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https://www.readbyqxmd.com/read/28629515/mutual-cross-talk-between-iron-homeostasis-and-erythropoiesis
#1
Ilona Rybinska, Gaetano Cairo
Iron is necessary for physiological processes essential for the activity of all cells, but the erythropoietic compartment is a privileged iron consumer. In fact, a considerable amount of iron is daily required for hemoglobin synthesis and erythroid cell proliferation. Therefore, a tight link exists between iron metabolism and erythropoiesis. The iron needed for hemoglobin synthesis is mainly ensured by inhibiting hepcidin expression, thereby increasing both ferroportin-mediated iron export from the duodenal absorptive cells and iron release from the reticuloendothelial cells that process old and/or damaged red blood cells...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28629118/long-term-dexamethasone-exposure-down-regulates-hepatic-tfr1-and-reduces-liver-iron-concentration-in-rats
#2
Huifang Li, Shuxia Jiang, Chun Yang, Shu Yang, Bin He, Wenqiang Ma, Ruqian Zhao
Exposure to stress is known to cause hepatic iron dysregulation, but the relationship between prolonged stress and liver iron metabolism is not yet fully understood. Thirty 13-week-old female Sprague-Dawley rats were randomly divided into two groups, as follows: the control group (saline-injection) and the dexamethasone group (Dexamethasone (Dex)-injection 0.1 mg/kg/day). After the 21-day stress trial, the results showed that chronic Dex administration not only impaired serum corticosterone (p = 0.00) and interleukin-6 (IL-6) (p = 0...
June 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28622780/-iron-metabolism
#3
S Vaulont
Iron is an essential trace element ensuring many functions in the body. However, excess iron can be toxic with deleterious consequences on function and tissue integrity. The understanding of the molecular and cellular mechanisms allowing iron level to be kept at physiological concentration has greatly progressed in recent years, in particular with the identification of the iron-regulatory hormone, hepcidin and its receptor ferroportin, the sole iron exporter known to date. This discovery has improved our ability to diagnose and manage iron disorders and offered new therapeutic perspectives for an important class of human diseases...
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28615456/iron-homeostasis-an-anthropocentric-perspective
#4
Richard Coffey, Tomas Ganz
The regulation of iron metabolism in biological systems centers on providing adequate iron for cellular function while limiting iron toxicity. Because mammals cannot excrete iron, mechanisms have evolved to control iron acquisition, storage, and distribution at both systemic and cellular levels. Hepcidin, the master regulator of iron homeostasis, controls iron flows into plasma through inhibition of the sole known mammalian cellular iron exporter ferroportin. Hepcidin is feedback-regulated by iron status, and strongly modulated by inflammation and erythropoietic demand...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615455/minireview-prologue-introduction-metals-in-biology-2017-iron-transport-storage-and-the-ramifications
#5
F Peter Guengerich
In this tenth Thematic Series in Metals in Biology, five Minireviews deal with aspects of iron metabolism. A number of important proteins control iron homeostasis, including hepcidin and ferroportin, in various cells. Other aspects of iron dealt with here include biogenesis of iron-sulfur proteins and chaperones that deliver iron cofactors in cells. Additionally, an iron-regulated metastasis suppressor interacts with the epidermal growth factor receptor and mediates its downstream signaling activity.
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615454/cytosolic-iron-chaperones-proteins-delivering-iron-cofactors-in-the-cytosol-of-mammalian-cells
#6
Caroline C Philpott, Moon-Suhn Ryu, Avery G Frey, Sarju Patel
Eukaryotic cells contain hundreds of metalloproteins that are supported by intracellular systems coordinating the uptake and distribution of metal cofactors. Iron cofactors include heme, iron-sulfur clusters, and simple iron ions. Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperones in the cytosolic/nuclear compartment, binding iron at import and delivering it to enzymes, for storage (ferritin), and export (ferroportin). Ferritin iron is mobilized by autophagy through the cargo receptor, nuclear co-activator 4...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28588503/hepcidin-protects-neuron-from-hemin-mediated-injury-by-reducing-iron
#7
Yu-Fu Zhou, Chao Zhang, Guang Yang, Zhong-Ming Qian, Meng-Wan Zhang, Juan Ma, Fa-Li Zhang, Ya Ke
Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH) and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28534724/maternal-protein-restriction-depresses-the-duodenal-expression-of-iron-transporters-and-serum-iron-level-in-male-weaning-piglets
#8
Wenqiang Ma, Jingyu Lu, Shuxia Jiang, Demin Cai, Shifeng Pan, Yimin Jia, Ruqian Zhao
To investigate the effects of maternal dietary protein restriction on offspring Fe metabolism, twenty-four second-parity Landrace×Yorkshire sows were randomly allocated to standard-protein (SP) and low-protein (LP) groups. The SP sows were fed diets containing 15 and 18 % crude protein throughout pregnancy and lactation, respectively, whereas the LP sows were subjected to 50 % dietary protein restriction. Offspring birth weight was not affected, but the body weight at weaning (P=0·06) and average daily gain (P=0·01) of the female piglets were significantly decreased...
