efficiency (Fv/Fm; 0.3 for Fe-depleted and 0.5 for Fe-enriched conditions), non-photochemical quenching (NPQ), and relative electron transport rates (rETR). pCO2 treatments significantly affected NPQ and rETR, but had no effect on Fv/Fm. Under Fe limitation, increased pCO2 had no influence on C fixation whereas under Fe enrichment, primary production increased with increasing pCO2 levels. These CO2-dependent changes in productivity under Fe-enriched conditions were accompanied by a pronounced taxonomic shift from weakly to heavily silicified diatoms (i.e. from Pseudo-nitzschia sp. to Fragilariopsis sp.). Under Fe-depleted conditions, this functional shift was absent and thinly silicified species dominated all pCO2 treatments (Pseudo-nitzschia sp. and Synedropsis sp. for low and high pCO2, respectively). Our results suggest that Ocean Acidification could increase primary productivity and the abundance of heavily silicified, fast sinking diatoms in Fe-enriched areas, both potentially leading to a stimulation of the biological pump. Over much of the SO, however, Fe limitation could restrict this possible CO2 fertilization effect. PMID:24278207

  18. Iron Metabolism Dysregulation and Cognitive Dysfunction in Pediatric Obesity: Is There a Connection?

    PubMed Central

    Grandone, Anna; Marzuillo, Pierluigi; Perrone, Laura; Miraglia del Giudice, Emanuele

    2015-01-01

    Obesity and iron deficiency (ID) are two of the most common nutritional disorders in the world. In children both conditions deserve particular attention. Several studies revealed an association between obesity and iron deficiency in children and, in some cases, a reduced response to oral supplementation. The connecting mechanism, however, is not completely known. This review is focused on: (1) iron deficiency in obese children and the role of hepcidin in the connection between body fat and poor iron status; (2) iron status and consequences on health, in particular on cognitive function; (3) cognitive function and obesity; (4) suggestion of a possible link between cognitive dysfunction and ID in pediatric obesity; and implications for therapy and future research. PMID:26561830

  19. Iron as a Cofactor That Limits the Promotion of Cyanobacteria in Lakes Across a Tropic Gradient

    NASA Astrophysics Data System (ADS)

    Sorichetti, R. J.; Creed, I. F.; Trick, C. G.

    2014-12-01

    The frequency and intensity of cyanobacterial blooms (cyanoblooms) is increasing globally. While cyanoblooms in eutrophic (nutrient-rich) freshwater lakes are expected to persist and worsen with climate change projections, many of the "new" cyanobloom reports pertain to oligotrophic (nutrient-poor) freshwater lakes with no prior history of cyanobloom occurrence. Under the pressures of a changing climate, there exists a critical research need to revisit existing conceptual models and identify cyanobloom regulating factors currently unaccounted for. Iron (Fe) is required in nearly all pathways of cyanobacterial macronutrient use, though its precise role in regulating cyanobacterial biomass across the lake trophic gradient is not fully understood. The hypotheses tested were: (1) cyanobacteria will predominate in lakes when bioavailable Fe concentration is low, and (2) cyanobacteria overcome this Fe limitation in all lakes using the siderophore-based Fe acquisition strategy to scavenge Fe providing a competitive advantage over other phytoplankton. These hypotheses were tested using natural lakes across an oligo-meso-eutrophic gradient across Canada. In all lakes sampled, the relative cyanobacterial biomass was highest at low predicted Fe bioavailability (< 1.0 × 10-19 mol L-1). Within this range of low bioavailable Fe, iron-binding organic ligands were measured. Concentrations of ligands with reactive hydroxamate moieties were positively correlated to cyanobacterial biomass in both the oligotrophic (r2 = 0.77, p < 0.001) and eutrophic (r2 = 0.81, p < 0.001) lakes suggesting a possible low-Fe mediated cellular origin, siderophores. Fe-binding ligands with catecholate-type binding sites were detected in all lakes, although lack of a relationship with cyanobacterial biomass and a significant relationship with dissolved organic carbon (DOC) in oligotrophic (r2 = 0.65, p < 0.001) and eutrophic (r2 = 0.65, p < 0.001) lakes may indicate an allochthonous source that is not

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

    PubMed

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

    2011-06-01

    In Pseudomonas aeruginosa the response to oxidative stress is orchestrated by the LysR regulator OxyR by activation of the transcription of two catalase genes (katA and katB), of the alkyl-hydroxyperoxidases ahpCF and ahpB. Next to the expected high sensitivity to oxidative stress generated by reactive oxygen species (ROS: H(2)O(2), O(2)(-)), the oxyR mutant shows a defective growth under conditions of iron limitation (Vinckx et al. 2008). Although production and uptake of the siderophore pyoverdine is not affected by the absence of oxyR, the mutant is unable to satisfy its need for iron when grown under iron limiting conditions. In order to get a better insight into the effects caused by iron limitation on the physiological response of the oxyR mutant we decided to compare the proteomes of the wild type and the mutant grown in the iron-poor casamino acids medium (CAA), in CAA plus H(2)O(2), and in CAA plus the strong iron chelator ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) (EDDHA). Especially in the presence of hydrogen peroxide the oxyR cells increase the production of stress proteins (Dps and IbpA). The superoxide dismutase SodM is produced in higher amounts in the oxyR mutant grown in CAA plus H(2)O(2). The PchB protein, a isochorismate-pyruvate lyase involved in the siderophore pyochelin biosynthesis is not detectable in the extracts from the oxyR mutant grown in the presence of hydrogen peroxide. When cells were grown in the presence of EDDHA, we observed a reduction of the ferric uptake regulator (Fur), and an increase in the two subunits of the succinyl-CoA synthetase and the fumarase FumC1. PMID:21207115

  1. Influence of Iron Chlorosis on Pigment and Protein Metabolism in Leaves of Nicotiana tabacum L. 1

    PubMed Central

    Shetty, A. S.; Miller, G. W.

    1966-01-01

    Experiments were conducted on Nicotiana tabacum, L. to study the relation in the grana among chlorophylls, carotenoids, and proteins. The effect of iron chlorosis on protein and pigment synthesis was studied at different stages of chlorosis using glycine-U-C14. Pigments were separated by thin layer chromatography. Chlorophyll a, chlorophyll b, carotenoid, and protein contents of chloroplasts from chlorotic tissue were less than those of normal tissues. A 25% decrease in protein labeling and a 45% decrease in chlorophyll labeling was noted in deficient tissue compared to normal tissue even before chlorosis was perceptible. Both normal and iron deficient leaf discs which received iron in the incubation medium incorporated higher amounts of radioactive glycine into chlorophyll a and chlorophyll b at all stages of development than their respective counterparts not supplied with iron in the incubation medium. The presence of iron in the incubation medium reduced the amount of glycine incorporated into carotenes and xanthophylls, except where the tissue was severely chlorotic. This may be attributed to active competition for glycine between the iron-dependent- (chlorophyll) and iron-independent-(carotenoid) biosynthetic pathways. Incorporation of glycine into chloroplast pigments was lowest at severe chlorosis, probably due to a reduction in the overall enzyme activity. PMID:16656270

  2. Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum

    PubMed Central

    Bozzaro, Salvatore; Buracco, Simona; Peracino, Barbara

    2013-01-01

    Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other “iron genes” will help identify genes essential for iron homeostasis and resistance to pathogens. PMID

  3. Divergent responses of Atlantic coastal and oceanic Synechococcus to iron limitation.

    PubMed

    Mackey, Katherine R M; Post, Anton F; McIlvin, Matthew R; Cutter, Gregory A; John, Seth G; Saito, Mak A

    2015-08-11

    Marine Synechococcus are some of the most diverse and ubiquitous phytoplankton, and iron (Fe) is an essential micronutrient that limits productivity in many parts of the ocean. To investigate how coastal and oceanic Atlantic Synechococcus strains acclimate to Fe availability, we compared the growth, photophysiology, and quantitative proteomics of two Synechococcus strains from different Fe regimes. Synechococcus strain WH8102, from a region in the southern Sargasso Sea that receives substantial dust deposition, showed impaired growth and photophysiology as Fe declined, yet used few acclimation responses. Coastal WH8020, from the dynamic, seasonally variable New England shelf, displayed a multitiered, hierarchical cascade of acclimation responses with different Fe thresholds. The multitiered response included changes in Fe acquisition, storage, and photosynthetic proteins, substitution of flavodoxin for ferredoxin, and modified photophysiology, all while maintaining remarkably stable growth rates over a range of Fe concentrations. Modulation of two distinct ferric uptake regulator (Fur) proteins that coincided with the multitiered proteome response was found, implying the coastal strain has different regulatory threshold responses to low Fe availability. Low nitrogen (N) and phosphorus (P) availability in the open ocean may favor the loss of Fe response genes when Fe availability is consistent over time, whereas these genes are retained in dynamic environments where Fe availability fluctuates and N and P are more abundant. PMID:26216989

  4. Associations of iron metabolism genes with blood manganese levels: a population-based study with validation data from animal models

    PubMed Central

    2011-01-01

    Background Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. Methods Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. Results Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) μg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe-/- mice displayed a significant reduction in blood manganese compared with Hfe+/+ mice, replicating the altered manganese metabolism found in our human research. Conclusions Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements. PMID:22074419

  5. Sequestration efficiency in the iron-limited North Atlantic: Implications for iron supply mode to fertilized blooms

    NASA Astrophysics Data System (ADS)

    Le Moigne, Frédéric A. C.; Moore, C. Mark; Sanders, Richard J.; Villa-Alfageme, Maria; Steigenberger, Sebastian; Achterberg, Eric P.

