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Iron homeostasis

Wesley Hayes
Anemia is a common complication of chronic kidney disease (CKD) in children, and dysregulation of iron homeostasis plays a central role in its pathogenesis. Optimizing iron status is a prerequisite for effective treatment of anemia. Insufficient iron can lead to inappropriate escalation of the erythropoiesis-stimulating agent (ESA) dose, which is associated with adverse outcomes. Excess iron supplementation also has negative sequelae including free radical tissue damage and increased risk of systemic infection...
April 17, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Ioana M Abbas, Holger Hoffmann, María Montes-Bayón, Michael G Weller
Mass spectrometry-based methods play a crucial role in the quantification of the main iron metabolism regulator hepcidin by singling out the bioactive 25-residue peptide from the other naturally occurring N-truncated isoforms (hepcidin-20, -22, -24), which seem to be inactive in iron homeostasis. However, several difficulties arise in the MS analysis of hepcidin due to the "sticky" character of the peptide and the lack of suitable standards. Here, we propose the use of amino- and fluoro-silanized autosampler vials to reduce hepcidin interaction to laboratory glassware surfaces after testing several types of vials for the preparation of stock solutions and serum samples for isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)...
April 18, 2018: Analytical and Bioanalytical Chemistry
Lyla A Youssef, Abdelhadi Rebbaa, Sergey Pampou, Stuart P Weisberg, Brent R Stockwell, Eldad A Hod, Steven L Spitalnik
Macrophages play important roles in recycling iron derived from the clearance of red blood cells (RBCs). They are also a critically important component of host defense, protecting against invading pathogens. However, the effects on macrophage biology of acutely ingesting large numbers of RBCs are not completely understood. To investigate this issue, we used a mouse model of RBC transfusion and clearance, which mimics the clinical setting. In this model, transfusions of refrigerator storage-damaged (i.e., "old") RBCs led to increased erythrophagocytosis by splenic red pulp macrophages (RPMs)...
April 17, 2018: Blood
Jiashuo Zheng, Ruiwei Jiang, Min Chen, Zaitunamu Maimaitiming, Junzhuo Wang, Gregory J Anderson, Chris D Vulpe, Joshua L Dunaief, Huijun Chen
Background: The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear. Objective: The aim was to study the role of MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were generated by crossing both single KO mice...
April 1, 2018: Journal of Nutrition
Michael J Pascoe, Jiraporn Lueangsakulthai, Delia Ripley, Roger H Morris, Sarah E Maddocks
Hepcidin belongs to the antimicrobial peptide family but has weak activity with regards to bacterial killing. The regulatory function of hepcidin in humans serves to maintain an iron-restricted environment that limits the growth of pathogens; this study explored whether hepcidin affected bacterial iron homeostasis and oxidative stress using the model organism Escherichia coli. Using the Miller assay it was determined that under low iron availability exposure to sub-inhibitory doses of hepcidin (4 -12μM) led to 2-fold and 4-fold increases in the expression of ftnA and bfd respectively (p < 0...
April 6, 2018: FEMS Microbiology Letters
Isaac J Carney, Jacek L Kolanowski, Zelong Lim, Benjamin Chekroun, Angela G Torrisi, Trevor W Hambley, Elizabeth J New
Iron dysregulation is implicated in numerous diseases, and iron homeostasis is profoundly influenced by the labile iron pool (LIP). Tools to easily observe changes in the LIP are limited, with calcein AM-based assays most widely used. We describe here FlCFe1, a ratiometric analogue of calcein AM, which also provides the capacity for imaging iron in 3D cell models.
April 16, 2018: Metallomics: Integrated Biometal Science
Lin Zhang, Guangjie Li, Meng Wang, Dongwei Di, Li Sun, Herbert J Kronzucker, Weiming Shi
The root tip zone is regarded as the principal action site for iron (Fe) toxicity and is more sensitive than other root zones, but the mechanism underpinning this remains largely unknown. We explored the mechanism underpinning the higher sensitivity at the Arabidopsis root tip and elucidated the role of nitric oxide (NO) using NO-related mutants and pharmacological methods. Higher Fe sensitivity of the root tip is associated with reduced potassium (K+ ) retention. NO in root tips is increased significantly above levels elsewhere in the root and is involved in the arrest of primary root tip zone growth under excess Fe, at least in part related to NO-induced K+ loss via SNO1 (sensitive to nitric oxide 1)/SOS4 (salt overly sensitive 4) and reduced root tip zone cell viability...
