scholarly journals CALCIUM AND IRON ABSORPTION: INVITRO STUDIES

2019 ◽  
Vol 3 (12) ◽  
Author(s):  
Bharat Kwatra
Keyword(s):  
Metal Uptake ◽  
Human Subjects ◽  
Basolateral Membrane ◽  
Dairy Farm ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Metal Retention ◽  
Cellular Metal ◽  
Short Period

Studies on human subjects have shown that Ca (Ca) will inhibit iron (Fe) absorption, regardless of whether or not it's given as Ca salts or in dairy farm products. This has caused concern as increased Ca intake usually is usually recommended for kids and girls, similar populations that are in danger of metal deficiency. However, a radical review of studies on humans during which Ca intake was considerably increased for long periods shows no changes in hematologic measures or indicators of iron standing. Thus, the repressing impact additionally be|is also} of short period and there also is also counteractive mechanisms. The interaction between Ca and metal is also a lumenal event, poignant metal uptake through DMT1 (divalent metal transporter 1) at the top membrane. However, it's additionally attainable that inhibition happens throughout metal transfer into circulation, suggesting roles for the serosal bourgeois ferroportin (FPN) and hephaestin. We explored these prospects in human enteral Caco-2 cells cultivated in monolayers. Iron transport (fifty nine Fe) and expression of DMT1, FPN, and hephaestin were assessed when one.5 and four hours with zero or a hundred μM CaCl 2. though Ca failed to have an effect on metal uptake or DMT1 expression at one.5 hours, FPN abundance at the basolateral membrane remittent, leading to increased cellular metal retention and remittent metal efflux. when four hours, DMT1 and FPN expression increased and there was an increased FPN.

Calcium and Iron Absorption - Mechanisms and Public Health Relevance

2010 ◽  
Vol 80 (45) ◽  
pp. 293-299 ◽  
Author(s):  
Bo Lönnerdal
Keyword(s):  
Short Duration ◽  
Human Subjects ◽  
Iron Status ◽  
Basolateral Membrane ◽  
Rebound Effect ◽  
Inhibitory Effect ◽  
Compensatory Mechanisms ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Fe Uptake

Studies on human subjects have shown that calcium (Ca) can inhibit iron (Fe) absorption, regardless of whether it is given as Ca salts or in dairy products. This has caused concern as increased Ca intake commonly is recommended for children and women, the same populations that are at risk of Fe deficiency. However, a thorough review of studies on humans in which Ca intake was substantially increased for long periods shows no changes in hematological measures or indicators of iron status. Thus, the inhibitory effect may be of short duration and there also may be compensatory mechanisms. The interaction between Ca and Fe may be a lumenal event, affecting Fe uptake through DMT1 (divalent metal transporter 1) at the apical membrane. However, it is also possible that inhibition occurs during Fe transfer into circulation, suggesting roles for the serosal exporter ferroportin (FPN) and hephaestin. We explored these possibilities in human intestinal Caco-2 cells cultured in monolayers. Iron transport (59Fe) and expression of DMT1, FPN, and hephaestin were assessed after 1.5 and 4 hours with 0 or 100 µM CaCl2. Although Ca did not affect Fe uptake or DMT1 expression at 1.5 hours, FPN abundance at the basolateral membrane decreased, resulting in increased cellular Fe retention and decreased Fe efflux. After 4 hours, DMT1 and FPN expression increased and there was increased FPN at the membrane, suggesting a rebound effect. Thus, the effect of Ca on Fe absorption may be of short duration and adaptation may occur with time. This may explain why studies on long-term Ca supplementation of different groups fail to show any adverse effects on Fe status.

scholarly journals Hepcidin inhibits apical iron uptake in intestinal cells

2008 ◽  
Vol 294 (1) ◽  
pp. G192-G198 ◽  
Author(s):  
Natalia P. Mena ◽  
Andrés Esparza ◽  
Victoria Tapia ◽  
Pamela Valdés ◽  
Marco T. Núñez
Keyword(s):  
Iron Uptake ◽  
Basolateral Membrane ◽  
Intestinal Cells ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Cell Monolayers ◽  
Metal Transporter ◽  
Protein Levels ◽  
J774 Cells ◽  
Iron Export