    2014-07-01

    Estimates of the amount of carbon sequestered in the ocean interior per unit iron (Fe) supplied, as quantified by the sequestration efficiency (Ceffx), vary widely. Such variability in Ceffx has frequently been attributed to estimate uncertainty rather than intrinsic variability. Here we derive new estimates of Ceffx for the subpolar North Atlantic, where Fe stressed conditions have recently been demonstrated. Derived values of Ceffx from across the region, including areas subject to atypical external Fe fertilization events during the year of sample collection (2010), ranged from 17 to 19 kmol C (mol Fe-1). Comparing these estimates with values from other systems, considered in the context of variable bloom durations in the different oceanographic settings, we suggest that apparent variability in Ceffx may be related to the mode of Fe delivery.

  6. The Metabolic Status Drives Acclimation of Iron Deficiency Responses in Chlamydomonas reinhardtii as Revealed by Proteomics Based Hierarchical Clustering and Reverse Genetics*

    PubMed Central

    Höhner, Ricarda; Barth, Johannes; Magneschi, Leonardo; Jaeger, Daniel; Niehues, Anna; Bald, Till; Grossman, Arthur; Fufezan, Christian; Hippler, Michael

    2013-01-01

    Iron is a crucial cofactor in numerous redox-active proteins operating in bioenergetic pathways including respiration and photosynthesis. Cellular iron management is essential to sustain sufficient energy production and minimize oxidative stress. To produce energy for cell growth, the green alga Chlamydomonas reinhardtii possesses the metabolic flexibility to use light and/or carbon sources such as acetate. To investigate the interplay between the iron-deficiency response and growth requirements under distinct trophic conditions, we took a quantitative proteomics approach coupled to innovative hierarchical clustering using different “distance-linkage combinations” and random noise injection. Protein co-expression analyses of the combined data sets revealed insights into cellular responses governing acclimation to iron deprivation and regulation associated with photosynthesis dependent growth. Photoautotrophic growth requirements as well as the iron deficiency induced specific metabolic enzymes and stress related proteins, and yet differences in the set of induced enzymes, proteases, and redox-related polypeptides were evident, implying the establishment of distinct response networks under the different conditions. Moreover, our data clearly support the notion that the iron deficiency response includes a hierarchy for iron allocation within organelles in C. reinhardtii. Importantly, deletion of a bifunctional alcohol and acetaldehyde dehydrogenase (ADH1), which is induced under low iron based on the proteomic data, attenuates the remodeling of the photosynthetic machinery in response to iron deficiency, and at the same time stimulates expression of stress-related proteins such as NDA2, LHCSR3, and PGRL1. This finding provides evidence that the coordinated regulation of bioenergetics pathways and iron deficiency response is sensitive to the cellular and chloroplast metabolic and/or redox status, consistent with systems approach data. PMID:23820728

  7. Dynamic responses of reserve carbohydrate metabolism under carbon and nitrogen limitations in Saccharomyces cerevisiae.

    PubMed

    Parrou, J L; Enjalbert, B; Plourde, L; Bauche, A; Gonzalez, B; François, J

    1999-02-01

    The dynamic responses of reserve carbohydrates with respect to shortage of either carbon or nitrogen source was studied to obtain a sound basis for further investigations devoted to the characterization of mechanisms by which the yeast Saccharomyces cerevisiae can cope with nutrient limitation during growth. This study was carried out in well-controlled bioreactors which allow accurate monitoring of growth and frequent sampling without disturbing the culture. Under glucose limitation, genes involved in glycogen and trehalose biosynthesis (GLG1, GSY1, GSY2, GAC1, GLC3, TPS1), in their degradation (GPH1, NTHI), and the typical stress-responsive CTT1 gene were coordinately induced in parallel with glycogen, when the growth has left the pure exponential phase and while glucose was still plentiful in the medium. Trehalose accumulation was delayed until the diauxic shift, although TPS1 was induced much earlier, due to hydrolysis of trehalose by high trehalase activity. In contrast, under nitrogen limitation, both glycogen and trehalose began to accumulate at the precise time when the nitrogen source was exhausted from the medium, coincidentally with the transcriptional activation of genes involved in their metabolism. While this response to nitrogen starvation was likely mediated by the stress-responsive elements (STREs) in the promoter of these genes, we found that these elements were not responsible for the co-induction of genes involved in reserve carbohydrate metabolism during glucose limitation, since GLG1, which does not contain any STRE, was coordinately induced with GSY2 and TPS1. PMID:10077186

  8. Bile Salts Affect Expression of Escherichia coli O157:H7 Genes for Virulence and Iron Acquisition, and Promote Growth under Iron Limiting Conditions

    PubMed Central

    Hamner, Steve; McInnerney, Kate; Williamson, Kerry; Franklin, Michael J.; Ford, Timothy E.

    2013-01-01

    Bile salts exhibit potent antibacterial properties, acting as detergents to disrupt cell membranes and as DNA-damaging agents. Although bacteria inhabiting the intestinal tract are able to resist bile’s antimicrobial effects, relatively little is known about how bile influences virulence of enteric pathogens. Escherichia coli O157:H7 is an important pathogen of humans, capable of causing severe diarrhea and more serious sequelae. In this study, the transcriptome response of E. coli O157:H7 to bile was determined. Bile exposure induced significant changes in mRNA levels of genes related to virulence potential, including a reduction of mRNA for the 41 genes making up the locus of enterocyte effacement (LEE) pathogenicity island. Bile treatment had an unusual effect on mRNA levels for the entire flagella-chemotaxis regulon, resulting in two- to four-fold increases in mRNA levels for genes associated with the flagella hook-basal body structure, but a two-fold decrease for “late” flagella genes associated with the flagella filament, stator motor, and chemotaxis. Bile salts also caused increased mRNA levels for seventeen genes associated with iron scavenging and metabolism, and counteracted the inhibitory effect of the iron chelating agent 2,2’-dipyridyl on growth of E. coli O157:H7. These findings suggest that E. coli O157:H7 may use bile as an environmental signal to adapt to changing conditions associated with the small intestine, including adaptation to an iron-scarce environment. PMID:24058617

  9. Iron limitation and the gamma interferon-mediated antihistoplasma state of murine macrophages.

    PubMed Central

    Lane, T E; Wu-Hsieh, B A; Howard, D H

    1991-01-01

    The zoopathogenic fungus Histoplasma capsulatum requires iron for growth. Intracellular growth of the fungus within mouse peritoneal macrophages is inhibited by recombinant murine gamma interferon (IFN-gamma). Such treatment of mouse peritoneal macrophages induces a marked downshift in transferrin receptors. We tested whether the antihistoplasma effect of IFN-gamma-treated macrophages is the result of iron deprivation. Treatment of mouse peritoneal macrophages with the intracellular iron chelator deferoxamine inhibits the intracellular growth of H. capsulatum. Exposure of macrophages to holotransferrin antagonizes the effect of both recombinant murine IFN-gamma and deferoxamine treatments. These results suggest that iron restriction may be one of the bases for the IFN-gamma-induced antihistoplasma effect of mouse macrophages. PMID:1904840

  10. Responses to iron limitation in Hordeum vulgare L. as affected by the atmospheric CO2 concentration.

    PubMed

    Haase, S; Rothe, A; Kania, A; Wasaki, J; Römheld, V; Engels, C; Kandeler, E; Neumann, G

    2008-01-01

    Elevated atmospheric CO2 treatments stimulated biomass production in Fe-sufficient and Fe-deficient barley plants, both in hydroponics and in soil culture. Root/shoot biomass ratio was increased in severely Fe-deficient plants grown in hydroponics but not under moderate Fe limitation in soil culture. Significantly increased biomass production in high CO2 treatments, even under severe Fe deficiency in hydroponic culture, indicates an improved internal Fe utilization. Iron deficiency-induced secretion of PS in 0.5 to 2.5 cm sub-apical root zones was increased by 74% in response to elevated CO2 treatments of barley plants in hydroponics but no PS were detectable in root exudates collected from soil-grown plants. This may be attributed to suppression of PS release by internal Fe concentrations above the critical level for Fe deficiency, determined at final harvest for soil-grown barley plants, even without additional Fe supply. However, extremely low concentrations of easily plant-available Fe in the investigated soil and low Fe seed reserves suggest a contribution of PS-mediated Fe mobilization from sparingly soluble Fe sources to Fe acquisition of the soil-grown barley plants during the preceding culture period. Higher Fe contents in shoots (+52%) of plants grown in soil culture without Fe supply under elevated atmospheric CO2 concentrations may indicate an increased efficiency for Fe acquisition. No significant influence on diversity and function of rhizosphere-bacterial communities was detectable in the outer rhizosphere soil (0-3 mm distance from the root surface) by DGGE of 16S rRNA gene fragments and analysis of marker enzyme activities for C-, N-, and P-cycles. PMID:18453445

