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Journal articles on the topic 'DMT1'

Author: Grafiati

Published: 4 June 2021

Last updated: 27 April 2022

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1

Tabuchi, Mitsuaki, Naotaka Tanaka, Junko Nishida-Kitayama, Hiroshi Ohno, and Fumio Kishi. "Alternative Splicing Regulates the Subcellular Localization of Divalent Metal Transporter 1 Isoforms." Molecular Biology of the Cell 13, no. 12 (2002): 4371–87. http://dx.doi.org/10.1091/mbc.e02-03-0165.

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Divalent metal transporter 1 (DMT1) is responsible for dietary-iron absorption from apical plasma membrane in the duodenum and iron acquisition from the transferrin cycle endosomes in peripheral tissues. Two isoforms of the DMT1 transcript generated by alternative splicing of the 3′ exons have been identified in mouse, rat, and human. These isoforms can be distinguished by the different C-terminal amino acid sequences and by the presence (DMT1A) or absence (DMT1B) of an iron response element located in the 3′ untranslated region of the mRNA. However, it has been still unknown whether the struc

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2

Rolim, Luiz Clemente, João Roberto de Sá, Antonio Roberto Chacra, and Sérgio Atala Dib. "Heterogeneidade clínica e coexistência das neuropatias diabéticas: diferenças e semelhanças entre diabetes melito tipos 1 e 2." Arquivos Brasileiros de Endocrinologia & Metabologia 53, no. 7 (2009): 818–24. http://dx.doi.org/10.1590/s0004-27302009000700005.

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OBJETIVO: Estudar a heterogeneidade e a coexistência das neuropatias no diabetes melito tipos 1 (DMT1) e 2 (DMT2). MÉTODOS: Foram avaliados 74 DMT2 e 20 DMT1 em relação à idade (anos), tempo de diagnóstico do DM (TDDM, em anos), índice de massa corpórea (IMC, kg/m²), HbA1c e tipo de neuropatia (critérios da American Diabetes Association). RESULTADOS: DMT1 era mais jovem (32,7 ± 11 versus 56,9 ± 10,3; p = 0,0001), com maior TDDM (17,1 ± 9,7 versus 10,4 ± 6,8; p = 0,003) e menor IMC (23,6 ± 3,8 versus 28,4 ± 5,3; p = 0,0005). A neuropatia autonômica cardiovascular (NAC) (60% versus 32,4%; p = 0,

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3

Osorio-Concepción, Macario, Carlos Lax, Eusebio Navarro, Francisco E. Nicolás, and Victoriano Garre. "DNA Methylation on N6-Adenine Regulates the Hyphal Development during Dimorphism in the Early-Diverging Fungus Mucor lusitanicus." Journal of Fungi 7, no. 9 (2021): 738. http://dx.doi.org/10.3390/jof7090738.

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The epigenetic modifications control the pathogenicity of human pathogenic fungi, which have been poorly studied in Mucorales, causative agents of mucormycosis. This order belongs to a group referred to as early-diverging fungi that are characterized by high levels of N6-methyldeoxy adenine (6mA) in their genome with dense 6mA clusters associated with actively expressed genes. AlkB enzymes can act as demethylases of 6mA in DNA, with the most remarkable eukaryotic examples being mammalian ALKBH1 and Caenorhabditis elegans NMAD-1. The Mucor lusitanicus (formerly M. circinelloides f. lusitanicus)

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4

Ganeva, S., K. Todorova, Ts Lukanov, G. Rayanova, and S. Blajeva. "Levels of Lymphocyte Subpopulations in Peripheral Blood among Patients with Diabetes." Acta Medica Bulgarica 48, no. 1 (2021): 75–80. http://dx.doi.org/10.2478/amb-2021-0012.

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Abstract The aim of the study was to investigate the lymphocyte (lymph) subpopulations in peripheral blood as a part of the immune response among patients with diabetes mellitus type 1 (DMT1) and diabetes mellitus type 2 (DMT2). Patients and methods: A prospective, cross-sectional, comparative, “case-control” study was conducted among 22 patients with DMT1 and 70 patients with DMT2. The levels of lymph subtypes [general nonspecific T-lymph (CD3+); T-helper lymph (CD4+); T-cytotoxic lymph (CD8+), natural killers [NK cells (CD3\ CD16+/CD56)] and B-lymph (CD19+)] in blood was measured and compare

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5

Banks, Andrae, Lashawnda Fields, Curtis O’Dwyer, Marquisha Lawrence Scott, and Sean Joe. "Treating Mental Illness Among Diabetic Black Male Adolescents." Research on Social Work Practice 28, no. 3 (2017): 330–39. http://dx.doi.org/10.1177/1049731517702746.

