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Iron homeostasis

IJsbrand T Klip, Adriaan A Voors, Dorine W Swinkels, Stephan J L Bakker, Jenny E Kootstra-Ros, Carolyn S Lam, Pim van der Harst, Dirk J van Veldhuisen, Peter van der Meer
AIMS: Heart failure (HF) is a common manifestation of patients with primary and secondary causes of iron overload, whereas in patients with established HF iron deficiency impairs outcome. Whether iron stores, either depleted or in overload, amplify the risk for new-onset HF among healthy individuals is unknown. The present study aimed to assess whether markers of iron status or the iron-regulatory hormone hepcidin are associated with new-onset HF or cardiovascular (CV) events in the general population...
October 19, 2016: European Journal of Heart Failure
Antonino Baez, Joseph Shiloach
The damaging effect of high oxygen concentration on growth of Escherichia coli is well established. Over-oxygenation increases the intracellular concentration of reactive oxygen species (ROS), causing the destruction of the [4Fe-4S] cluster of dehydratases and limiting the biosynthesis of both branched-chain amino acids and nicotinamide adenine dinucleotide. A key enzyme that reduces the damaging effect of superoxide is superoxide dismutase (SOD). Its transcriptional regulation is controlled by global transcription regulators that respond to changes in oxygen and iron concentrations and pH...
October 18, 2016: Antonie Van Leeuwenhoek
Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios G Papavassiliou, Hippokratis Kiaris
Pancreatic dysfunction during diabetes is linked to the induction of endoplasmic reticulum (ER) stress on pancreatic beta (β) cells. Our laboratory recently discovered that p21 protects from diabetes by modifying the outcome of ER stress response. In the present study, we explored the antidiabetic activity of ciclopirox (CPX), an iron chelator and recently described activator of p21 expression. The effects of CPX in beta cell survival and function were assessed in cultured islets in vitro as well as in diabetic mice in vivo...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
K Nakamura, M Sakurai, Y Morikawa, S Y Nagasawa, K Miura, M Ishizaki, T Kido, Y Naruse, M Nakashima, K Nogawa, Y Suwazono, H Nakagawa
Objectives: The present cohort study investigated the relationship between serum ferritin levels and indices of insulin resistance and β-cell dysfunction in a normoglycemic population without iron overload disorders. Methods: The study participants included 575 normoglycemic Japanese men aged 35-57 years with serum ferritin levels of 400 μg/L or less. Insulin resistance and β-cell dysfunction were estimated at baseline and after 3 years by the homeostasis model assessments of insulin resistance and β-cell function (HOMA-IR and HOMA-β, respectively)...
October 17, 2016: Experimental and Clinical Endocrinology & Diabetes
Pavlína Hašková, Hana Jansová, Jan Bureš, Miloslav Macháček, Anna Jirkovská, Katherine J Franz, Petra Kovaříková, Tomáš Šimůnek
Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis...
October 12, 2016: Toxicology
Mariia Lunova, Peggy Schwarz, Renwar Nuraldeen, Kateryna Levada, Deniz Kuscuoglu, Michael Stützle, Maja Vujic, Johannes Haybaeck, Piotr Ruchala, Milan Jirsa, Jean-Christophe Deschemin, Sophie Vaulont, Christian Trautwein, Pavel Strnad
Iron is both an essential and a potentially toxic element and its systemic homeostasis is controlled by the iron-hormone hepcidin. Hepcidin binds to the cellular iron exporter ferroportin, causes its degradation and thereby diminishes iron uptake from the intestine and the release of iron from macrophages. Given that hepcidin-resistant ferroportin mutant mice display exocrine pancreas dysfunction, we analysed pancreata of aging hepcidin knockout mice (KOs). Hepcidin and Hfe KOs were compared to wild type animals (WTs) kept on standard or iron-rich diets...
October 14, 2016: Journal of Pathology
Gianpiero Vigani, Dario Di Silvestre, Anna Maria Agresta, Silvia Donnini, Pierluigi Mauri, Christian Gehl, Florian Bittner, Irene Murgia
Molybdenum (Mo) and iron (Fe) are essential micronutrients required for crucial enzyme activities in plant metabolism. Here we investigated the existence of a mutual control of Mo and Fe homeostasis in cucumber (Cucumis sativus). Plants were grown under single or combined Mo and Fe starvation. Physiological parameters were measured, the ionomes of tissues and the ionomes and proteomes of root mitochondria were profiled, and the activities of molybdo-enzymes and the synthesis of molybdenum cofactor (Moco) were evaluated...
October 13, 2016: New Phytologist
Upendarrao Golla, Deepthi Joseph, Raghuvir Singh Tomar
Valproic acid (VA) is a pharmacologically important histone deacetylase inhibitor that recently garnered attention as an anticancer agent. Since the molecular mechanisms behind the multiple effects of VA are unclear, this study was aimed to unravel the comprehensive cellular processes affected by VA and its molecular targets in vivo using budding yeast as a model organism. Interestingly, genome-wide transcriptome analysis of cells treated with VA showed differential regulation of 30% of the genome. Functional enrichment analysis of VA transcriptome evidenced alteration of various cellular processes including cell cycle, cell wall biogenesis, DNA repair, ion homeostasis, metabolism, stress response, transport and ribosomal biogenesis, etc...