  11. Acidithiobacillus ferriphilus sp. nov., a facultatively anaerobic iron- and sulfur-metabolizing extreme acidophile.

    PubMed

    Falagán, Carmen; Johnson, D Barrie

    2016-01-01

    The genus Acidithiobacillus includes three species that conserve energy from the oxidation of ferrous iron, as well as reduced sulfur, to support their growth. Previous work, based on multi-locus sequence analysis, identified a fourth group of iron- and sulfur-oxidizing acidithiobacilli as a potential distinct species. Eleven strains of 'Group IV' acidithiobacilli, isolated from different global locations, have been studied. These were all shown to be obligate chemolithotrophs, growing aerobically by coupling the oxidation of ferrous iron or reduced sulfur (but not hydrogen) to molecular oxygen, or anaerobically by the oxidation of reduced sulfur coupled to ferric iron reduction. All strains were mesophilic, although some were also psychrotolerant. Strain variation was also noted in terms of tolerance to extremely low pH and to elevated concentrations of transition metals. One strain was noted to display far greater tolerance to chloride than reported for other iron-oxidizing acidithiobacilli. All of the strains were able to catalyse the oxidative dissolution of pyrite and, on the basis of some of the combined traits of some of the strains examined, it is proposed that these may have niche roles in commercial mineral bioprocessing operations, such as for low temperature bioleaching of polysulfide ores in brackish waters. The name Acidithiobacillus ferriphilus sp. nov. is proposed to accommodate the strains described, with the type strain being M20T ( = DSM 100412T = JCM 30830T). PMID:26498321

  12. Physiological characterization of xylose metabolism in Aspergillus niger under oxygen-limited conditions.

    PubMed

    Meijer, S; Panagiotou, G; Olsson, L; Nielsen, J

    2007-10-01

    The physiology of Aspergillus niger was studied under different aeration conditions. Five different aeration rates were investigated in batch cultivations of A. niger grown on xylose. Biomass, intra- and extra-cellular metabolites profiles were determined and ten different enzyme activities in the central carbon metabolism were assessed. The focus was on organic acid production with a special interest in succinate production. The fermentations revealed that oxygen limitation significantly changes the physiology of the micro-organism. Changes in extra cellular metabolite profiles were observed, that is, there was a drastic increase in polyol production (erythritol, xylitol, glycerol, arabitol, and mannitol) and to a lesser extent in the production of reduced acids (malate and succinate). The intracellular metabolite profiles indicated changes in fluxes, since several primary metabolites, like the intermediates of the TCA cycle accumulated during oxygen limitation (on average three fold increase). Also the enzyme activities showed changes between the exponential growth phase and the oxygen limitation phase. In general, the oxygen availability has a significant impact on the physiology of this fungus causing dramatic alterations in the central carbon metabolism that should be taken into account in the design of A. niger as a succinate cell factory. PMID:17335061

  13. Changes in metabolic profile, iron and ferritin levels during the treatment of metastatic renal cancer - A new potential biomarker?

    PubMed

    Golčić, Marin; Petković, Marija

    2016-09-01

    Metastatic renal cell carcinoma (mRCC) develops in approximately 33% of all renal cancer patients. First line treatment of mRCC includes drugs such as sunitinib, temsirolimus and pazopanib, with overall survival now reaching up to 43,6months in patients with favorable-risk metastatic disease. Several side-effects in mRCC treatment, such as hypothyroidism, can be used as positive prognostic factors and indicate good response to therapy. Hypercholesterolemia and hypertriglyceridemia independent of hypothyroidism are reported as side-effects in temsirolimus treatment and recently in sunitinib treatment, but the exact mechanism and significance of the changes remains elusive. Most likely, metabolic changes are caused by inhibition of mechanistic target of rapamycin (mTOR), a positive target of tumor growth suppression, but also a regulator of iron homeostasis. There are no clinical studies reporting changes in iron and ferritin levels during mRCC biotherapy, but we hypothesize that inhibition of mTOR will also affect iron and ferritin levels. If both lipid and iron changes correlate, there is a high possibility that both changes are primarily caused by mTOR inhibition and the level of change should correlate with the inhibition of mTOR pathway and hence the efficacy of targeted treatment. We lastly hypothesize that mRCC biotherapy causes hypercholesterolemia with a possibly improved cholesterol profile due to increase HDL/LDL ratio, so statins might not have a role as supplementary treatment, whereas a sharp rise in triglyceride levels seems to be the primary target for additional therapy. PMID:27515221

  14. Iron dextran increases hepatic oxidative stress and alters expression of genes related to lipid metabolism contributing to hyperlipidaemia in murine model.

    PubMed

    Silva, Maísa; da Costa Guerra, Joyce Ferreira; Sampaio, Ana Flávia Santos; de Lima, Wanderson Geraldo; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia

    2015-01-01

    The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S), which was fed the AIN-93M diet, and the standard plus iron group (SI), which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress. PMID:25685776

  15. Iron Dextran Increases Hepatic Oxidative Stress and Alters Expression of Genes Related to Lipid Metabolism Contributing to Hyperlipidaemia in Murine Model

    PubMed Central

    Silva, Maísa; Guerra, Joyce Ferreira da Costa; Sampaio, Ana Flávia Santos; de Lima, Wanderson Geraldo; Silva, Marcelo Eustáquio

    2015-01-01

    The objective of this study was to investigate the effects of iron dextran on lipid metabolism and to determine the involvement of oxidative stress. Fischer rats were divided into two groups: the standard group (S), which was fed the AIN-93M diet, and the standard plus iron group (SI), which was fed the same diet but also received iron dextran injections. Serum cholesterol and triacylglycerol levels were higher in the SI group than in the S group. Iron dextran was associated with decreased mRNA levels of pparα, and its downstream gene cpt1a, which is involved in lipid oxidation. Iron dextran also increased mRNA levels of apoB-100, MTP, and L-FABP indicating alterations in lipid secretion. Carbonyl protein and TBARS were consistently higher in the liver of the iron-treated rats. Moreover, a significant positive correlation was found between oxidative stress products, lfabp expression, and iron stores. In addition, a negative correlation was found between pparα expression, TBARS, carbonyl protein, and iron stores. In conclusion, our results suggest that the increase observed in the transport of lipids in the bloodstream and the decreased fatty acid oxidation in rats, which was promoted by iron dextran, might be attributed to increased oxidative stress. PMID:25685776

  16. Crassulacean acid metabolism under severe light limitation: a matter of plasticity in the shadows?

    PubMed

    Ceusters, Johan; Borland, Anne M; Godts, Christof; Londers, Elsje; Croonenborghs, Sarah; Van Goethem, Davina; De Proft, Maurice P

    2011-01-01

    Despite the increased energetic costs of CAM compared with C(3) photosynthesis, it is hypothesized that the inherent photosynthetic plasticity of CAM allows successful acclimation to light-limiting conditions. The present work sought to determine if CAM presented any constraints to short and longer term acclimation to light limitation and to establish if and how metabolic and photosynthetic plasticity in the deployment of the four phases of CAM might facilitate acclimation to conditions of deep shade. Measurements of leaf gas exchange, organic acids, starch and soluble sugar (glucose, fructose, and sucrose) contents were made in the leaves of the constitutive CAM bromeliad Aechmea 'Maya' over a three month period under severe light limitation. A. 'Maya' was not particularly tolerant of severe light limitation in the short term. A complete absence of net CO(2) uptake and fluctuations in key metabolites (i.e. malate, starch or soluble sugars) indicated a dampened metabolism whilst cell death in the most photosynthetically active leaves was attributed to an over-acidification of the cytoplasm. However, in the longer term, plasticity in the use of the different phases of gas exchange and different storage carbohydrate pools, i.e. a switch from starch to sucrose as the major carbohydrate source, ensured a positive carbon balance for this CAM species under extremely low levels of irradiance. As such, co-ordinated plasticity in the use of C(3) and C(4) carboxylases and different carbohydrate pools together with an increase in the abundance of light-harvesting complexes, appear to underpin the adaptive radiation of the energetically costly CAM pathway within light-limiting environments such as wet cloud forests and shaded understoreys of tropical forests. PMID:20861137

  17. Examination of metabolic responses to phosphorus limitation via proteomic analyses in the marine diatom Phaeodactylum tricornutum.

    PubMed

    Feng, Tian-Ya; Yang, Zhi-Kai; Zheng, Jian-Wei; Xie, Ying; Li, Da-Wei; Murugan, Shanmugaraj Bala; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2015-01-01

    Phosphorus (P) is an essential macronutrient for the survival of marine phytoplankton. In the present study, phytoplankton response to phosphorus limitation was studied by proteomic profiling in diatom Phaeodactylum tricornutum in both cellular and molecular levels. A total of 42 non-redundant proteins were identified, among which 8 proteins were found to be upregulated and 34 proteins were downregulated. The results also showed that the proteins associated with inorganic phosphate uptake were downregulated, whereas the proteins involved in organic phosphorus uptake such as alkaline phosphatase were upregulated. The proteins involved in metabolic responses such as protein degradation, lipid accumulation and photorespiration were upregulated whereas energy metabolism, photosynthesis, amino acid and nucleic acid metabolism tend to be downregulated. Overall our results showed the changes in protein levels of P. tricornutum during phosphorus stress. This study preludes for understanding the role of phosphorous in marine biogeochemical cycles and phytoplankton response to phosphorous scarcity in ocean. It also provides insight into the succession of phytoplankton community, providing scientific basis for elucidating the mechanism of algal blooms. PMID:26020491

  18. Examination of metabolic responses to phosphorus limitation via proteomic analyses in the marine diatom Phaeodactylum tricornutum

    PubMed Central

    Feng, Tian-Ya; Yang, Zhi-Kai; Zheng, Jian-Wei; Xie, Ying; Li, Da-Wei; Murugan, Shanmugaraj Bala; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2015-01-01