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Objective: To examine randomized controlled trials (RCTs) for treatment evidence for Black male adolescents suffering from comorbid mental illness and diabetes mellitus. Method: A review of the studies published in English-language journals was conducted. Results: We found no RCT focused on Black males with diabetes mellitus Type 2 (DMT2). However, we found RCT inclusive of Black male adolescents with diabetes mellitus Type 1 (DMT1). Multisystemic therapy appears to be the best supported overall treatment for DMT1 management and psychosocial functioning followed by an enhanced form of behavior

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6

Cvetković, Tatjana, Predrag Vlahović, Vidosava đorđević, et al. "The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy." Journal of Medical Biochemistry 27, no. 3 (2008): 376–82. http://dx.doi.org/10.2478/v10011-008-0019-y.

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The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminu

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7

Hardianto, Dudi. "TELAAH KOMPREHENSIF DIABETES MELITUS: KLASIFIKASI, GEJALA, DIAGNOSIS, PENCEGAHAN, DAN PENGOBATAN." Jurnal Bioteknologi & Biosains Indonesia (JBBI) 7, no. 2 (2021): 304–17. http://dx.doi.org/10.29122/jbbi.v7i2.4209.

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Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. In general, diabetes is classified into type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational, and other specific diabetes. The causes of diabetes are genetic disorders and environmental. Common symptoms of diabetes include: polydipsia, polyphagia, glycosuria, polyuria, dehydration, fatigue, weight loss, reduced vision, cramps, constipation, and candida infection. Test for diagnosis of diabetes include: fasting plasma glucose test, plasma glucose test after 2 hours of 75 g oral glucose administrat

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8

Gunshin, Hiromi, Yuko Fujiwara, Angel O. Custodio, Cristina DiRenzo, Sylvie Robine, and Nancy C. Andrews. "Iron Metabolism in the Mice with Targeted Mutations of the DMT1 Gene ." Blood 104, no. 11 (2004): 50. http://dx.doi.org/10.1182/blood.v104.11.50.50.

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Abstract Divalent metal transporter 1 (DMT1) was shown to be important for iron metabolism through studies of the mk/mk mouse, which carries a spontaneous mutation (G185R) resulting in defective intestinal iron absorption and anemia. To further investigate the importance of this transporter in vivo, we inactivated the DMT1 gene through targeted deletion of transmembrane domains 3, 4 and 5. We obtained mice carrying a universally inactivated DMT1 allele (DMT1−/−) and mice carrying a floxed DMT1 allele that could be selectively inactivated by breeding to mice expressing a Cre recombinase transge

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9

Yeh, Kwo-Yih, Mary Yeh, J. Abra Watkins, Juan Rodriguez-Paris, and Jonathan Glass. "Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression." American Journal of Physiology-Gastrointestinal and Liver Physiology 279, no. 5 (2000): G1070—G1079. http://dx.doi.org/10.1152/ajpgi.2000.279.5.g1070.

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The divalent metal transporter (DMT1, also known as NRAMP2 or DCT1) is the likely target for regulation of intestinal iron absorption by iron stores. We investigated changes in intestinal DMT1 expression after a bolus of dietary iron in iron-deficient Belgrade rats homozygous for the DMT1 G185R mutation (b/b) and phenotypically normal heterozygous littermates (+/b). Immunofluorescent staining with anti-DMT1 antisera showed that DMT1 was located in the brush-border membrane. Duodenal DMT1 mRNA and protein levels were six- and twofold higher, respectively, in b/b rats than in +/b rats. At 1.5 h

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10

Okazaki, Yasumasa, Yuxiang Ma, Mary Yeh, et al. "DMT1 (IRE) expression in intestinal and erythroid cells is regulated by peripheral benzodiazepine receptor-associated protein 7." American Journal of Physiology-Gastrointestinal and Liver Physiology 302, no. 10 (2012): G1180—G1190. http://dx.doi.org/10.1152/ajpgi.00545.2010.