Hepcidin (Hepc) is considered a key mediator in iron trafficking. Although the mechanism of Hepc action in macrophages is fairly well established, much less is known about its action in intestinal cells, one of the main targets of Hepc. The current study investigated the effects of physiologically generated Hepc on iron transport in Caco-2 cell monolayers and rat duodenal segments compared with the effects on the J774 macrophage cell line. Addition of Hepc to Caco-2 cells or rat duodenal segments strongly inhibited apical 55Fe uptake without apparent effects on the transfer of 55Fe from the cells to the basolateral medium. Concurrently, the levels of divalent metal transporter 1 (DMT1) mRNA and protein in Caco-2 cells decreased while the mRNA and protein levels of the iron export transporter ferroportin did not change. Plasma membrane localization of ferroportin was studied by selective biotinylation of apical and basolateral membrane domains; Hepc induced rapid internalization of ferroportin in J774 cells but not in Caco-2 cells These results indicate that the effect of Hepc is cell dependent: in macrophages it inhibits iron export by inducing ferroportin degradation, whereas in enterocytes it inhibits apical iron uptake by inhibiting DMT1 transcription. Our results highlight the crucial role of Hepc in the control of intestinal iron absorption.

Iron Imports. V. Transport of iron through the intestinal epithelium

2006 ◽  
Vol 290 (3) ◽  
pp. G417-G422 ◽  
Author(s):  
Yuxiang Ma ◽  
Mary Yeh ◽  
Kwo-yih Yeh ◽  
Jonathan Glass
Keyword(s):  
Iron Transport ◽  
Brush Border Membrane ◽  
Iron Absorption ◽  
Basolateral Membrane ◽  
Apical Surface ◽  
Intracellular Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Apical Compartment

Iron absorption across the brush-border membrane requires divalent metal transporter 1 (DMT1), whereas ferroportin (FPN) and hephaestin are required for exit across the basolateral membrane. However, how iron passes across the enterocyte is poorly understood. Both chaperones and transcytosis have been postulated to account for intracellular iron transport. With iron feeding, DMT1 undergoes endocytosis and FPN translocates from the apical cytosol to the basolateral membrane. The fluorescent metallosensor calcein offered to the basolateral surface of enterocytes is found in endosomes in the apical compartment, and its fluorescence is quenched when iron is offered to the apical surface. These experiments are consistent with vesicular iron transport as a possible pathway for intracellular iron transport.

scholarly journals Iron deficiency during pregnancy: the consequences for placental function and fetal outcome

2013 ◽  
Vol 73 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Harry J. McArdle ◽  
Lorraine Gambling ◽  
Christine Kennedy
Keyword(s):  
Iron Deficiency ◽  
Basolateral Membrane ◽  
Fetal Outcome ◽  
Divalent Metal Transporter 1 ◽  
Altered Expression ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Expression Of Genes ◽  
Fetal Physiology ◽  
Short And Long Term

This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Trans-placental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up-regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short- and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies.

scholarly journals Iron Export through the Transporter Ferroportin 1 Is Modulated by the Iron Chaperone PCBP2

2016 ◽  
Vol 291 (33) ◽  
pp. 17303-17318 ◽  
Author(s):  
Izumi Yanatori ◽  
Des R. Richardson ◽  
Kiyoshi Imada ◽  
Fumio Kishi
Keyword(s):  
Mammalian Cells ◽  
Basolateral Membrane ◽  
Intracellular Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Cellular Iron ◽  
Ferroportin 1 ◽  
Iron Chaperone ◽  
Iron Export

Ferroportin 1 (FPN1) is an iron export protein found in mammals. FPN1 is important for the export of iron across the basolateral membrane of absorptive enterocytes and across the plasma membrane of macrophages. The expression of FPN1 is regulated by hepcidin, which binds to FPN1 and then induces its degradation. Previously, we demonstrated that divalent metal transporter 1 (DMT1) interacts with the intracellular iron chaperone protein poly(rC)-binding protein 2 (PCBP2). Subsequently, PCBP2 receives iron from DMT1 and then disengages from the transporter. In this study, we investigated the function of PCBP2 in iron export. Mammalian genomes encode four PCBPs (i.e. PCBP1–4). Here, for the first time, we demonstrated using both yeast and mammalian cells that PCBP2, but not PCBP1, PCBP3, or PCBP4, binds with FPN1. Importantly, iron-loaded, but not iron-depleted, PCBP2 interacts with FPN1. The PCBP2-binding domain of FPN1 was identified in its C-terminal cytoplasmic region. The silencing of PCBP2 expression suppressed FPN1-dependent iron export from cells. These results suggest that FPN1 exports iron received from the iron chaperone PCBP2. Therefore, it was found that PCBP2 modulates cellular iron export, which is an important physiological process.