    Phosphorus (P) is an essential macronutrient for the survival of marine phytoplankton. In the present study, phytoplankton response to phosphorus limitation was studied by proteomic profiling in diatom Phaeodactylum tricornutum in both cellular and molecular levels. A total of 42 non-redundant proteins were identified, among which 8 proteins were found to be upregulated and 34 proteins were downregulated. The results also showed that the proteins associated with inorganic phosphate uptake were downregulated, whereas the proteins involved in organic phosphorus uptake such as alkaline phosphatase were upregulated. The proteins involved in metabolic responses such as protein degradation, lipid accumulation and photorespiration were upregulated whereas energy metabolism, photosynthesis, amino acid and nucleic acid metabolism tend to be downregulated. Overall our results showed the changes in protein levels of P. tricornutum during phosphorus stress. This study preludes for understanding the role of phosphorous in marine biogeochemical cycles and phytoplankton response to phosphorous scarcity in ocean. It also provides insight into the succession of phytoplankton community, providing scientific basis for elucidating the mechanism of algal blooms. PMID:26020491

  19. In vivo NMR study of yeast fermentative metabolism in the presence of ferric irons.

    PubMed

    Ricci, Maso; Martini, Silvia; Bonechi, Claudia; Braconi, Daniela; Santucci, Annalisa; Rossi, Claudio

    2011-03-01

    Mathematical modelling analysis of experimental data, obtained with in vivo NMR spectroscopy and 13C-labelled substrates, allowed us to describe how the fermentative metabolism in Saccharomyces cerevisiae, taken as eukaryotic cell model, is influenced by stress factors. Experiments on cellular cultures subject to increasing concentrations of ferric ions were conducted in order to study the effect of oxidative stress on the dynamics of the fermentative process. The developed mathematical model was able to simulate the cellular activity, the metabolic yield and the main metabolic fluxes occurring during fermentation and to describe how these are modulated by the presence of ferric ions. PMID:21451251

  20. Molecular pharmacology of the interaction of anthracyclines with iron.

    PubMed

    Xu, X; Persson, H L; Richardson, D R

    2005-08-01

    Although anthracyclines such as doxorubicin are widely used antitumor agents, a major limitation for their use is the development of cardiomyopathy at high cumulative doses. This severe adverse side effect may be due to interactions with cellular iron metabolism, because iron loading promotes anthracycline-induced cell damage. On the other hand, anthracycline-induced cardiotoxicity is significantly alleviated by iron chelators (e.g., desferrioxamine and dexrazoxane). The molecular mechanisms by which anthracyclines interfere with cellular iron trafficking are complex and still unclear. Doxorubicin can directly bind iron and can perturb iron metabolism by interacting with multiple molecular targets, including the iron regulatory proteins (IRP) 1 and 2. The RNA-binding activity of these molecules regulates synthesis of the transferrin receptor 1 and ferritin, which are crucial proteins involved in iron uptake and storage, respectively. At present, it is not clear whether doxorubicin affects IRP1-RNA-binding activity by intracellular formation of doxorubicinol and/or by generation of the doxorubicin-iron(III) complex. Furthermore, doxorubicin prevents the mobilization of iron from ferritin by a mechanism that may involve lysosomal degradation of this protein. Prevention of iron mobilization from ferritin would probably disturb vital cellular functions as a result of inhibition of essential iron-dependent proteins, such as ribonucleotide reductase. This review discusses the molecular interactions of anthracyclines with iron metabolism and the development of cardioprotective strategies such as iron chelators. PMID:15883202

  1. Arsenic Metabolism and Toxicity Influenced by Ferric Iron in Simulated Gastrointestinal Tract and the Roles of Gut Microbiota.

    PubMed

    Yu, Haiyan; Wu, Bing; Zhang, Xu-Xiang; Liu, Su; Yu, Jing; Cheng, Shupei; Ren, Hong-Qiang; Ye, Lin

    2016-07-01

    Iron (Fe) is a common trace element in drinking water. However, little is known about how environmental concentrations of Fe affect the metabolism and toxicity of arsenic (As) in drinking water. In this study, influence of Fe at drinking water-related concentrations (0.1, 0.3, and 3 mg Fe (total)/L) on As metabolism and toxicity, and the roles of gut microbiota during this process were investigated by using in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Results showed that Fe had ability to decrease bioaccessible As by coflocculation in small intestine. 0.1 and 0.3 mg/L Fe significantly increased As methylation in simulated transverse and descending colon. Gut microbiota played an important role in alteration of As species, and Fe could affect As metabolism by changing the gut microbiota. Bacteroides, Clostridium, Alistipes, and Bilophila had As resistance and potential ability to methylate As. Cytotoxicity assays of effluents from simulated colons showed that the low levels of Fe decreased As toxicity on human hepatoma cell line HepG2, which might be due to the increase of methylated As. When assessing the health risk of As in drinking water, the residual Fe should be considered. PMID:27280682

  2. The lysine biosynthetic enzyme Lys4 influences iron metabolism, mitochondrial function and virulence in Cryptococcus neoformans.

    PubMed

    Do, Eunsoo; Park, Minji; Hu, Guanggan; Caza, Mélissa; Kronstad, James W; Jung, Won Hee

    2016-09-01

    The lysine biosynthesis pathway via α-aminoadipate in fungi is considered an attractive target for antifungal drugs due to its absence in mammalian hosts. The iron-sulfur cluster-containing enzyme homoaconitase converts homocitrate to homoisocitrate in the lysine biosynthetic pathway, and is encoded by LYS4 in the model yeast Saccharomyces cerevisiae. In this study, we identified the ortholog of LYS4 in the human fungal pathogen, Cryptococcus neoformans, and found that LYS4 expression is regulated by iron levels and by the iron-related transcription factors Hap3 and HapX. Deletion of the LYS4 gene resulted in lysine auxotrophy suggesting that Lys4 is essential for lysine biosynthesis. Our study also revealed that lysine uptake was mediated by two amino acid permeases, Aap2 and Aap3, and influenced by nitrogen catabolite repression (NCR). Furthermore, the lys4 mutant showed increased sensitivity to oxidative stress, agents that challenge cell wall/membrane integrity, and azole antifungal drugs. We showed that these phenotypes were due in part to impaired mitochondrial function as a result of LYS4 deletion, which we propose disrupts iron homeostasis in the organelle. The combination of defects are consistent with our observation that the lys4 mutant was attenuated virulence in a mouse inhalation model of cryptococcosis. PMID:27353379

  3. Glutathione and iron at the crossroad of redox metabolism in rats infected by Trypanosoma evansi.

    PubMed

    Anschau, Valesca; Dafré, Alcir Luiz; Perin, Ana Paula; Iagher, Fabíola; Tizatto, Mayara Vieira; Miletti, Luiz Claudio

    2013-06-01

    The aim of this study was to evaluate the changes in hematological and biochemical parameters of blood during acute Trypanosoma evansi infection in Wistar rats. The end points studied were hematologic parameters, red blood cell fragility, iron content, and glutathione and lipid peroxidation levels. Forty-eight animals were infected with trypomastigotes and distributed into five groups according to the level of parasitemia. Twelve non-inoculated animals were used as control. Parasitemia increased progressively, reaching highest scores at 15 days post-inoculation. At this point, several deleterious effects were observed such as an increase in iron content, in osmotic fragility, and in lipid peroxidation index, while glutathione decreased drastically. These changes were highly correlated to parasitemia (p < 0.0001) and among each other (p ≤ 0.001). Hematological indices (Hb, packed cell volume (PCV), red blood cells (RBC), and mean corpuscular hemoglobin concentration) were also correlated to parasitemia (p ≤ 0.0003) but failed to correlate to the other variables. Along with increase in iron, RBC fragility produced a decrease in RBC, PCV, and Hb, but not in mean corpuscular volume. Decrease in glutathione was negatively correlated to the end products of lipid peroxidation, clearly indicating the establishment of a pro-oxidant condition. The results show that the infection causes hematological impairments, increases iron and osmotic fragility, along with marked oxidative stress in red blood cells of rats inoculated with T. evansi. PMID:23529337

  4. Hepcidin and Iron Metabolism in Pregnancy: Correlation with Smoking and Birth Weight and Length.

    PubMed

    Chełchowska, Magdalena; Ambroszkiewicz, Jadwiga; Gajewska, Joanna; Jabłońska-Głąb, Ewa; Maciejewski, Tomasz M; Ołtarzewski, Mariusz

    2016-09-01

    To estimate the effect of tobacco smoking on iron homeostasis and the possible association between hepcidin and the neonatal birth weight and length, concentrations of serum hepcidin and selected iron markers were measured in 81 healthy pregnant women (41 smokers and 40 nonsmokers). The smoking mothers had significantly lower concentrations of serum hepcidin (p < 0.001), iron (p < 0.001), and hemoglobin (p < 0.05), but higher erythropoietin (p < 0.05) levels compared with non-smoking pregnant women. Logistic regression analysis showed the highest negative impact of the number of cigarettes smoked per day (β = -0.46; p < 0.01) and positive impact of ferritin level (β = 0.47; p < 0.001) on serum hepcidin concentration. The birth weight and the body length of smoking mothers' infants were significantly lower than in tobacco abstinent group (p < 0.001). In multiple regression analysis, birth body weight (β = 0.56; p < 0.001) and length (β = 0.50; p < 0.001) were significantly related to maternal hepcidin values. Tobacco smoking affected hepcidin level in serum of pregnant women in a dose-dependent manner. Low concentrations of iron and hemoglobin in maternal serum coexisting with high level of erythropoietin suggest that smoking could lead to subclinical iron deficiency and chronic hypoxia not only in mothers but also in fetus. Low serum hepcidin concentration in smoking pregnant women might be associated with lower fetal birth weight and length. PMID:26785641

  5. Iron limitation enhances acyl homoserine lactone (AHL) production and biofilm formation in clinical isolates of Acinetobacter baumannii