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The divalent metal transporter 1 (DMT1) is essential for cellular uptake of iron, mediating iron absorption across the duodenal brush border membrane. We have previously shown that with iron feeding DMT1 in the brush border membrane undergoes endocytosis into the subapical compartment of enterocytes. To understand the mechanisms of iron-induced endocytosis of DMT1, we used the yeast two-hybrid system to find proteins that interact with DMT1 and isolated from a rat duodenal cDNA library a protein that interacts specifically with the IRE containing isoform of DMT1 {DMT1 [iron-responsive element

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11

Soe-Lin, Shan, Sameer S. Apte, Marc R. Mikhael, Lidia Kayembe, Guangjun Nie, and Prem Ponka. "Both Nramp1 and Dmt1 Are Necessary for Efficient Macrophage Iron Recycling." Blood 114, no. 22 (2009): 1994. http://dx.doi.org/10.1182/blood.v114.22.1994.1994.

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Abstract Abstract 1994 Poster Board I-1016 Divalent metal transporter 1 (DMT1) and natural resistance-associated macrophage protein 1 (Nramp1) are iron transporters that localize, respectively, to the early and late endosomal compartments. DMT1 is ubiquitously expressed, while Nramp1 is found only within macrophages and neutrophils. Our previous studies have identified a role for Nramp1 during macrophage erythrophagocytosis; however, little is known about the function of DMT1 during this process. Wild-type RAW264.7 macrophages (Nramp1-/-), and those stably transfected with Nramp1 (Nramp1+/+) w

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12

Wareing, Mark, Carole J. Ferguson, Mathieu Delannoy, et al. "Altered dietary iron intake is a strong modulator of renal DMT1 expression." American Journal of Physiology-Renal Physiology 285, no. 6 (2003): F1050—F1059. http://dx.doi.org/10.1152/ajprenal.00064.2003.

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Divalent metal transporter1 (DMT1; also known as DCT1 or NRAMP2) is an important component of the cellular machinery responsible for dietary iron absorption in the duodenum. DMT1 is also highly expressed in the kidney where it has been suggested to play a role in urinary iron handling. In this study, we determined the effect on renal DMT1 expression of feeding an iron-restricted diet (50 mg/kg) or an iron-enriched diet (5 g/kg) for 4 wk and measured urinary and fecal iron excretion rates. Feeding the low-iron diet caused a reduction in serum iron concentration and fecal iron output rate with a

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13

Seo, Young Ah, Ruvin Kumara, Herbert Wetli, and Marianne Wessling-Resnick. "Regulation of divalent metal transporter-1 by serine phosphorylation." Biochemical Journal 473, no. 22 (2016): 4243–54. http://dx.doi.org/10.1042/bcj20160674.

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Divalent metal transporter-1 (DMT1) mediates dietary iron uptake across the intestinal mucosa and facilitates peripheral delivery of iron released by transferrin in the endosome. Here, we report that classical cannabinoids (Δ9-tetrahydrocannabinol, Δ9-THC), nonclassical cannabinoids (CP 55,940), aminoalkylindoles (WIN 55,212-2) and endocannabinoids (anandamide) reduce 55Fe and 54Mn uptake by HEK293T(DMT1) cells stably expressing the transporter. siRNA knockdown of cannabinoid receptor type 2 (CB2) abrogated inhibition. CB2 is a G-protein (GTP-binding protein)-coupled receptor that negatively r

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14

Griffin, Kathleen P., Donald T. Ward, Wei Liu, Gavin Stewart, Ian D. Morris, and Craig P. Smith. "Differential expression of divalent metal transporter DMT1 (Slc11a2) in the spermatogenic epithelium of the developing and adult rat testis." American Journal of Physiology-Cell Physiology 288, no. 1 (2005): C176—C184. http://dx.doi.org/10.1152/ajpcell.00061.2004.