April 15, 2018: New Phytologist
Emmanuel Pourcelot, Marine Lénon, Peggy Charbonnier, Fiona Louis, Pascal Mossuz, Jean-Marc Moulis
In animal cells the specific translational control of proteins contributing to iron homeostasis is mediated by the interaction between the Iron Regulatory Proteins (IRP1 and IRP2) and the Iron Responsive Elements (IRE) located in the untranslated regions (UTR) of regulated messengers, such as those encoding ferritin or the transferrin receptor. The absolute concentrations of the components of this regulatory system in hematopoietic cells and the ability of the endogenous IRP to regulate exogenous IRE have been measured...
April 13, 2018: Metallomics: Integrated Biometal Science
Roberta Olmo Pinheiro, Veronica Schmitz, Bruno Jorge de Andrade Silva, André Alves Dias, Beatriz Junqueira de Souza, Mayara Garcia de Mattos Barbosa, Danuza de Almeida Esquenazi, Maria Cristina Vidal Pessolani, Euzenir Nunes Sarno
Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae . Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease...
2018: Frontiers in Immunology
Elisabeth Tamayo, Simon A B Knight, Ascensión Valderas, Andrew Dancis, Nuria Ferrol
Arbuscular mycorrhizal (AM) fungi can improve iron (Fe) acquisition of their host plants. Here, we report a characterization of two components of the high-affinity reductive Fe uptake system of Rhizophagus irregularis, the ferric reductase (RiFRE1) and the high affinity Fe permeases (RiFTR1-2). In the extraradical mycelia (ERM), Fe deficiency induced activation of a plasma membrane-localized ferric reductase, an enzyme that reduces Fe(III) sources to the more soluble Fe(II). Yeast mutant complementation assays showed that RiFRE1 encodes a functional ferric reductase and RiFTR1 an iron permease...
April 6, 2018: Environmental Microbiology
Marcos Caballero-Molada, María D Planes, Helena Benlloch, Sergio Atares, Miguel A Naranjo, Ramón Serrano
In eukaryotic cells amino acid biosynthesis is feedback inhibited by amino acids through inhibition of conserved protein kinase Gcn2. This decreases phosphorylation of initiation factor eIF2a resulting in general activation of translation but inhibition of translation of mRNA for transcription factor (TF) Gcn4 in yeast or ATF4 in mammals. These TFs are positive regulators of amino acid biosynthetic genes. As several enzymes of amino acid biosynthesis contain iron-sulfur clusters and iron excess is toxic, iron and amino acid homeostasis should be coordinated...
April 6, 2018: Biochemical Journal
Dalel Askri, Souhir Ouni, Said Galai, Josiane Arnaud, Benoit Chovelon, Sylvia G Lehmann, Nathalie Sturm, Mohsen Sakly, Michel Sève, Salem Amara
Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis...
April 5, 2018: Environmental Science and Pollution Research International
Andrew Elohim Elohim Laloo, Justin Wei, Dongbo Wang, Shaman Narayanasamy, Inka Vanwonterghem, David W Waite, Jason Steen, Anne Kaysen, Anna Heintz-Buschart, Qilin Wang, Benjamin L Schulz, Amanda S Nouwens, Paul Wilmes, Philip Hugenholtz, Zhiguo Yuan, Philip L Bond
Free Nitrous Acid (FNA) exerts a broad range of antimicrobial effects on bacteria although susceptibility varies considerably amongst microorganisms. Among nitrifiers found in activated sludge of wastewater treatment processes (WWTP), nitrite oxidising bacteria (NOB) are more susceptible to FNA compared to ammonia oxidising bacteria (AOB). This selective inhibition of NOB over AOB in WWTP bypasses nitrate production and improves the efficiency and costs of the nitrogen removal process in both the activated sludge and anaerobic ammonium oxidation (Anammox) system...
April 5, 2018: Environmental Science & Technology
Ma Teresa Pellicer Martinez, Ana Bermejo Martinez, Jason C Crack, John D Holmes, Dimitri A Svistunenko, Andrew W B Johnston, Myles R Cheesman, Jonathan D Todd, Nick E Le Brun
Rhizobial iron regulator A (RirA) is a global regulator of iron homeostasis in many nitrogen-fixing Rhizobia and related species of α-proteobacteria. It belongs to the widespread Rrf2 super-family of transcriptional regulators and features three conserved Cys residues that characterise the binding of an iron-sulfur cluster in other Rrf2 family regulators. Here we report biophysical studies demonstrating that RirA contains a [4Fe-4S] cluster, and that this form of the protein binds RirA-regulated DNA, consistent with its function as a repressor of expression of many genes involved in iron uptake...