April 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28511389/variability-of-iron-load-in-patients-of-sickle-cell-anaemia-hbss-a-study-from-eastern-india
#9
Pranati Mohanty, Rabindra Kumar Jena, Sudha Sethy
INTRODUCTION: Sickle Cell Anaemia (SCA) is one of the commonest haemoglobinopathies due to a point mutation (A→T) of the β-globin gene. Out of five haplotypes, the Arab-Indian haplotype present in India is one of the least severe phenotype and least studied also. It is characterized by lifelong haemolytic anaemia requiring red cell transfusion leading to iron overload. In contrast, there is very high incidence of deficiency of iron, folic acid and vitamin B12. AIM: Our objective was to access the Iron status of SCA patients and to find its correlation with various parameters like red cell transfusion, haemolysis and serum hepcidin...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507548/iron-and-hepcidin-independent-downregulation-of-the-iron-exporter-ferroportin-in-macrophages-during-salmonella-infection
#10
Alexandra Willemetz, Sean Beatty, Etienne Richer, Aude Rubio, Anne Auriac, Ruth J Milkereit, Olivier Thibaudeau, Sophie Vaulont, Danielle Malo, François Canonne-Hergaux
Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and downregulation of the iron exporter ferroportin (FPN) is thought to participate in the establishment of anemia of inflammation after infection. However, an upregulation of FPN has been proposed to limit macrophages iron access to intracellular pathogens. Therefore, we studied the iron homeostasis and in particular the regulation of FPN after infection with Salmonella enterica serovar Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp(-/-)) levels...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28502703/cell-death-induced-by-mitochondrial-complex-i-inhibition-is-mediated-by-iron-regulatory-protein-1
#11
Pamela J Urrutia, Pabla Aguirre, Victoria Tapia, Carlos M Carrasco, Natalia P Mena, Marco T Núñez
Mitochondrial dysfunction and oxidative damage, often accompanied by elevated intracellular iron levels, are pathophysiological features in a number of neurodegenerative processes. The question arises as to whether iron dyshomeostasis is a consequence of mitochondrial dysfunction. Here we have evaluated the role of Iron Regulatory Protein 1 (IRP1) in the death of SH-SY5Y dopaminergic neuroblastoma cells subjected to mitochondria complex I inhibition. We found that complex I inhibition was associated with increased levels of transferrin receptor 1 (TfR1) and iron uptake transporter divalent metal transporter 1 (DMT1), and decreased levels of iron efflux transporter Ferroportin 1 (FPN1), together with increased (55)Fe uptake activity and an increased cytoplasmic labile iron pool...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28501597/reciprocal-regulation-between-hepcidin-and-erythropoiesis-and-its-therapeutic-application-in-erythroid-disorders
#12
REVIEW
Caiyi Wang, Zheng Fang, Zesen Zhu, Jing Liu, Huiyong Chen
Iron is required for hemoglobin production, and it plays a key role during erythropoiesis. Systemic iron homeostasis is mainly negatively regulated by the peptide hormone hepcidin, coded by the gene HAMP. Hepcidin excess may cause iron deficiency, iron-restricted erythropoiesis, and anemia. Conversely, hepcidin insufficiency leads to iron overload and oxidative damage in multiple tissues. During regulation of hepcidin synthesis, multiple promoter elements in the HAMP gene respond to variable signaling pathways corresponding to different extracellular situations...
May 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28499927/disruption-of-the-hepcidin-ferroportin-regulatory-system-causes-pulmonary-iron-overload-and-restrictive-lung-disease
#13
Joana Neves, Dominik Leitz, Simone Kraut, Christina Brandenberger, Raman Agrawal, Norbert Weissmann, Christian Mühlfeld, Marcus A Mall, Sandro Altamura, Martina U Muckenthaler
Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s) involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1(C326S)), increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells...
