scholarly journals Role of the iron‐import protein DMT1 (Divalent Metal Transporter 1) in liver iron uptake

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Chia-Yu Wang ◽  
Mitchell Knutson
Keyword(s):  
Iron Uptake ◽  
Divalent Metal ◽  
Liver Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter

scholarly journals The Divalent Metal Transporter 1 (DMT1) Is Required for Iron Uptake and Normal Development of Oligodendrocyte Progenitor Cells

2018 ◽  
Vol 38 (43) ◽  
pp. 9142-9159 ◽  
Author(s):  
Veronica T. Cheli ◽  
Diara A. Santiago González ◽  
Leandro N. Marziali ◽  
Norma N. Zamora ◽  
María E. Guitart ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Iron Uptake ◽  
Normal Development ◽  
Divalent Metal ◽  
Oligodendrocyte Progenitor Cells ◽  
Divalent Metal Transporter 1 ◽  
Oligodendrocyte Progenitor ◽  
Divalent Metal Transporter ◽  
Metal Transporter

scholarly journals The molecular basis of copper and iron interactions

2004 ◽  
Vol 63 (4) ◽  
pp. 563-569 ◽  
Author(s):  
Paul Sharp
Keyword(s):  
Apical Membrane ◽  
Dietary Supplementation ◽  
Intimate Relationship ◽  
Divalent Metal ◽  
Efflux Transporter ◽  
Transport Pathway ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter

The intimate relationship between Fe and Cu in human nutrition has been recognised for many years. The best-characterised link is provided by caeruloplasmin, a multiCu-binding protein that acts as a serum ferrioxidase and is essential for the mobilisation of Fe from storage tissues. Decreased Cu status has been shown to reduce holo-caeruloplasmin production and impair ferrioxidase activity, leading, in a number of cases, to decreased tissue Fe release and the generation of anaemia that is responsive to dietary supplementation with Cu but not Fe. Dietary Fe absorption also requires the presence of a multiCu ferrioxidase. Hephaestin, a caeruloplasmin homologue, works in concert with the IREG1 transporter to permit Fe efflux from enterocytes for loading onto transferrin. The essential role of hephaestin in this process has been recognised from studies in the sex-linked anaemic (sla) mouse, in which Fe efflux is markedly impaired as a result of a mutation in the hephaestin gene that results in a truncated and non-functional version of the protein. There is emerging evidence that a number of other components of the intestinal Fe transport pathway are also Cu sensitive. Divalent metal transporter 1 (DMT1), the Fe transporter located at the apical membrane of enterocytes, is also a physiologically-relevant Cu transporter, suggesting that these two metals may compete with each other for uptake into the duodenal enterocytes. Furthermore, expression of both DMT1 and the basolateral Fe-efflux transporter IREG1 can be regulated by Cu, suggesting that the Fe–Cu relationship may be more complex than first thought.

scholarly journals Small molecule inhibitors of divalent metal transporter-1

2009 ◽  
Vol 296 (4) ◽  
pp. G798-G804 ◽  
Author(s):  
Peter D. Buckett ◽  
Marianne Wessling-Resnick
Keyword(s):  
Small Molecule ◽  
Iron Metabolism ◽  
Iron Uptake ◽  
Small Molecule Inhibitors ◽  
Structural Features ◽  
Divalent Metal ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Copper Chelation ◽  
Metal Transporter

Divalent metal transporter-1 (DMT1) is a divalent cation transporter that plays a key role in iron metabolism by mediating ferrous iron uptake across the small intestine. We have previously identified several small molecule inhibitors of iron uptake ( 4 ). Using a cell line that stably overexpresses DMT1, we screened the ability of these inhibitors to specifically block this transporter's activity. One compound, NSC306711, inhibited DMT1-mediated iron uptake in a reversible and competitive manner. This inhibitor is a polysulfonated dye containing two copper centers. Although one of these two sites could be chelated by Triethylenetetramine copper chelation did not perturb NSC306711 inhibition of DMT1 activity. Several other polysulfonated dyes with structural features similar to NSC306711 were identified as potential DMT1 transport inhibitors. This study characterizes important pharmacological tools that can be used to probe DMT1's mechanism of iron transport and its role in iron metabolism.

Cytokine-mediated regulation of iron transport in human monocytic cells

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 4148-4154 ◽  
Author(s):  
Susanne Ludwiczek ◽  
Elmar Aigner ◽  
Igor Theurl ◽  
Günter Weiss
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Divalent Metal ◽  
Mrna Levels ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Regulatory Pathways ◽  
Metal Transporter ◽  
Cellular Expression ◽  
Ifn Γ

Abstract Under chronic inflammatory conditions cytokines induce a diversion of iron traffic, leading to hypoferremia and retention of the metal within the reticuloendothelial system. However, the regulatory pathways underlying these disturbances of iron homeostasis are poorly understood. We investigated transferrin receptor (TfR)–dependent and –independent iron transport mechanisms in cytokine-stimulated human monocytic cell lines THP-1 and U937. Combined treatment of cells with interferon-γ (IFN-γ) and lipopolysaccharide (LPS) reduced TfR mRNA levels, surface expression, and iron uptake, and these effects were reversed by interleukin-10 (IL-10), thus stimulating TfR-mediated iron acquisition. IFN-γ and LPS dose-dependently increased the cellular expression of divalent metal transporter-1, a transmembrane transporter of ferrous iron, and stimulated the uptake of nontransferrin bound iron (NTBI) into cells. At the same time, IFN-γ and LPS down-regulated the expression of ferroportin mRNA, a putative iron exporter, and decreased iron release from monocytes. Preincubation with IL-10 partly counteracted these effects. Our results demonstrate that the proinflammatory stimuli IFN-γ and LPS increase the uptake of NTBI via stimulation of divalent metal transporter-1 expression and cause retention of the metal within monocytes by down-regulating ferroportin synthesis. Opposite, the anti-inflammatory cytokine IL-10 stimulates TfR-mediated iron uptake into activated monocytes. The regulation of iron transport by cytokines is a key mechanism in the pathogenesis of anemia of chronic disease and a promising target for therapeutic intervention.

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