December 1, 2017: Chemical Science
Frank Bienaimé, Ariane Ambolet, Béatrice Aussilhou, François Brazier, Marie Fouchard, Amandine Viau, Pauline Barre, Anne-Marie Tissier, Jean-Michel Correas, Valérie Paradis, Fabiola Terzi, Gérard Friedlander, Bertrand Knebelmann, Dominique Joly, Dominique Prié
Context: the bone-derived hormone fibroblast growth factor 23 (FGF23) controls phosphate homeostasis and urinary phosphate excretion. FGF23 plasma levels increase at the early step of renal insufficiency to prevent hyperphosphatemia. Recent evidence suggests that this increase has off-target effects on cardiac and immune cells that compromises patients' health. Subjects with autosomal dominant polycystic kidney disease (ADPKD) have been reported to display higher FGF23 concentrations than non-ADPKD patients with similar renal function...
March 29, 2018: Journal of Clinical Endocrinology and Metabolism
Ana Gaspar-Cordeiro, Soraia M Caetano, Catarina Amaral, Claudina Rodrigues-Pousada, Catarina Pimentel
In the yeast Saccharomyces cerevisiae Aft1, the low iron-sensing transcription factor is known to regulate the expression of the FET3 gene. However, we found that a strain lacking FET3 is more sensitive to copper excess than a strain lacking AFT1 and accordingly, FET3 expression is not fully compromised in the latter. These findings suggest that under such conditions another regulator comes into play and controls FET3 expression. In this work we identify Ace1, the regulator of copper-detoxification genes, as a regulator of FET3...
March 31, 2018: FEBS Journal
Paola Punzo, Alessandra Ruggiero, Marco Possenti, Roberta Nurcato, Antonello Costa, Giorgio Morelli, Stefania Grillo, Giorgia Batelli
Modulation of growth in response to environmental cues is a fundamental aspect of plant adaptation to abiotic stresses. TIP41 (TAP42 INTERACTING PROTEIN OF 41 kDa) is the Arabidopsis thaliana orthologue of proteins isolated in mammals and yeast that participate in the Target-of-Rapamycin (TOR) pathway, which modifies cell growth in response to nutrient status and environmental conditions. Here, we characterized the function of TIP41 in Arabidopsis. Expression analyses showed that TIP41 is constitutively expressed in vascular tissues, and is induced following long-term exposure to NaCl, PEG and ABA, suggesting a role of TIP41 in adaptation to abiotic stress...
March 30, 2018: Plant Journal: for Cell and Molecular Biology
Iga M Stasiak, Dale A Smith, Tomas Ganz, Graham J Crawshaw, Jutta D Hammermueller, Dorothee Bienzle, Brandon N Lillie
Hepcidin is the key regulator of iron homeostasis in the body. Iron storage disease (hemochromatosis) is a frequent cause of liver disease and mortality in captive Egyptian fruit bats (Rousettus aegyptiacus), but reasons underlying this condition are unknown. Hereditary hemochromatosis in humans is due to deficiency of hepcidin or resistance to the action of hepcidin. Here, we investigated the role of hepcidin in iron metabolism in one species of pteropodid bat that is prone to iron storage disease [Egyptian fruit bat (with and without hemochromatosis)], one species of pteropodid bat where iron storage disease is rare [straw-colored fruit bat (Eidolon helvum)], and one species of bat with a natural diet very high in iron, in which iron storage disease is not reported [common vampire bat (Desmodus rotundus)]...
March 29, 2018: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Azhaar Ashraf, Maryam Clark, Po-Wah So
Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases...
2018: Frontiers in Aging Neuroscience
Christopher R Chitambar, Mona M Al-Gizawiy, Hisham S Alhajala, Kimberly R Pechman, Janine P Wereley, Robert Wujek, Paul A Clark, John S Kuo, William E Antholine, Kathleen M Schmainda
Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMECs) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSCs) lines express TfRs and that their growth is inhibited by gallium maltolate (GaM) in vitro...
March 28, 2018: Molecular Cancer Therapeutics
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