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Iron is essential for male fertility, and disruptions in iron balance lead to impairment of testicular function. The divalent metal transporter DMT1 is a key modulator of transferrin- and non-transferrin-bound iron homeostasis. As a first step in determining the role of DMT1 in the testis, we have characterized the pattern of DMT1 expression in the developing and adult rat testis. Northern blot analysis and RT-PCR of testis polyadenylated RNA revealed the presence of iron-responsive element (IRE) and non-IRE transcripts. Semiquantitative immunoblotting of immature and adult rat testis uncovere

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15

Esparza, Andrés, Ziomara P. Gerdtzen, Alvaro Olivera-Nappa, J. Cristian Salgado, and Marco T. Núñez. "Iron-induced reactive oxygen species mediate transporter DMT1 endocytosis and iron uptake in intestinal epithelial cells." American Journal of Physiology-Cell Physiology 309, no. 8 (2015): C558—C567. http://dx.doi.org/10.1152/ajpcell.00412.2014.

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Recent evidence shows that iron induces the endocytosis of the iron transporter dimetal transporter 1 (DMT1) during intestinal absorption. We, and others, have proposed that iron-induced DMT1 internalization underlies the mucosal block phenomena, a regulatory response that downregulates intestinal iron uptake after a large oral dose of iron. In this work, we investigated the participation of reactive oxygen species (ROS) in the establishment of this response. By means of selective surface protein biotinylation of polarized Caco-2 cells, we determined the kinetics of DMT1 internalization from t

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16

Wibisono, Wahyu, and Harjoedi Adji Tjahjono. "Hubungan Kadar 25-Hidroksi-Vitamin D dengan HbA1c Melalui Interleukin-17 pada Anak Diabetes Melitus Tipe 1." Sari Pediatri 17, no. 6 (2016): 469. http://dx.doi.org/10.14238/sp17.6.2016.469-77.

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Latar belakang. Diabetes melitus tipe 1 (DMT1) merupakan penyakit autoimun yang ditandai oleh destruksi sel β pankreas danberhubungan dengan aktivitas Th17.Tujuan. Mengetahui hubungan antara kadar vitamin D dengan kadar HbA1c melalui IL-17 pada anak dengan DMT1.Metode. Desain cross-sectional dan melibatkan 20 subjek DM dan 20 kontrol sehat. Kadar vitamin D diukur dengan metode EIA (ng/mL), kadar HbA1c diukur dengan metode kromatografi menggunakan HPLC (%), IL-17 diukur dengan metode ELISA (pg/mL).Hasil. Kadar vitamin D pada kelompok DMT1 lebih rendah dibandingkan kelompok kontrol (p<0,05).

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17

Abouhamed, Marouan, Natascha A. Wolff, Wing-Kee Lee, Craig P. Smith, and Frank Thévenod. "Knockdown of endosomal/lysosomal divalent metal transporter 1 by RNA interference prevents cadmium-metallothionein-1 cytotoxicity in renal proximal tubule cells." American Journal of Physiology-Renal Physiology 293, no. 3 (2007): F705—F712. http://dx.doi.org/10.1152/ajprenal.00198.2007.

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Chronic exposure to Cd2+ causes renal proximal tubular (PT) damage. Cd2+ reaches the PT mainly as cadmium-metallothionein 1 (CdMT-1) complexes that are filtered at the glomerulus and then internalized in part via endocytosis mediated by megalin and cubulin. Subsequently, Cd2+ is thought to be released in the cytosol to activate cell death pathways. The proton-coupled divalent metal transporter DMT1 also transports Cd2+ and is expressed exclusively in endosomes/lysosomes in rat PT cells. Using vector-based RNA interference with short-hairpin small-interfering RNAs (shRNAs) to downregulate DMT1

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18

Canonne-Hergaux, François, An-Sheng Zhang, Prem Ponka, and Philippe Gros. "Characterization of the iron transporter DMT1 (NRAMP2/DCT1) in red blood cells of normal and anemic mk/mkmice." Blood 98, no. 13 (2001): 3823–30. http://dx.doi.org/10.1182/blood.v98.13.3823.