scholarly journals Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

2021 ◽  
Vol 22 (15) ◽  
pp. 8013
Author(s):  
Taewook Kang ◽  
Honggang Huang ◽  
Thomas Mandrup-Poulsen ◽  
Martin R. Larsen
Keyword(s):  
Cell Death ◽  
Divalent Metal ◽  
Β Cells ◽  
Β Cell ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Knock Down ◽  
Metal Transporter ◽  
Cell Functions ◽  
Protective Proteins

Pro-inflammatory cytokines promote cellular iron-import through enhanced divalent metal transporter-1 (DMT1) expression in pancreatic β-cells, consequently cell death. Inhibition of β-cell iron-import by DMT1 silencing protects against apoptosis in animal models of diabetes. However, how alterations of signaling networks contribute to the protective action of DMT1 knock-down is unknown. Here, we performed phosphoproteomics using our sequential enrichment strategy of mRNA, protein, and phosphopeptides, which enabled us to explore the concurrent molecular events in the same set of wildtype and DMT1-silenced β-cells during IL-1β exposure. Our findings reveal new phosphosites in the IL-1β-induced proteins that are clearly reverted by DMT1 silencing towards their steady-state levels. We validated the levels of five novel phosphosites of the potential protective proteins using parallel reaction monitoring. We also confirmed the inactivation of autophagic flux that may be relevant for cell survival induced by DMT1 silencing during IL-1β exposure. Additionally, the potential protective proteins induced by DMT1 silencing were related to insulin secretion that may lead to improving β-cell functions upon exposure to IL-1β. This global profiling has shed light on the signal transduction pathways driving the protection against inflammation-induced cell death in β-cells after DMT1 silencing.

Does divalent metal transporter 1 mediate the intestinal absorption of arsenic?

2014 ◽  
Vol 229 ◽  
pp. S88
Author(s):  
Zeliha Kayaalti ◽  
Dilek Kaya Akyuzlu ◽  
Vugar Ali Türksoy ◽  
Esma Soylemez ◽  
Tulin Soylemezoglu
Keyword(s):  
Intestinal Absorption ◽  
Divalent Metal ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter

Copper repletion enhances apical iron uptake and transepithelial iron transport by Caco-2 cells

2002 ◽  
Vol 282 (3) ◽  
pp. G527-G533 ◽  
Author(s):  
Okhee Han ◽  
Marianne Wessling-Resnick
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Cell Monolayer ◽  
Transepithelial Transport ◽  
Apical Surface ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Copper Status ◽  
Copper Supplementation

The influence of copper status on Caco-2 cell apical iron uptake and transepithelial transport was examined. Cells grown for 7–8 days in media supplemented with 1 μM CuCl2had 10-fold higher cellular levels of copper compared with control. Copper supplementation did not affect the integrity of differentiated Caco-2 cell monolayers grown on microporous membranes. Copper-repleted cells displayed increased uptake of iron as well as increased transport of iron across the cell monolayer. Northern blot analysis revealed that expression of the apical iron transporter divalent metal transporter-1 (DMT1), the basolateral transporter ferroportin-1 (Fpn1), and the putative ferroxidase hephaestin (Heph) was upregulated by copper supplementation, whereas the recently identified ferrireductase duodenal cytochrome b (Dcytb) was not. These results suggest that DMT1, Fpn1, and Heph are involved in the iron uptake process modulated by copper status. Although a clear role for Dcytb was not identified, an apical surface ferrireductase was modulated by copper status, suggesting that its function also contributes to the enhanced iron uptake by copper-repleted cells. A model is proposed wherein copper promotes iron depletion of intestinal Caco-2 cells, creating a deficiency state that induces upregulation of iron transport factors.

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