    PubMed Central

    Modarresi, Farzan; Azizi, Omid; Shakibaie, Mohammad Reza; Motamedifar, Mohammad; Mosadegh, Ellahe; Mansouri, Shahla

    2015-01-01

    Abstract Acinetobacter baumannii is an important source of infections in intensive care units (ICUs) of our hospitals in Kerman, Iran and the most frequently isolated strains produce biofilm. There is a little information about role of iron (Fe) levels on acyl homoserine lactone (AHL) production and biofilm formation in this microorganism. In the present study, we investigated the influence of iron-III limitation on AHL, siderophore, catechol and virulence factors in the biofilm forming clinical strains of A. baumannii. A total of 65 non-duplicated multidrug resistance (MDR) strains of A. baumannii were isolated from patients in ICUs of 2 hospitals in Kerman, Iran. Antibiotic susceptibility, siderophore and other iron chelators, hemolysis, cell twitching motility, capsule, gelatinase and DNase were studied. Presence of quorum sensing, LuxI and LuxR genes was detected by multiplex-PCR. AHL activity quantified by colorimetric method and the functional groups were determined by Fourier Transform Infra-Red Spectroscopy (FT-IR). Biofilm formation was detected by microtiter plate technique. All of the isolates were resistant to third generation of cephalosporins, ciprofloxacin, levofloxacin, tetracycline, whereas, 78% and 81% were resistant to amikacin and carbapenems, respectively. The siderophore activity was highest at 20 μM Fe3+ (70%); however, it decreased to 45% as concentration of Fe3+ increased to 80 μM. Furthermore, screening of the isolates for LuxI and LuxR genes showed that presence of both genes required in the isolates with high AHL activity. FT-IR analysis indicated C=O bond of the lactone ring and primary amides. Significantly, a higher amount of AHL (70%) was detected in the presence of low concentration of iron-III (20 μM); as iron concentration increased to 80 μM, the AHL activity was reduced to 40% (P ≤ 0.05). All the isolates exhibited twitching motility and had a capsule. No any gelatinase or DNase activity was detected. Quantification of

  6. Oral administration of iron-saturated bovine lactoferrin–loaded ceramic nanocapsules for breast cancer therapy and influence on iron and calcium metabolism

    PubMed Central

    Mahidhara, Ganesh; Kanwar, Rupinder K; Roy, Kislay; Kanwar, Jagat R

    2015-01-01

    We determined the anticancer efficacy and internalization mechanism of our polymeric–ceramic nanoparticle system (calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate nanocapsules/nanocarriers [ACSC NCs]) loaded with iron-saturated bovine lactoferrin (Fe-bLf) in a breast cancer xenograft model. ACSC-Fe-bLf NCs with an overall size of 322±27.2 nm were synthesized. In vitro internalization and anticancer efficacy were evaluated in the MDA-MB-231 cells using multicellular tumor spheroids, CyQUANT and MTT assays. These NCs were orally delivered in a breast cancer xenograft mice model, and their internalization, cytotoxicity, biodistribution, and anticancer efficacy were evaluated. Chitosan-coated calcium phosphate Fe-bLf NCs effectively (59%, P≤0.005) internalized in a 1-hour period using clathrin-mediated endocytosis (P≤0.05) and energy-mediated pathways (P≤0.05) for internalization; 3.3 mg/mL of ACSC-Fe-bLf NCs completely disintegrated (~130-fold reduction, P≤0.0005) the tumor spheroids in 72 hours and 96 hours. The IC50 values determined for ACSC-Fe-bLf NCs were 1.69 mg/mL at 10 hours and 1.62 mg/mL after 20 hours. We found that Fe-bLf-NCs effectively (P≤0.05) decreased the tumor size (4.8-fold) compared to the void NCs diet and prevented tumor recurrence when compared to intraperitoneal injection of Taxol and Doxorubicin. Receptor gene expression and micro-RNA analysis confirmed upregulation of low-density lipoprotein receptor and transferrin receptor (liver, intestine, and brain). Several micro-RNAs responsible for iron metabolism upregulated with NCs were identified. Taken together, orally delivered Fe-bLf NCs offer enhanced antitumor activity in breast cancer by internalizing via low-density lipoprotein receptor and transferrin receptor and regulating the micro-RNA expression. These NCs also restored the body iron and calcium levels and increased the hematologic counts. PMID:26124661

  7. Metabolic flexibility of the Fe(II)-oxidizing phototropic strain Rhodopseudomonas palustris TIE1 and its potential role in microbial iron cycling

    NASA Astrophysics Data System (ADS)

    Schmidt, C.; Oswald, K.; Melton, E. D.; Kappler, A.

    2012-04-01

    The biogeochemical conversion of iron(II) and iron(III) is widespread in many aquatic and terrestrial environments. In the anoxic regime of soils and sediments the conversion and alternation of the iron redox state is predominantly run by microorganisms that are thought to gain life-sustaining energy by the oxidation and/or reduction of ferrous/ferric components. The spatial arrangement of microbial iron(II) oxidation and iron(III) reduction is largely controlled by the availability of the required electron acceptor and electron donor, as well as the essential source of energy (i.e. light or chemical energy). The physico-chemical patterns of many microbial environments undergo dynamic variations (i.e. diurnal and seasonal changes) as a function of natural external forces (i.e. seasonality, storm events, algae blooms) which strongly affects the local budget of organic carbon and nutrients, as well as the day light penetration. Such fluctuations force microorganisms either to follow the flow of substrate or to switch their metabolism to alternative electron acceptors and/or donors. Different photoferrotrophic bacteria have been shown to be able to grow either on organic (heterotrophic) or inorganic (autotrophic) substrates while exploiting light as their energy source. Within the frame of this study the preference for organic substrates (lactate and acetate) and/or ferrous iron (in simultaneous presence) for photo(ferro)trophic growth of Rhodopseudomonas palustris TIE1 has been investigated in detail. Rates of iron oxidation, acetate/lactate consumption and growth have been followed over time as a function of different lactate to acetate to iron(II) ratios. Additional experiments have been designed to evaluate the potential of Rhodopseudomonas palustris TIE1 to contribute to the redox cycling of iron. TIE1 has been grown in a batch set-up in which the iron(III)-reducing strain Shewanella oneidensis MR1 has been incubated at different ferrihydrite concentrations in

  8. Metabolic responses to iron deficiency in roots of Carrizo citrange [Citrus sinensis (L.) Osbeck. x Poncirus trifoliata (L.) Raf].

    PubMed

    Martínez-Cuenca, Mary-Rus; Iglesias, Domingo J; Talón, Manuel; Abadía, Javier; López-Millán, Ana-Flor; Primo-Millo, Eduardo; Legaz, Francisco

    2013-03-01

    The effects of iron (Fe) deficiency on the low-molecular-weight organic acid (LMWOA) metabolism have been investigated in Carrizo citrange (CC) [Citrus sinensis (L.) Osb. × Poncirus trifoliata (L.) Raf.] roots. Major LMWOAs found in roots, xylem sap and root exudates were citrate and malate and their concentrations increased with Fe deficiency. The activities of several enzymes involved in the LMWOA metabolism were also assessed in roots. In the cytosolic fraction, the activities of malate dehydrogenase (cMDH) and phosphoenolpyruvate carboxylase (PEPC) enzymes were 132 and 100% higher in Fe-deficient conditions, whereas the activity of pyruvate kinase was 31% lower and the activity of malic enzyme (ME) did not change. In the mitochondrial fraction, the activities of fumarase, MDH and citrate synthase enzymes were 158, 117 and 53% higher, respectively, in Fe-deficient extracts when compared with Fe-sufficient controls, whereas no significant differences between treatments were found for aconitase (ACO) activity. The expression of their corresponding genes in roots of Fe-deficient plants was higher than that measured in Fe-sufficient controls, except for ACO and ME. Also, dicarboxylate-tricarboxylate carrier (DTC) expression was significantly increased in Fe-deficient roots. In conclusion, Fe deficiency in CC seedlings causes a reprogramming of the carbon metabolism that involves an increase of anaplerotic fixation of carbon via PEPC and MDH activities in the cytosol and a shift of the Krebs cycle in the mitochondria towards a non-cyclic mode, as previously described in herbaceous species. In this scheme, DTC could play an important role shuttling both malate and reducing equivalents between the cytosol and the mitochondria. As a result of this metabolic switch malate and citrate concentrations in roots, xylem sap and root exudates increase. PMID:23462311

  9. The effects of polysaccharides from the root of Angelica sinensis on tumor growth and iron metabolism in H22-bearing mice.

    PubMed

    Cheng, Yao; Zhou, Jiali; Li, Qiang; Liu, Ying; Wang, Kaiping; Zhang, Yu

    2016-02-01

    The crude polysaccharide was obtained from the root of Angelica sinensis (AS) to investigate its effect on tumor growth and iron metabolism in H22-bearing mice. In our study, we showed that Angelica sinensis polysaccharide (ASP) was mainly composed of arabinose, glucose and galactose in a molar ratio of 1:1:1.75, with a molecular weight of 80,900 Da and a sugar content of 88.0%. Animal experimental results revealed that three doses of ASP all had anti-tumor effects with inhibition ratios of 27.11%, 31.65% and 37.05%. With respect to iron metabolism, the mean levels of serum hepcidin, interleukin-6 (IL-6), ferritin, transferrin (Tf), transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2) in H22-bearing mice were promoted, and serum iron concentration decreased significantly. After treatment with ASP, these iron-related indicators recovered in different degrees. The findings suggested that the anti-tumor activity of ASP may be affected by its regulation on iron metabolism in H22-bearing mice. PMID:26757699

  10. Diurnal variation in the coupling of photosynthetic electron transport and carbon fixation in iron-limited phytoplankton in the NE subarctic Pacific

    NASA Astrophysics Data System (ADS)

    Schuback, N.; Flecken, M.; Maldonado, M. T.; Tortell, P. D.