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Abstract Divalent metal transporter 1 (DMT1) is the major transferrin-independent iron uptake system at the apical pole of intestinal cells, but it may also transport iron across the membrane of acidified endosomes in peripheral tissues. Iron transport and expression of the 2 isoforms of DMT1 was studied in erythroid cells that consume large quantities of iron for biosynthesis of hemoglobin. In mk/mk mice that express a loss-of-function mutant variant of DMT1, reticulocytes have a decreased cellular iron uptake and iron incorporation into heme. Interestingly, iron release from transferrin insi

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Ilyechova, Ekaterina, Elisa Bonaldi, Iurii Orlov, Ekaterina Skomorokhova, Ludmila Puchkova, and Massimo Broggini. "CRISP-R/Cas9 Mediated Deletion of Copper Transport Genes CTR1 and DMT1 in NSCLC Cell Line H1299. Biological and Pharmacological Consequences." Cells 8, no. 4 (2019): 322. http://dx.doi.org/10.3390/cells8040322.

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Copper, the highly toxic micronutrient, plays two essential roles: it is a catalytic and structural cofactor for Cu-dependent enzymes, and it acts as a secondary messenger. In the cells, copper is imported by CTR1 (high-affinity copper transporter 1), a transmembrane high-affinity copper importer, and DMT1 (divalent metal transporter). In cytosol, enzyme-specific chaperones receive copper from CTR1 C-terminus and deliver it to their apoenzymes. DMT1 cannot be a donor of catalytic copper because it does not have a cytosol domain which is required for copper transfer to the Cu-chaperons that ass

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20

Yanatori, Izumi, Yumiko Yasui, Mitsuaki Tabuchi, and Fumio Kishi. "Chaperone protein involved in transmembrane transport of iron." Biochemical Journal 462, no. 1 (2014): 25–37. http://dx.doi.org/10.1042/bj20140225.

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Iron-associated DMT1 can interact with poly(rC)-binding protein 2 (PCBP2), although iron-chelated DMT1 cannot. PCBP2 can transfer Fe2+ from DMT1 to the appropriate sites or to ferroportin as an iron chaperone.

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21

Kondaiah, Palsa, Mohamad F. Aslam, Purna Chandra Mashurabad, Paul A. Sharp, and Raghu Pullakhandam. "Zinc induces iron uptake and DMT1 expression in Caco-2 cells via a PI3K/IRP2 dependent mechanism." Biochemical Journal 476, no. 11 (2019): 1573–83. http://dx.doi.org/10.1042/bcj20180939.

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Abstract The absorption of iron is influenced by numerous dietary and physiological factors. We have previously demonstrated that zinc treatment of intestinal cells increases iron absorption via induction of the apical membrane iron transporter divalent metal ion transporter-1 (DMT1). To better understand the mechanisms of zinc-induced iron absorption, we have studied the effect of zinc on iron uptake, iron transporter and iron regulatory protein (IRP 1 and 2) expression and the impact of the PI3K pathway in differentiated Caco-2 cells, an intestinal cell culture model. We found that zinc indu

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22

Montalbetti, Nicolas, Alexandre Simonin, Marianela G. Dalghi, Gergely Kovacs, and Matthias A. Hediger. "Development and Validation of a Fast and Homogeneous Cell-Based Fluorescence Screening Assay for Divalent Metal Transporter 1 (DMT1/SLC11A2) Using the FLIPR Tetra." Journal of Biomolecular Screening 19, no. 6 (2014): 900–908. http://dx.doi.org/10.1177/1087057114521663.

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Divalent metal ion transporter 1 (DMT1) is a proton-coupled Fe2+ transporter that is essential for iron uptake in enterocytes and for transferrin-associated endosomal iron transport in many other cell types. DMT1 dysfunction is associated with several diseases such as iron overload disorders and neurodegenerative diseases. The main objective of the present work is to develop and validate a fluorescence-based screening assay for DMT1 modulators. We found that Fe2+ or Cd2+ influx could be reliably monitored in calcium 5–loaded DMT1-expressing HEK293 cells using the FLIPR Tetra fluorescence micro

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23

Liang, Jiayan, Yan He, Qiuxin Zhang, Wenyi Wang, and Zemin Zhang. "Plasma Membrane Ca2+ Permeable Mechanosensitive Channel OsDMT1 Is Involved in Regulation of Plant Architecture and Ion Homeostasis in Rice." International Journal of Molecular Sciences 21, no. 3 (2020): 1097. http://dx.doi.org/10.3390/ijms21031097.

