scholarly journals Iron Transporter Protein Expressions in Children with Celiac Disease

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 776
Author(s):  
Marleena Repo ◽  
Markus Hannula ◽  
Juha Taavela ◽  
Jari Hyttinen ◽  
Jorma Isola ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Iron Status ◽  
Negative Control ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Transporter Protein ◽  
Transferrin Receptor 1 ◽  
Protein Expressions ◽  
Duodenal Biopsies

Anemia is a frequent finding in children with celiac disease but the detailed pathophysiological mechanisms in the intestine remain obscure. One possible explanation could be an abnormal expression of duodenal iron transport proteins. However, the results have so far been inconsistent. We investigated this issue by comparing immunohistochemical stainings of duodenal cytochrome B (DCYTB), divalent metal transporter 1 (DMT1), ferroportin, hephaestin and transferrin receptor 1 (TfR1) in duodenal biopsies between 27 children with celiac disease and duodenal atrophy, 10 celiac autoantibody-positive children with potential celiac disease and six autoantibody-negative control children. Twenty out of these 43 subjects had anemia. The expressions of the iron proteins were investigated with regard to saturation and the percentage of the stained area or stained membrane length of the enterocytes. The results showed the stained area of ferroportin to be increased and the saturation of hephaestin to be decreased in celiac disease patients compared with controls. There were no differences in the transporter protein expressions between anemic and non-anemic patients. The present results suggest an iron status-independent alteration of ferroportin and hephaestin proteins in children with histologically confirmed celiac disease.

scholarly journals Impaired renal function and development in Belgrade rats

2014 ◽  
Vol 306 (3) ◽  
pp. F333-F343 ◽  
Author(s):  
Tania Veuthey ◽  
Dana Hoffmann ◽  
Vishal S. Vaidya ◽  
Marianne Wessling-Resnick
Keyword(s):  
Iron Status ◽  
Rat Kidney ◽  
Kidney Injury ◽  
Renal Physiology ◽  
Renal Metabolism ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Morphological Studies ◽  
Kidney Injury Molecule 1

Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ∼50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein.

scholarly journals Influence of DMT1 and iron status on inflammatory responses in the lung

2011 ◽  
Vol 300 (4) ◽  
pp. L659-L665 ◽  
Author(s):  
Jonghan Kim ◽  
Ramon M. Molina ◽  
Thomas C. Donaghey ◽  
Peter D. Buckett ◽  
Joseph D. Brain ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inflammatory Responses ◽  
Iron Status ◽  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Cell Content ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter

Divalent metal transporter 1 (DMT1) is the major iron transporter responsible for duodenal dietary iron absorption and is required for erythropoiesis. Recent studies suggest that loss of DMT1 activity could be involved in metal-related lung injury, but little is known about the effects of iron status and DMT1 function on pulmonary inflammation. To better define the role of DMT1 and iron status in pulmonary inflammatory responses, we performed bronchoalveolar lavage (BAL) following intratracheal instillation of lipopolysaccharide (LPS) to the Belgrade rat, an animal model deficient in DMT1 function. In the basal state, the BAL fluid of Belgrade rats had more macrophages and higher lactate dehydrogenase, myeloperoxidase, albumin, and hemoglobin levels compared with heterozygote control rats. Following LPS instillation, the macrophage fraction relative to total BAL cell content and levels of albumin and IgM were increased in Belgrade rats compared with controls. In contrast, heterozygote Belgrade rats made anemic by diet-induced iron deficiency exhibited attenuated inflammatory responses to LPS. These combined results show that pulmonary inflammation can be modified by both DMT1 and iron status. Loss of DMT1 alters pulmonary responses necessary for lung homeostasis in the basal state and enhances LPS-induced inflammation and therefore would contribute to progression of lung injury.

scholarly journals On Iron Metabolism and Its Regulation

2021 ◽  
Vol 22 (9) ◽  
pp. 4591
Author(s):  
Anne-Cathrine S. Vogt ◽  
Tasneem Arsiwala ◽  
Mona Mohsen ◽  
Monique Vogel ◽  
Vania Manolova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Peptide Hormone ◽  
Iron Regulation ◽  
Biological Processes ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Critical Metal ◽  
Transferrin Receptor 1

Iron is a critical metal for several vital biological processes. Most of the body’s iron is bound to hemoglobin in erythrocytes. Iron from senescent red blood cells is recycled by macrophages in the spleen, liver and bone marrow. Dietary iron is taken up by the divalent metal transporter 1 (DMT1) in enterocytes and transported to portal blood via ferroportin (FPN), where it is bound to transferrin and taken up by hepatocytes, macrophages and bone marrow cells via transferrin receptor 1 (TfR1). While most of the physiologically active iron is bound hemoglobin, the major storage of most iron occurs in the liver in a ferritin-bound fashion. In response to an increased iron load, hepatocytes secrete the peptide hormone hepcidin, which binds to and induces internalization and degradation of the iron transporter FPN, thus controlling the amount of iron released from the cells into the blood. This review summarizes the key mechanisms and players involved in cellular and systemic iron regulation.

Divalent metal transporter 1 (DMT1) and transferrin receptor (TfR) expression in duodenal biopsies from celiac patients

2001 ◽  
Vol 120 (5) ◽  
pp. A681
Author(s):  
Donatella Barisani ◽  
Antonina Parafioriti ◽  
Elisabetta Armiraglio ◽  
Dario Conte ◽  
Robert O. Koch ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Divalent Metal ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Duodenal Biopsies

scholarly journals Regulation of the Profile of Iron-Management Proteins in Brain Microvasculature

2004 ◽  
Vol 24 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Joseph R. Burdo ◽  
Ian A. Simpson ◽  
Sharon Menzies ◽  
John Beard ◽  
James R. Connor
Keyword(s):  
Iron Transport ◽  
Iron Status ◽  
Protein Profile ◽  
Brain Iron ◽  
Divalent Metal Transporter 1 ◽  
Iron Storage ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Brain Microvasculature ◽  
The Brain

The distribution of brain iron is heterogeneous, but the mechanism by which these regional differences are achieved and maintained is unknown. In this study, the authors test two hypotheses related to brain iron transport. The first is that there is regional variability in the profile of proteins associated with iron transport and storage in the brain microvasculature. The second hypothesis is that the iron status of the brain will dictate the response of the protein profile in the microvasculature to changes in systemic iron status. The profile analysis consists of transferrin (iron transport), ferritin (iron storage), transferrin receptor (iron uptake), and divalent metal transporter 1 (release of iron from endosomes). An additional protein involved in cellular iron efflux, ferroportin, was not detected in brain microvasculature. The results show that there are significantly higher levels of these proteins in the microvasculature from each area of the brain compared to a whole brain homogenate, but no regional differences within the microvasculature. The levels of ferritin observed in the microvasculature indicate that the microvascular endothelial cells have significant iron storage capacity. There are no significant changes in the regional protein profiles in response to systemic iron manipulation when brain iron status was normal. In contrast, in Belgrade rats, whose brain is iron deficient, the expression of both divalent metal transporter 1 and transferrin receptor was increased compared with control in almost all brain regions examined, but not transferrin or ferritin. These findings indicate that regional brain iron heterogeneity is not maintained by differences in microvascular iron-management protein levels. The results also indicate that brain iron status dictates the response of the microvascular protein profile to systemic iron manipulation.

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
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