Intracellular Iron Metabolism

2015 ◽  
pp. 148-152 ◽  
Author(s):  
Jim Drysdale ◽  
Isabelle Dugast ◽  
Panos Papadopoulos ◽  
Elisabetta Zappone
Keyword(s):  
Iron Metabolism ◽  
Intracellular Iron

scholarly journals Effect of nitric oxide on expression of transferrin receptor and ferritin and on cellular iron metabolism in K562 human erythroleukemia cells

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2962-2966 ◽  
Author(s):  
R Oria ◽  
L Sanchez ◽  
T Houston ◽  
MW Hentze ◽  
FY Liew ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Iron Metabolism ◽  
Transferrin Receptor ◽  
Regulatory Protein ◽  
Inhibitory Effect ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Intracellular Iron ◽  
Cellular Iron ◽  
Erythroleukemia Cells

Nitric oxide (NO) is known to increase the affinity of the intracellular iron-regulatory protein (IRP) for iron-response elements (IREs) in transferrin receptor and ferritin mRNAs, suggesting that it may act as a regulator of cellular iron metabolism. In this study, exogenous NO produced by adding the NO-generator S-nitroso-N-acetyl penicillamine gave a dose-dependent upregulation of transferrin receptor expression by K562 erythroleukemia cells and increased levels of transferrin receptor mRNA. NO did not affect the affinity of transferrin binding by the transferrin receptor. NO alone did not alter intracellular ferritin levels, but it did abrogate the inhibitory effect of the iron chelator desferrioxamine and potentiated the stimulatory effect of additional iron. NO also caused some increase in ferritin mRNA levels, which might mask any IRP-/IRE-mediated inhibitory effect of NO on ferritin translation. Although NO did not affect net iron uptake, it increased release of iron from K562 cells pulsed previously with 59Fe, and subcellular fractionation showed that it also increased the proportion of intracellular iron bound to ferritin. These findings provide direct evidence that NO can affect cellular iron metabolism and suggest that NO produced in vivo by activated bone marrow macrophages might affect erythropoiesis.

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

Tumor Biology ◽  
2017 ◽  
Vol 39 (10) ◽  
pp. 101042831772618 ◽  
Author(s):  
Khuloud Bajbouj ◽  
Jasmin Shafarin ◽  
Maher Y Abdalla ◽  
Iman M Ahmad ◽  
Mawieh Hamad
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Iron Metabolism ◽  
Membrane Damage ◽  
Intracellular Iron ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals Linking Cancer Metabolic Dysfunction and Genetic Instability through the Lens of Iron Metabolism

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1077 ◽  
Author(s):  
Michael S. Petronek ◽  
Douglas R. Spitz ◽  
Garry R. Buettner ◽  
Bryan G. Allen
Keyword(s):  
Dna Damage ◽  
Steady State ◽  
Cancer Cells ◽  
Iron Metabolism ◽  
Genetic Instability ◽  
Cellular Proliferation ◽  
Intracellular Iron ◽  
Iron Regulatory Proteins ◽  
Wide Range ◽  
Labile Iron

Iron (Fe) is an essential element that plays a fundamental role in a wide range of cellular functions, including cellular proliferation, DNA synthesis, as well as DNA damage and repair. Because of these connections, iron has been strongly implicated in cancer development. Cancer cells frequently have changes in the expression of iron regulatory proteins. For example, cancer cells frequently upregulate transferrin (increasing uptake of iron) and down regulate ferroportin (decreasing efflux of intracellular iron). These changes increase the steady-state level of intracellular redox active iron, known as the labile iron pool (LIP). The LIP typically contains approximately 2% intracellular iron, which primarily exists as ferrous iron (Fe2+). The LIP can readily contribute to oxidative distress within the cell through Fe2+-dioxygen and Fenton chemistries, generating the highly reactive hydroxyl radical (HO•). Due to the reactive nature of the LIP, it can contribute to increased DNA damage. Mitochondrial dysfunction in cancer cells results in increased steady-state levels of hydrogen peroxide and superoxide along with other downstream reactive oxygen species. The increased presence of H2O2 and O2•− can increase the LIP, contributing to increased mitochondrial uptake of iron as well as genetic instability. Thus, iron metabolism and labile iron pools may play a central role connecting the genetic mutational theories of cancer to the metabolic theories of cancer.

Trypanosoma brucei vacuolar protein sorting 41 (VPS41) is required for intracellular iron utilization and maintenance of normal cellular morphology

Parasitology ◽  
2007 ◽  
Vol 134 (11) ◽  
pp. 1639-1647 ◽  
Author(s):  
S. LU ◽  
T. SUZUKI ◽  
N. IIZUKA ◽  
S. OHSHIMA ◽  
Y. YABU ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Iron Metabolism ◽  
Protein Sorting ◽  
Tsetse Fly ◽  
Cellular Morphology ◽  
Yeast Cells ◽  
Intracellular Iron ◽  
Procyclic Form ◽  
Vacuolar Protein ◽  
Iron Utilization

SUMMARYProcyclic forms of Trypanosoma brucei brucei remain and propagate in the midgut of tsetse fly where iron is rich. Additional iron is also required for their growth in in vitro culture. However, little is known about the genes involved in iron metabolism and the mechanism of iron utilization in procyclic-form cells. Therefore, we surveyed the genes involved in iron metabolism in the T. b. brucei genome sequence database. We found a potential homologue of vacuole protein sorting 41 (VPS41), a gene that is required for high-affinity iron transport in Saccharomyces cerevisiae and cloned the full-length gene (TbVPS41). Complementation analysis of TbVPS41 in ΔScvps41 yeast cells showed that TbVPS41 could partially suppress the inability of ΔScvps41 yeast cells to grow on low-iron medium, but it could not suppress the fragmented vacuole phenotype. Further RNA interference (RNAi)-mediated gene knock-down in procyclic-form cells resulted in a significant reduction of growth in low-iron medium; however, no change in growth was observed in normal culture medium. Transmission electron microscopy showed that RNAi caused T. b. brucei cells to have larger numbers of small intracellular vesicles, similar to the fragmented vacuoles observed in ΔScvps41 yeast cells. The present study demonstrates that TbVPS41 plays an important role in the intracellular iron utilization system as well as in the maintenance of normal cellular morphology.