October 13, 2016: Scientific Reports
Amanda M V Brown, Sulochana K Wasala, Dana K Howe, Amy B Peetz, Inga A Zasada, Dee R Denver
Wolbachia, one of the most widespread endosymbionts, is a target for biological control of mosquito-borne diseases (malaria and dengue virus), and antibiotic elimination of infectious filarial nematodes. We sequenced and analyzed the genome of a new Wolbachia strain (wPpe) in the plant-parasitic nematode Pratylenchus penetrans. Phylogenomic analyses placed wPpe as the earliest diverging Wolbachia, suggesting two evolutionary invasions into nematodes. The next branches comprised strains in sap-feeding insects, suggesting Wolbachia may have first evolved as a nutritional mutualist...
October 13, 2016: Scientific Reports
Katarzyna Sikorska, Agnieszka Bernat, Anna Wroblewska
BACKGROUND: The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression...
October 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Yuping Li, Ke Pan, Lin Chen, Jiao-Lin Ning, Xiaojun Li, Ting Yang, Niccolò Terrando, Jianteng Gu, Guocai Tao
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function. METHODS: A model of laparotomy under general anesthesia and analgesia was used to study POCD...
October 12, 2016: Journal of Neuroinflammation
Pia Rantakari, Norma Jäppinen, Emmi Lokka, Elias Mokkala, Heidi Gerke, Emilia Peuhu, Johanna Ivaska, Kati Elima, Kaisa Auvinen, Marko Salmi
Macrophages are required for normal embryogenesis, tissue homeostasis and immunity against microorganisms and tumours. Adult tissue-resident macrophages largely originate from long-lived, self-renewing embryonic precursors and not from haematopoietic stem-cell activity in the bone marrow. Although fate-mapping studies have uncovered a great amount of detail on the origin and kinetics of fetal macrophage development in the yolk sac and liver, the molecules that govern the tissue-specific migration of these cells remain completely unknown...
October 12, 2016: Nature
Lisa Gasperini, Elisa Meneghetti, Giuseppe Legname, Federico Benetti
Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors...
2016: Frontiers in Neuroscience
Vandana Sharma, Rajaram Purushotham, Rupinder Kaur
The phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival and virulence in the pathogenic yeast Candida glabrata Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA-sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption...
October 11, 2016: Journal of Biological Chemistry
Gaetano Bergamaschi, Antonio Di Sabatino, Alessandra Pasini, Cristina Ubezio, Filippo Costanzo, Davide Grataroli, Michela Masotti, Costanza Alvisi, Gino R Corazza
BACKGROUND & AIMS: Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin...
September 30, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Rachel Waller, M Nicola Woodroofe, Stephen B Wharton, Paul G Ince, Simona Francese, Paul R Heath, Alex Cudzich-Madry, Ruth H Thomas, Natalie Rounding, Basil Sharrack, Julie E Simpson
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). White matter lesions in MS are surrounded by areas of non-demyelinated normal appearing white matter (NAWM) with complex pathology, including blood brain barrier dysfunction, axonal damage and glial activation. Astrocytes, the most abundant cell type within the CNS, may respond and/or contribute to lesion pathogenesis. We aimed to characterise the transcriptomic profile of astrocytes in NAWM to determine whether specific glial changes exist in the NAWM which contribute to lesion development or prevent disease progression...
October 15, 2016: Journal of Neuroimmunology
Kourosh Honarmand Ebrahimi, Eckhard Bill, Peter-Leon Hagedoorn, Wilfred R Hagen
Ferritin is a nanocage protein made of 24 subunits. Its major role is to manage intracellular concentrations of free Fe(ii) and Fe(iii) ions, which is pivotal for iron homeostasis across all domains of life. This function of the protein is regulated by a conserved di-iron catalytic center and has been the subject of extensive studies over the past 50 years. Yet, it has not been fully understood how Fe(ii) is oxidized in the di-iron catalytic center and it is not known why eukaryotic and microbial ferritins oxidize Fe(ii) with different kinetics...
September 29, 2016: Molecular BioSystems
Hans-Jörg Mai, Stéphanie Pateyron, Petra Bauer
BACKGROUND: FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes...
October 3, 2016: BMC Plant Biology
Yue Cao, Hao Ai, Ajay Jain, Xueneng Wu, Liang Zhang, Wenxia Pei, Aiqun Chen, Guohua Xu, Shubin Sun
BACKGROUND: Phosphorus (P), an essential macronutrient, is often limiting in soils and affects plant growth and development. In Arabidopsis thaliana, Low Phosphate Root1 (LPR1) and its close paralog LPR2 encode multicopper oxidases (MCOs). They regulate meristem responses of root system to phosphate (Pi) deficiency. However, the roles of LPR gene family in rice (Oryza sativa) in maintaining Pi homeostasis have not been elucidated as yet. RESULTS: Here, the identification and expression analysis for the homologs of LPR1/2 in rice were carried out...
October 3, 2016: BMC Plant Biology
Jung-Heun Ha, Caglar Doguer, James F Collins
Intestinal iron absorption is highly regulated since no mechanism for iron excretion exists. We previously demonstrated that expression of an intestinal copper transporter (Atp7a) increases in parallel with genes encoding iron transporters in the rat duodenal epithelium during iron deprivation (Am. J. Physiol.: Gastrointest. Liver Physiol., 2005, 288, G964-G971). This led us to postulate that Atp7a may influence intestinal iron flux. Therefore, to test the hypothesis that Atp7a is required for optimal iron transport, we silenced Atp7a in rat IEC-6 and human Caco-2 cells...
September 1, 2016: Metallomics: Integrated Biometal Science
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