Expression of iron transport protein Divalent metal transporter 1 (DMT1) increases in response to maternal iron deficiency anemia in near term to term placenta

2020 ◽  
pp. 1-9
Author(s):  
Mullapudi Venkata Surekha ◽  
Thathapudi Sujatha ◽  
Shravanthi Gadhiraju ◽  
Putcha Uday Kumar ◽  
Mudili Siva Prasad ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Transport ◽  
Divalent Metal ◽  
Deficiency Anemia ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Near Term ◽  
Maternal Iron

scholarly journals Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Efrat Broide ◽  
Ram Reifen ◽  
Shay Matalon ◽  
Zipi Berkovich ◽  
Haim Shirin
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Transport ◽  
Deficiency Anemia ◽  
Diabetic Patients ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Transporter Proteins ◽  
Group A ◽  
Group B

The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72–1.46), 0.76 (0.53–1.04), and 0.71 (0.64–0.86), respectively (p=0.011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26–0.61), 0.36 (0.24–0.43), and 0.18 (0.16–0.24), respectively, (p=0.004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload

2001 ◽  
Vol 120 (6) ◽  
pp. 1412-1419 ◽  
Author(s):  
Heinz Zoller ◽  
Günter Weiss ◽  
Igor Theurl ◽  
Robert O. Koch ◽  
Wolfgang Vogel ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Divalent Metal ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Ferroportin 1

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.

The transcytosis of divalent metal transporter 1 and apo-transferrin during iron uptake in intestinal epithelium

2002 ◽  
Vol 283 (4) ◽  
pp. G965-G974 ◽  
Author(s):  
Yuxiang Ma ◽  
Robert D. Specian ◽  
Kwo-Yih Yeh ◽  
Mary Yeh ◽  
Juan Rodriguez-Paris ◽  
...  
Keyword(s):  
Iron Transport ◽  
Brush Border Membrane ◽  
Divalent Metal ◽  
Apical Surface ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Intestinal Epithelia ◽  
Metal Transporter ◽  
Apical Chamber ◽  
Texas Red

Caco-2 cells grown in bicameral chambers are a model system to study intestinal iron absorption. Caco-2 cells exhibit constitutive transport of iron from the apical (luminal) chamber to the basal (serosal) chamber that is enhanced by apo-transferrin in the basal chamber, with the apo-transferrin undergoing endocytosis to the apical portion of the cell. With the addition of iron to the apical surface, divalent metal transporter 1 (DMT1) on the brush-border membrane (BBM) undergoes endocytosis. These findings suggest that in Caco-2 cells DMT1 and apo-transferrin may cooperate in iron transport through transcytosis. To prove this hypothesis, we determined by confocal microscopy that, after addition of iron to the apical chamber, DMT1 from the BBM and Texas red apo-transferrin from the basal chamber colocalized in a perinuclear compartment. Colocalization was also observed by isolating endosomes from Caco-2 cells after ingestion of ultra-small paramagnetic particles from either the basal or apical chamber. The isolated endosomes contained both transferrin and DMT1 independent of the chamber from which the paramagnetic particles were endocytosed. These findings suggest that iron transport across intestinal epithelia may be mediated by transcytosis.

Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro

2001 ◽  
Vol 356 (3) ◽  
pp. 883-889 ◽  
Author(s):  
Lorraine GAMBLING ◽  
Ruth DANZEISEN ◽  
Susan GAIR ◽  
Richard G. LEA ◽  
Zehane CHARANIA ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Transferrin Receptor ◽  
Iron Transport ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Iron Transfer ◽  
Metal Transporter ◽  
Protein Levels ◽  
Copper Oxidase ◽  
Maternal Iron

Maternal iron deficiency during pregnancy induces anaemia in the developing fetus; however, the severity tends to be less than in the mother. The mechanism underlying this resistance has not been determined. We have measured placental expression of proteins involved in iron transfer in pregnant rats given diets with decreasing levels of iron and examined the effect of iron deficiency on iron transfer across BeWo cell layers, a model for placental iron transfer. Transferrin receptor expression was increased at both mRNA and protein levels. Similarly, expression of the iron-responsive element (IRE)-regulated form of the divalent metal transporter 1 (DMT1) was also increased. In contrast, the non-IRE regulated isoform showed no change in mRNA levels. Protein levels of DMT1 increased significantly. Iron efflux is thought to be mediated by the metal transporter protein, IREG1/ferroportin1/MTP1, and oxidation of Fe(II) to Fe(III) prior to incorporation into fetal transferrin is carried out by the placental copper oxidase. Expression of IREG1 was not altered by iron deficiency, whereas copper oxidase activity was increased. In BeWo cells made iron deficient by treatment with desferrioxamine (‘deferioxamine’), iron accumulation from iron-transferrin increased, in parallel with increased expression of the transferrin receptor. At the same time, iron efflux also increased, showing a higher flux of iron from the apical to the basolateral side. The data show that expression of placental proteins of iron transport are up-regulated in maternal iron deficiency, resulting in an increased efficiency of iron flux and a consequent minimization of the severity of fetal anaemia.

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