April 29, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28495746/restored-iron-transport-by-a-small-molecule-promotes-absorption-and-hemoglobinization-in-animals
#14
Anthony S Grillo, Anna M SantaMaria, Martin D Kafina, Alexander G Cioffi, Nicholas C Huston, Murui Han, Young Ah Seo, Yvette Y Yien, Christopher Nardone, Archita V Menon, James Fan, Dillon C Svoboda, Jacob B Anderson, John D Hong, Bruno G Nicolau, Kiran Subedi, Andrew A Gewirth, Marianne Wessling-Resnick, Jonghan Kim, Barry H Paw, Martin D Burke
Multiple human diseases ensue from a hereditary or acquired deficiency of iron-transporting protein function that diminishes transmembrane iron flux in distinct sites and directions. Because other iron-transport proteins remain active, labile iron gradients build up across the corresponding protein-deficient membranes. Here we report that a small-molecule natural product, hinokitiol, can harness such gradients to restore iron transport into, within, and/or out of cells. The same compound promotes gut iron absorption in DMT1-deficient rats and ferroportin-deficient mice, as well as hemoglobinization in DMT1- and mitoferrin-deficient zebrafish...
May 12, 2017: Science
https://www.readbyqxmd.com/read/28464091/effect-of-iron-source-on-iron-absorption-and-gene-expression-of-iron-transporters-in-the-ligated-duodenal-loops-of-broilers
#15
L Y Zhang, X F Li, X D Liao, L Y Zhang, L Lu, X G Luo
This experiment was conducted to investigate the effect of iron source on Fe absorption and the gene expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1) in the ligated duodenal loops of broilers. The in situ ligated duodenal loops from Fe-deficient broiler chicks (28-d-old) were perfused with Fe solutions containing 0 to 14.33 mmol Fe/L from 1 of the following: Fe sulfate (FeSO∙7HO), Fe methionine with weak chelation strength (Fe-Met W; chelation strength is expressed as quotient of formation [Q] value, Q = 1...
April 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28462381/ferroportin-is-essential-for-iron-absorption-during-suckling-%C3%A2-but%C3%A2-is-hyporesponsive-to-the-regulatory-hormone%C3%A2-hepcidin
#16
David M Frazer, Sarah J Wilkins, Deepak Darshan, Cornel S G Mirciov, Linda A Dunn, Gregory J Anderson
BACKGROUND & AIMS: Previous studies have suggested that iron absorption in suckling mammals is refractory to stimuli that normally would decrease absorption in adults. To better understand the regulation of iron absorption during suckling, we have characterized the relationship between hepcidin, ferroportin, and iron absorption at this crucial stage of life. METHODS: To determine whether ferroportin is involved in iron absorption during suckling, absorption was measured in intestine-specific ferroportin knockout mice...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28450059/epidermal-iron-metabolism-for-iron-salvage
#17
Masayuki Asano, Kenshi Yamasaki, Takashi Yamauchi, Tadashi Terui, Setsuya Aiba
BACKGROUND: The epidermis shows a reverse iron gradient from the basal layer to the stratum corneum and consequently, little epidermal intracellular iron is lost by desquamation. OBJECTIVE: To clarify the underlying mechanism of iron salvage. METHODS: We first used immunohistochemistry and mRNA quantification to demonstrate the distinctive expression pattern of iron metabolism molecules. The obtained results were confirmed using normal human epidermal keratinocytes (NHEKs) during in vitro differentiation...
April 14, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28426710/change-in-iron-metabolism-in-rats-after-renal-ischemia-reperfusion-injury
#18
Guang-Liang Xie, Lin Zhu, Yan-Min Zhang, Qian-Nan Zhang, Qing Yu
Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1) and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI). In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI...
2017: PloS One
https://www.readbyqxmd.com/read/28414228/molecular-aspects-of-a-robust-assay-for-ferroxidase-function-of-ceruloplasmin
#19
Laura Cortes, Blaine R Roberts, Anthony G Wedd, Zhiguang Xiao
Ceruloplasmin (Cp) is one of the most complex multicopper oxidase enzymes and plays an essential role in the metabolism of iron in mammals. Ferrous ion supplied by the ferroportin exporter is converted by Cp to ferric ion that is accepted by plasma metallo-chaperone transferrin. Study of the enzyme at the atomic and molecular level has been hampered by the lack of a suitable ferrous substrate. We have developed the classic chromophoric complex Fe(II)Hx(Tar)2 (H2Tar, 4-(2-thiazolylazo)resorcinol; x = 0-2; overall charge omitted) as a robust substrate for evaluation of the ferroxidase function of Cp and related enzymes...
April 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28361857/artemisinin-modulating-effect-on-human-breast-cancer-cell-lines-with-different-sensitivity-to-cytostatics
#20
V F Chekhun, N Yu Lukianova, T V Borikun, T V Zadvorny, A Mokhir
AIM: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin - Dox; cisplatin - DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. MATERIALS AND METHODS: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid...
March 2017: Experimental Oncology
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