scholarly journals Iron metabolism in the Belgrade rat

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 623-628 ◽  
Author(s):  
J Edwards ◽  
H Huebers ◽  
C Kunzler ◽  
C Finch
Keyword(s):  
Iron Metabolism ◽  
Iron Uptake ◽  
Iron Concentration ◽  
Release Mechanism ◽  
Iron Release ◽  
Intracellular Iron ◽  
Plasma Iron ◽  
Body Tissues ◽  
Erythroid Hyperplasia ◽  
Iron Deficient

Iron metabolism in the Belgrade rat was examined in the intact animal and in the reticulocyte suspensions. The plasma iron turnover was increased. However, when allowance was made for the effect of the elevated plasma iron concentration, erythroid marrow capacity for iron uptake was at basal levels. Numbers of erythroid cells in marrow and spleen measured by the radioiron dilution technique were increased. Thus iron uptake was not proportionate to the erythroid hyperplasia in the b/b rat, despite a more than adequate plasma iron supply. This relative deficiency in iron uptake was reflected in a severe microcytosis and elevated red cell protoporphyrin. Reticulocyte incubation studies demonstrated an unimpaired uptake of the transferrin- iron-receptor complex but a marked reduction in iron accumulation. The diferric transferrin molecule, when it did give up iron within the cell, released both of its iron atoms so that only apotransferrin was returned to the media. In contrast to the nearly complete release of iron within the normal reticulocyte, the major portion of iron taken up by the Belgrade reticulocyte was returned to the plasma. The release mechanism that can be impaired in iron-deficient reticulocytes by EDTA or cadmium was shown to be affected by lower concentrations of these substances in the Belgrade reticulocyte. It is concluded that the Belgrade rat has an abnormality of iron release within the absorptive vacuole that is responsible for a state of intracellular iron deficiency, involving the erythron and other body tissues.

scholarly journals Iron-Response Element Binding to Iron Regulatory Protein (IRP) 1 and 2 Are Indispensable for Adipose Tissue Browning

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1283-1283
Author(s):  
Mikyoung You ◽  
Soonkyu Chung
Keyword(s):  
Adipose Tissue ◽  
Iron Metabolism ◽  
Knockout Mice ◽  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Mrna Translation ◽  
Intracellular Iron ◽  
Mobility Shift ◽  
Iron Regulatory Proteins ◽  
Tissue Browning

Abstract Objectives Intracellular iron homeostasis is tightly regulated in posttranscriptional levels via iron regulatory proteins (IRPs). IRPs bind to the iron-responsive elements (IREs), leading to either mRNA translation or stability. Our recent study demonstrated that iron metabolism is intimately linked with adipose tissue browning and thermogenic activation. However, the role of IRP/IRE interactions in the adipose tissue is poorly understood. We aim to characterize the IRP/IRE interactions in the adipose tissue in terms of depot-specificity and thermogenic potential. Methods To induce adipocyte browning, mice were administrated with beta-3 adrenoceptor agonist CL316243 (CL) for 5 days, and different depots of adipose tissue of epididymal (eWAT), inguinal (iWAT), brown (BAT), and liver were collected. Iron metabolism and thermogenesis were evaluated. To investigate the IRP/IRE binding, electrophoretic mobility shift assay (EMSA) was performed in the cytosolic using the fluorescence-labeled IRE (IR-IRE). To distinguish the IRE binding with IRP1 and 2, the cytosolic fraction from IRP1 and 2 knockout mice were used as positive controls. Results In a normal temperature, the constitutive IRP/IRE binding was found in the BAT, but not in the eWAT and iWAT. In response to CL treatment, iron content and transferrin receptor levels significantly increased in the WAT. Accordingly, the IRE/IRPs binding significantly increased in the CL-treated iWAT. Genetic deletion of IRP1 or 2 poses a marginal impact on constitutively active BAT development, suggesting IRP1 and 2 plays a compensatory role. Unlikely to BAT, the deletion of either IRP1 or 2 failed to induce WAT browning in the IRP1 and 2 knockout mice with CL stimulation. Consistently, both IRE binding to IRP1 and 2 were manifest in the CL treated iWAT, implicating that IRP1 and 2 plays a separate and synergistic function for WAT browning. Conclusions Our study defined the depot-specific iron regulatory metabolism in the adipose tissue using an innovative EMSA method. We demonstrated that, for the first time in our knowledge, IRE binding to both IRP1 and IRP2 is indispensable for the thermogenic activation of WAT, which is distinct from the iron regulatory mechanism found in the BAT. We propose that iron metabolism in the WAT is a novel determinant for WAT browning and thermogenic energy expenditure. Funding Sources None.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Dan Chen ◽  
Anumantha G. Kanthasamy ◽  
Manju B. Reddy
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Regulatory Gene ◽  
Cell Uptake ◽  
Dopamine Depletion ◽  
Intracellular Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Sytox Green ◽  
Gene And Protein Expression

Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression.Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells.Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry.Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05) increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased55Fe (by 96%,p<0.01) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001) TH+cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons.Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.

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