    2015-10-01

    Active chlorophyll a fluorescence approaches, including fast repetition rate fluorometry (FRRF), have the potential to provide estimates of phytoplankton primary productivity at unprecedented spatial and temporal resolution. FRRF-derived productivity rates are based on estimates of charge separation at PSII (ETRRCII), which must be converted into ecologically relevant units of carbon fixation. Understanding sources of variability in the coupling of ETRRCII and carbon fixation provides physiological insight into phytoplankton photosynthesis, and is critical for the application of FRRF as a primary productivity measurement tool. In the present study, we simultaneously measured phytoplankton carbon fixation and ETRRCII in the iron-limited NE subarctic Pacific, over the course of a diurnal cycle. We show that rates of ETRRCII are closely tied to the diurnal cycle in light availability, whereas rates of carbon fixation appear to be influenced by endogenous changes in metabolic energy allocation under iron-limited conditions. Unsynchronized diurnal oscillations of the two rates led to 3.5 fold changes in the conversion factor coupling ETRRCII and carbon fixation (Φe:C / nPSII). Consequently, diurnal variability in phytoplankton carbon fixation cannot be adequately captured with FRRF approaches if a constant conversion factor is applied. Utilizing several auxiliary photophysiological measurements, we observed that a high conversion factor is associated with conditions of excess light, and correlates with the expression of non-photochemical quenching (NPQ) in the pigment antenna, as derived from FRRF measurements. The observed correlation between NPQ and the conversion factor Φe:C / nPSII has the potential to improve estimates of phytoplankton carbon fixation rates from FRRF measurements alone.

  11. Diurnal variation in the coupling of photosynthetic electron transport and carbon fixation in iron-limited phytoplankton in the NE subarctic Pacific

    NASA Astrophysics Data System (ADS)

    Schuback, Nina; Flecken, Mirkko; Maldonado, Maria T.; Tortell, Philippe D.

    2016-02-01

    Active chlorophyll a fluorescence approaches, including fast repetition rate fluorometry (FRRF), have the potential to provide estimates of phytoplankton primary productivity at an unprecedented spatial and temporal resolution. FRRF-derived productivity rates are based on estimates of charge separation in reaction center II (ETRRCII), which must be converted into ecologically relevant units of carbon fixation. Understanding sources of variability in the coupling of ETRRCII and carbon fixation provides physiological insight into phytoplankton photosynthesis and is critical for the application of FRRF as a primary productivity measurement tool. In the present study, we simultaneously measured phytoplankton carbon fixation and ETRRCII in the iron-limited NE subarctic Pacific over the course of a diurnal cycle. We show that rates of ETRRCII are closely tied to the diurnal cycle in light availability, whereas rates of carbon fixation appear to be influenced by endogenous changes in metabolic energy allocation under iron-limited conditions. Unsynchronized diurnal oscillations of the two rates led to 3.5-fold changes in the conversion factor between ETRRCII and carbon fixation (Kc / nPSII). Consequently, diurnal variability in phytoplankton carbon fixation cannot be adequately captured with FRRF approaches if a constant conversion factor is applied. Utilizing several auxiliary photophysiological measurements, we observed that a high conversion factor is associated with conditions of excess light and correlates with the increased expression of non-photochemical quenching (NPQ) in the pigment antenna, as derived from FRRF measurements. The observed correlation between NPQ and Kc / nPSII requires further validation but has the potential to improve estimates of phytoplankton carbon fixation rates from FRRF measurements alone.

  12. Partitioning the metabolic scope: the importance of anaerobic metabolism and implications for the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis.

    PubMed

    Ejbye-Ernst, Rasmus; Michaelsen, Thomas Y; Tirsgaard, Bjørn; Wilson, Jonathan M; Jensen, Lasse F; Steffensen, John F; Pertoldi, Cino; Aarestrup, Kim; Svendsen, Jon C

    2016-01-01

    Ongoing climate change is predicted to affect the distribution and abundance of aquatic ectotherms owing to increasing constraints on organismal physiology, in particular involving the metabolic scope (MS) available for performance and fitness. The oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis prescribes MS as an overarching benchmark for fitness-related performance and assumes that any anaerobic contribution within the MS is insignificant. The MS is typically derived from respirometry by subtracting standard metabolic rate from the maximal metabolic rate; however, the methodology rarely accounts for anaerobic metabolism within the MS. Using gilthead sea bream (Sparus aurata) and Trinidadian guppy (Poecilia reticulata), this study tested for trade-offs (i) between aerobic and anaerobic components of locomotor performance; and (ii) between the corresponding components of the MS. Data collection involved measuring oxygen consumption rate at increasing swimming speeds, using the gait transition from steady to unsteady (burst-assisted) swimming to detect the onset of anaerobic metabolism. Results provided evidence of the locomotor performance trade-off, but only in S. aurata. In contrast, both species revealed significant negative correlations between aerobic and anaerobic components of the MS, indicating a trade-off where both components of the MS cannot be optimized simultaneously. Importantly, the fraction of the MS influenced by anaerobic metabolism was on average 24.3 and 26.1% in S. aurata and P. reticulata, respectively. These data highlight the importance of taking anaerobic metabolism into account when assessing effects of environmental variation on the MS, because the fraction where anaerobic metabolism occurs is a poor indicator of sustainable aerobic performance. Our results suggest that without accounting for anaerobic metabolism within the MS, studies involving the OCLTT hypothesis could overestimate the metabolic scope available for

  13. Partitioning the metabolic scope: the importance of anaerobic metabolism and implications for the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis

    PubMed Central

    Ejbye-Ernst, Rasmus; Michaelsen, Thomas Y.; Tirsgaard, Bjørn; Wilson, Jonathan M.; Jensen, Lasse F.; Steffensen, John F.; Pertoldi, Cino; Aarestrup, Kim; Svendsen, Jon C.

    2016-01-01

    Ongoing climate change is predicted to affect the distribution and abundance of aquatic ectotherms owing to increasing constraints on organismal physiology, in particular involving the metabolic scope (MS) available for performance and fitness. The oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis prescribes MS as an overarching benchmark for fitness-related performance and assumes that any anaerobic contribution within the MS is insignificant. The MS is typically derived from respirometry by subtracting standard metabolic rate from the maximal metabolic rate; however, the methodology rarely accounts for anaerobic metabolism within the MS. Using gilthead sea bream (Sparus aurata) and Trinidadian guppy (Poecilia reticulata), this study tested for trade-offs (i) between aerobic and anaerobic components of locomotor performance; and (ii) between the corresponding components of the MS. Data collection involved measuring oxygen consumption rate at increasing swimming speeds, using the gait transition from steady to unsteady (burst-assisted) swimming to detect the onset of anaerobic metabolism. Results provided evidence of the locomotor performance trade-off, but only in S. aurata. In contrast, both species revealed significant negative correlations between aerobic and anaerobic components of the MS, indicating a trade-off where both components of the MS cannot be optimized simultaneously. Importantly, the fraction of the MS influenced by anaerobic metabolism was on average 24.3 and 26.1% in S. aurata and P. reticulata, respectively. These data highlight the importance of taking anaerobic metabolism into account when assessing effects of environmental variation on the MS, because the fraction where anaerobic metabolism occurs is a poor indicator of sustainable aerobic performance. Our results suggest that without accounting for anaerobic metabolism within the MS, studies involving the OCLTT hypothesis could overestimate the metabolic scope available for

  14. Microbial communities from different subsystems in biological heap leaching system play different roles in iron and sulfur metabolisms.

    PubMed

    Xiao, Yunhua; Liu, Xueduan; Ma, Liyuan; Liang, Yili; Niu, Jiaojiao; Gu, Yabing; Zhang, Xian; Hao, Xiaodong; Dong, Weiling; She, Siyuan; Yin, Huaqun

    2016-08-01

    The microbial communities are important for minerals decomposition in biological heap leaching system. However, the differentiation and relationship of composition and function of microbial communities between leaching heap (LH) and leaching solution (LS) are still unclear. In this study, 16S rRNA gene sequencing was used to assess the microbial communities from the two subsystems in ZiJinShan copper mine (Fujian province, China). Results of PCoA and dissimilarity test showed that microbial communities in LH samples were significantly different from those in LS samples. The dominant genera of LH was Acidithiobacillus (57.2 ∼ 87.9 %), while Leptospirillum (48.6 ∼ 73.7 %) was predominant in LS. Environmental parameters (especially pH) were the major factors to influence the composition and structure of microbial community by analysis of Mantel tests. Results of functional test showed that microbial communities in LH utilized sodium thiosulfate more quickly and utilized ferrous sulfate more slowly than those in LS, which further indicated that the most sulfur-oxidizing processes of bioleaching took place in LH and the most iron-oxidizing processes were in LS. Further study found that microbial communities in LH had stronger pyrite leaching ability, and iron extraction efficiency was significantly positively correlated with Acidithiobacillus (dominated in LH), which suggested that higher abundance ratio of sulfur-oxidizing microbes might in favor of minerals decomposition. Finally, a conceptual model was designed through the above results to better exhibit the sulfur and iron metabolism in bioleaching systems. PMID:27094188

  15. Development of a Quantitative SRM-Based Proteomics Method to Study Iron Metabolism of Synechocystis sp. PCC 6803.

    PubMed

    Vuorijoki, Linda; Isojärvi, Janne; Kallio, Pauli; Kouvonen, Petri; Aro, Eva-Mari; Corthals, Garry L; Jones, Patrik R; Muth-Pawlak, Dorota

    2016-01-01

    The cyanobacterium Synechocystis sp. PCC 6803 (S. 6803) is a well-established model species in oxygenic photosynthesis research and a potential host for biotechnological applications. Despite recent advances in genome sequencing and microarray techniques applied in systems biology, quantitative proteomics approaches with corresponding accuracy and depth are scarce for S. 6803. In this study, we developed a protocol to screen changes in the expression of 106 proteins representing central metabolic pathways in S. 6803 with a targeted mass spectrometry method, selected reaction monitoring (SRM). We evaluated the response to the exposure of both short- and long-term iron deprivation. The experimental setup enabled the relative quantification of 96 proteins, with 87 and 92 proteins showing adjusted p-values <0.01 under short- and long-term iron deficiency, respectively. The high sensitivity of the SRM method for S. 6803 was demonstrated by providing quantitative data for altogether 64 proteins that previously could not be detected with the classical data-dependent MS approach under similar conditions. This highlights the effectiveness of SRM for quantification and extends the analytical capability to low-abundance proteins in unfractionated samples of S. 6803. The SRM assays and other generated information are now publicly available via PASSEL and Panorama. PMID:26652789

  16. JAK2 exon 12 mutant mice display isolated erythrocytosis and changes in iron metabolism favoring increased erythropoiesis.

    PubMed

    Grisouard, Jean; Li, Sai; Kubovcakova, Lucia; Rao, Tata Nageswara; Meyer, Sara C; Lundberg, Pontus; Hao-Shen, Hui; Romanet, Vincent; Murakami, Masato; Radimerski, Thomas; Dirnhofer, Stephan; Skoda, Radek C

    2016-08-11

    Mutations in JAK2 exon 12 are frequently found in patients with polycythemia vera (PV) that do not carry a JAK2-V617F mutation. The majority of these patients display isolated erythrocytosis. We generated a mouse model that expresses JAK2-N542-E543del, the most frequent JAK2 exon 12 mutation found in PV patients. Mice expressing the human JAK2-N542-E543del (Ex12) showed a strong increase in red blood cell parameters but normal neutrophil and platelet counts, and reduced overall survival. Erythropoiesis was increased in the bone marrow and spleen, with normal megakaryopoiesis and absence of myelofibrosis in histopathology. Erythroid progenitors and precursors were increased in hematopoietic tissues, but the numbers of megakaryocytic precursors were unchanged. Phosphorylation Stat3 and Erk1/2 proteins were increased, and a trend toward increased phospho-Stat5 and phospho-Stat1 was noted. However, Stat1 knock out in Ex12 mice induced no changes in platelet or red cell parameters, indicating that Stat1 does not play a central role in mediating the effects of Ex12 signaling on megakaryopoiesis or erythropoiesis. Ex12 mice showed decreased expression of hepcidin and increased expression of transferrin receptor-1 and erythroferrone, suggesting that the strong erythroid phenotype in Ex12 mutant mice is favored by changes in iron metabolism that optimize iron availability to allow maximal production of red cells. PMID:27288519

  17. Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

    PubMed Central

    Samarakoon, Thilani N; Yapa, Asanka S; Abayaweera, Gayani; Basel, Matthew T; Maynez, Pamela; Ortega, Raquel; Toledo, Yubisela; Bossmann, Leonie; Robinson, Colette; Janik, Katharine E; Koper, Olga B; Li, Ping; Motamedi, Massoud; Higgins, Daniel A; Gadbury, Gary

    2016-01-01

    Summary Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis. PMID:27335730

  18. Iron deficiency.

    PubMed

    Scrimshaw, N S

    1991-10-01

    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world. PMID:1745900

  19. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    PubMed

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH < pK). Steady states were achieved with different extracellular levels of fumaric acid, obtained by adding different amounts of fumaric acid to the feed medium. The experiments were carried out with the wild-type S. cerevisiae CEN.PK 113-7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT-02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26683700

  20. Nitrogen metabolism of two contrasting poplar species during acclimation to limiting nitrogen availability

    PubMed Central

    Luo, Zhi-Bin

    2013-01-01

    To investigate N metabolism of two contrasting Populus species in acclimation to low N availability, saplings of slow-growing species (Populus popularis, Pp) and a fast-growing species (Populus alba × Populus glandulosa, Pg) were exposed to 10, 100, or 1000 μM NH4NO3. Despite greater root biomass and fine root surface area in Pp, lower net influxes of NH4 + and NO3 – at the root surface were detected in Pp compared to those in Pg, corresponding well to lower NH4 + and NO3 – content and total N concentration in Pp roots. Meanwhile, higher stable N isotope composition (δ15N) in roots and stronger responsiveness of transcriptional regulation of 18 genes involved in N metabolism were found in roots and leaves of Pp compared to those of Pg. These results indicate that the N metabolism of Pp is more sensitive to decreasing N availability than that of Pg. In both species, low N treatments decreased net influxes of NH4 + and NO3 –, root NH4 + and foliar NO3 – content, root NR activities, total N concentration in roots and leaves, and transcript levels of most ammonium (AMTs) and nitrate (NRTs) transporter genes in leaves and genes involved in N assimilation in roots and leaves. Low N availability increased fine root surface area, foliar starch concentration, δ15N in roots and leaves, and transcript abundance of several AMTs (e.g. AMT1;2) and NRTs (e.g. NRT1;2 and NRT2;4B) in roots of both species. These data indicate that poplar species slow down processes of N acquisition and assimilation in acclimation to limiting N supply. PMID:23963674

  1. Current limiting behavior in three-phase transformer-type SFCLs using an iron core according to variety of fault

    NASA Astrophysics Data System (ADS)

    Cho, Yong-Sun; Jung, Byung-Ik; Ha, Kyoung-Hun; Choi, Soo-Geun; Park, Hyoung-Min; Choi, Hyo-Sang

    To apply the superconducting fault current limiter (SFCL) to the power system, the reliability of the fault-current-limiting operation must be ensured in diverse fault conditions. The SFCL must also be linked to the operation of the high-speed recloser in the power system. In this study, a three-phase transformer-type SFCL, which has a neutral line to improve the simultaneous quench characteristics of superconducting elements, was manufactured to analyze the fault-current-limiting characteristic according to the single, double, and triple line-to-ground faults. The transformer-type SFCL, wherein three-phase windings are connected to one iron core, reduced the burden on the superconducting element as the superconducting element on the sound phase was also quenched in the case of the single line-to-ground fault. In the case of double or triple line-to-ground faults, the flux from the faulted phase winding was interlinked with other faulted or sound phase windings, and the fault-current-limiting rate decreased because the windings of three phases were inductively connected by one iron core.

  2. Changes in the proteomic and metabolic profiles of Beta vulgaris root tips in response to iron deficiency and resupply

    PubMed Central

    2010-01-01

    Background Plants grown under iron deficiency show different morphological, biochemical and physiological changes. These changes include, among others, the elicitation of different strategies to improve the acquisition of Fe from the rhizosphere, the adjustment of Fe homeostasis processes and a reorganization of carbohydrate metabolism. The application of modern techniques that allow the simultaneous and untargeted analysis of multiple proteins and metabolites can provide insight into multiple processes taking place in plants under Fe deficiency. The objective of this study was to characterize the changes induced in the root tip proteome and metabolome of sugar beet plants in response to Fe deficiency and resupply. Results Root tip extract proteome maps were obtained by 2-D isoelectric focusing polyacrylamide gel electrophoresis, and approximately 140 spots were detected. Iron deficiency resulted in changes in the relative amounts of 61 polypeptides, and 22 of them were identified by mass spectrometry (MS). Metabolites in root tip extracts were analyzed by gas chromatography-MS, and more than 300 metabolites were resolved. Out of 77 identified metabolites, 26 changed significantly with Fe deficiency. Iron deficiency induced increases in the relative amounts of proteins and metabolites associated to glycolysis, tri-carboxylic acid cycle and anaerobic respiration, confirming previous studies. Furthermore, a protein not present in Fe-sufficient roots, dimethyl-8-ribityllumazine (DMRL) synthase, was present in high amounts in root tips from Fe-deficient sugar beet plants and gene transcript levels were higher in Fe-deficient root tips. Also, a marked increase in the relative amounts of the raffinose family of oligosaccharides (RFOs) was observed in Fe-deficient plants, and a further increase in these compounds occurred upon short term Fe resupply. Conclusions The increases in DMRL synthase and in RFO sugars were the major changes induced by Fe deficiency and resupply

  3. Aggregatibacter actinomycetemcomitans QseBC is activated by catecholamines and iron and regulates genes encoding proteins associated with anaerobic respiration and metabolism

    PubMed Central

    Weigel, WA; Demuth, DR; Torres-Escobar, A; Juárez-Rodríguez, MD

    2015-01-01

    Aggregatibacter actinomycetemcomitans QseBC regulates its own expression and is essential for biofilm growth and virulence. However, the signal that activates the QseC sensor has not been identified and the qseBC regulon has not been defined. In this study, we show that QseC is activated by catecholamine hormones and iron but not by either component alone. Activation of QseC requires an EYRDD motif in the periplasmic domain of the sensor and site-specific mutations in EYRDD or the deletion of the periplasmic domain inhibits catecholamine/iron-dependent induction of the ygiW-qseBC operon. Catecholamine/iron-dependent induction of transcription also requires interaction of the QseB response regulator with its binding site in the ygiW-qseBC promoter. Whole genome microarrays were used to compare gene expression profiles of A. actinomycetemcomitans grown in a chemically defined medium with and without catecholamine and iron supplementation. Approximately 11.5% of the A. actinomycetemcomitans genome was differentially expressed by at least two-fold upon exposure to catecholamines and iron. The expression of ferritin was strongly induced, suggesting that intracellular iron storage capacity is increased upon QseBC activation. Consistent with this, genes encoding iron binding and transport proteins were down-regulated by QseBC. Strikingly, 57% of the QseBC up-regulated genes (56/99) encode proteins associated with anaerobic metabolism and respiration. Most of these up-regulated genes were recently reported to be induced during in vivo growth of A. actinomycetemcomitans. These results suggest that detection of catecholamines and iron by QseBC may alter the cellular metabolism of A. actinomycetemcomitans for increased fitness and growth in an anaerobic host environment. PMID:25923132

  4. Role of secondary metabolites in the interaction between Pseudomonas fluorescens and soil microorganisms under iron-limited conditions.

    PubMed

    Deveau, Aurélie; Gross, Harald; Palin, Béatrice; Mehnaz, Samina; Schnepf, Max; Leblond, Pierre; Dorrestein, Pieter C; Aigle, Bertrand

    2016-08-01

    Microorganisms can be versatile in their interactions with each other, being variously beneficial, neutral or antagonistic in their effect. Although this versatility has been observed among many microorganisms and in many environments, little is known regarding the mechanisms leading to these changes in behavior. In the present work, we analyzed the mechanism by which the soil bacterium Pseudomonas fluorescens BBc6R8 shifts from stimulating the growth of the ectomycorrhizal fungus Laccaria bicolor S238N to killing the fungus. We show that among the three secondary metabolites produced by the bacterial strain-the siderophores enantio-pyochelin and pyoverdine, and the biosurfactant viscosin-the siderophores are mainly responsible for the antagonistic activity of the bacterium under iron-limited conditions. While the bacterial strain continues to produce beneficial factors, their effects are overridden by the action of their siderophores. This antagonistic activity of the strain P. fluorescens BBC6R8 in iron-depleted environments is not restricted to its influence on L. bicolor, since it was also seen to inhibit the growth of the actinomycete Streptomyces ambofaciens ATCC23877. We show that the strain P. fluorescens BBc6R8 uses different strategies to acquire iron, depending on certain biotic and abiotic factors. PMID:27199346

  5. Iron-Induced Changes in the Proteome of Trichomonas vaginalis Hydrogenosomes

    PubMed Central

    Beltrán, Neritza Campo; Horváthová, Lenka; Jedelský, Petr L.; Šedinová, Miroslava; Rada, Petr; Marcinčiková, Michaela; Hrdý, Ivan; Tachezy, Jan

    2013-01-01

    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. PMID:23741475

  6. We still say iron deficiency limits phytoplankton growth in the Subarctic Pacific

    NASA Astrophysics Data System (ADS)

    Martin, John H.; Fitzwater, Steve E.; Gordon, R. Michael

    1991-11-01

    The failure of Banse (1990) to use a reasonable initial particulate organic nitrogen (PON) value resulted in erroneously high, and physiologically impossible, estimates of phytoplankton growth rates. To correct this situation, we used an initial PON value of 1 μmol PON L-1 for both experimentals and controls; rates similar to those expected under prevailing light and temperature conditions were obtained. This reinterpretation of our data again demonstrates the dramatic effects that are observed when small quantities of iron are made available to the phytoplankton inhabiting offshore subarctic Pacific waters.

  7. Increase in cellular pool of low-molecular-weight iron during ethanol metabolism in rat hepatocyte cultures. Relationship with lipid peroxidation.

    PubMed

    Sergent, O; Morel, I; Cogrel, P; Chevanne, M; Pasdeloup, N; Brissot, P; Lescoat, G; Cillard, P; Cillard, J

    1995-01-01

    Ethanol-induced lipid peroxidation was studied in primary rat hepatocyte cultures supplemented with ethanol at the concentration of 50 mM. Lipid peroxidation was assessed by two indices: (1) conjugated dienes by second-derivative UV spectroscopy in lipid extract of hepatocytes (intracellular content), and (2) free malondialdehyde (MDA) by HPLC-UV detection and quantitation for the incubation medium (extracellular content). In cultures supplemented with ethanol, free MDA increased significantly in culture media, whereas no elevation of conjugated diene level was observed in the corresponding hepatocytes. The cellular pool of low-mol-wt (LMW) iron was also evaluated in the hepatocytes using an electron spin resonance procedure. An early increase of intracellular LMW iron (< or = 1 hr) was observed in ethanol-supplemented cultures; it was inhibited by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, whereas alpha-tocopherol, which prevented lipid peroxidation, did not inhibit the increase of LMW iron. Therefore, the LMW iron elevation was the result of ethanol metabolism and was not secondarily induced by lipid hydroperoxides. Thus, ethanol caused lipid peroxidation in rat hepatocytes as shown by the increase of free MDA, although no conjugated diene elevation was detected. During ethanol metabolism, an increase in cellular LMW iron was observed that could enhance conjugated diene degradation. PMID:7779546

  8. Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle

    PubMed Central

    Barrientos, Tomasa; Laothamatas, Indira; Koves, Timothy R.; Soderblom, Erik J.; Bryan, Miles; Moseley, M. Arthur; Muoio, Deborah M.; Andrews, Nancy C.

    2015-01-01

    Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that iron assimilation via Tfr1 was critical for skeletal muscle metabolism, and that iron deficiency in muscle led to dramatic changes, not only in muscle, but also in adipose tissue and liver. Inactivation of Tfr1 incapacitated normal energy production in muscle, leading to growth arrest and a muted attempt to switch to fatty acid β oxidation, using up fat stores. Starvation signals stimulated gluconeogenesis in the liver, but amino acid substrates became limiting and hypoglycemia ensued. Surprisingly, the liver was also iron deficient, and production of the iron regulatory hormone hepcidin was depressed. Our observations reveal a complex interaction between iron homeostasis and metabolism that has implications for metabolic and iron disorders. PMID:26870796

  9. Metabolic and diffusional limitations of photosynthesis in fluctuating irradiance in Arabidopsis thaliana

    PubMed Central

    Kaiser, Elias; Morales, Alejandro; Harbinson, Jeremy; Heuvelink, Ep; Prinzenberg, Aina E.; Marcelis, Leo F. M.

    2016-01-01

    A better understanding of the metabolic and diffusional limitations of photosynthesis in fluctuating irradiance can help identify targets for improving crop yields. We used different genotypes of Arabidopsis thaliana to characterise the importance of Rubisco activase (Rca), stomatal conductance (gs), non-photochemical quenching of chlorophyll fluorescence (NPQ) and sucrose phosphate synthase (SPS) on photosynthesis in fluctuating irradiance. Leaf gas exchange and chlorophyll fluorescence were measured in leaves exposed to stepwise increases and decreases in irradiance. rwt43, which has a constitutively active Rubisco enzyme in different irradiance intensities (except in darkness), showed faster increases than the wildtype, Colombia-0, in photosynthesis rates after step increases in irradiance. rca-2, having decreased Rca concentration, showed lower rates of increase. In aba2-1, high gs increased the rate of change after stepwise irradiance increases, while in C24, low gs tended to decrease it. Differences in rates of change between Colombia-0 and plants with low levels of NPQ (npq1-2, npq4-1) or SPS (spsa1) were negligible. In Colombia-0, the regulation of Rubisco activation and of gs were therefore limiting for photosynthesis in fluctuating irradiance, while levels of NPQ or SPS were not. This suggests Rca and gs as targets for improvement of photosynthesis of plants in fluctuating irradiance. PMID:27502328

  10. Metabolic and diffusional limitations of photosynthesis in fluctuating irradiance in Arabidopsis thaliana.

    PubMed

    Kaiser, Elias; Morales, Alejandro; Harbinson, Jeremy; Heuvelink, Ep; Prinzenberg, Aina E; Marcelis, Leo F M

    2016-01-01

    A better understanding of the metabolic and diffusional limitations of photosynthesis in fluctuating irradiance can help identify targets for improving crop yields. We used different genotypes of Arabidopsis thaliana to characterise the importance of Rubisco activase (Rca), stomatal conductance (gs), non-photochemical quenching of chlorophyll fluorescence (NPQ) and sucrose phosphate synthase (SPS) on photosynthesis in fluctuating irradiance. Leaf gas exchange and chlorophyll fluorescence were measured in leaves exposed to stepwise increases and decreases in irradiance. rwt43, which has a constitutively active Rubisco enzyme in different irradiance intensities (except in darkness), showed faster increases than the wildtype, Colombia-0, in photosynthesis rates after step increases in irradiance. rca-2, having decreased Rca concentration, showed lower rates of increase. In aba2-1, high gs increased the rate of change after stepwise irradiance increases, while in C24, low gs tended to decrease it. Differences in rates of change between Colombia-0 and plants with low levels of NPQ (npq1-2, npq4-1) or SPS (spsa1) were negligible. In Colombia-0, the regulation of Rubisco activation and of gs were therefore limiting for photosynthesis in fluctuating irradiance, while levels of NPQ or SPS were not. This suggests Rca and gs as targets for improvement of photosynthesis of plants in fluctuating irradiance. PMID:27502328