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Plant architecture is an important factor for crop production. Plant height, tiller pattern, and panicle morphology are decisive factors for high grain yield in rice. Here, we isolated and characterized a T-DNA insertion rice mutant Osdmt1 (Oryza sativa dwarf and multi-tillering1) that exhibited a severe dwarf phenotype and multi-tillering. Molecular cloning revealed that DMT1 encodes a plasma membrane protein that was identified as a putative Ca2+ permeable mechanosensitive channel. The transcript expression level was significantly higher in the dmt1 mutant compared to wild type (WT). Additio

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Olivi, Luisa, Jeanne Sisk, and Joseph Bressler. "Involvement of DMT1 in uptake of Cd in MDCK cells: role of protein kinase C." American Journal of Physiology-Cell Physiology 281, no. 3 (2001): C793—C800. http://dx.doi.org/10.1152/ajpcell.2001.281.3.c793.

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The involvement of iron (Fe) transporters in the uptake of cadmium (Cd) was examined in Madin-Darby kidney cells (MDCK). The uptake of Cd displayed properties that are associated with the Fe transporter divalent metal transporter 1 (DMT1). For example, the uptake of Cd and Fe was reduced by altering the cell membrane potential. The uptake of Cd was blocked by Fe, and the uptake of Fe was blocked by Cd. Also, the uptake of Cd and Fe was higher in MDCK cells bathed in a buffer at low pH. Increased uptake of Fe and Cd was observed in the HEK-293 cell line overexpressing DMT1. Overnight treatment

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Kang, Taewook, Honggang Huang, Thomas Mandrup-Poulsen та Martin R. Larsen. "Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery". International Journal of Molecular Sciences 22, № 15 (2021): 8013. http://dx.doi.org/10.3390/ijms22158013.

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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 D

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Worthington, Mark T., Lauren Browne, Emily H. Battle, and Roger Qi Luo. "Functional properties of transfected human DMT1 iron transporter." American Journal of Physiology-Gastrointestinal and Liver Physiology 279, no. 6 (2000): G1265—G1273. http://dx.doi.org/10.1152/ajpgi.2000.279.6.g1265.

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Recently, mutation of the DMT1 gene has been discovered to cause ineffective intestinal iron uptake and abnormal body iron metabolism in the anemic Belgrade rat and mkmouse. DMT1 transports first-series transition metals, but only iron turns on an inward proton current. The process of iron transport was studied by transfection of human DMT1 into the COS-7 cell line. Native and epitope-tagged human DMT1 led to increased iron uptake. The human gene with the Belgrade rat mutation was found to have one-fifth of the activity of the wild-type protein. The pH optimum of human DMT1 iron uptake was 6.7

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Mims, Martha P., Yongli Guan, and Josef T. Prchal. "DMT1: Tissue Specific Expression and Alternative Splicing." Blood 104, no. 11 (2004): 3210. http://dx.doi.org/10.1182/blood.v104.11.3210.3210.

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Abstract Divalent metal ion transporter 1 (DMT1) functions in iron absorption at the apical surface of the duodenal enterocyte and in iron transport out of the endosomal compartment of the erythroblast, however, DMT1 is also expressed in cells which have no apparent role in iron metabolism. At least 4 isoforms of DMT1 mRNA have been identified that contain alternative 5′ (1A, 1B) and 3′ (IRE+, IRE-) exons. Recently we reported the first human mutation of the DMT1 gene in a patient with severe hypochromic/microcytic anemia. This patient was homozygous for a mutation in the ultimate nucleotide o

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Mackenzie, Bryan, Hitomi Takanaga, Nadia Hubert, Andreas Rolfs, and Matthias A. Hediger. "Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1)." Biochemical Journal 403, no. 1 (2007): 59–69. http://dx.doi.org/10.1042/bj20061290.

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DMT1 (divalent metal-ion transporter 1) is a widely expressed metal-ion transporter that is vital for intestinal iron absorption and iron utilization by most cell types throughout the body, including erythroid precursors. Mutations in DMT1 cause severe microcytic anaemia in animal models. Four DMT1 isoforms that differ in their N- and C-termini arise from mRNA transcripts that vary both at their 5′-ends (starting in exon 1A or exon 1B) and at their 3′-ends giving rise to mRNAs containing (+) or lacking (−) the 3′-IRE (iron-responsive element) and resulting in altered C-terminal coding sequence

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Buckett, Peter D., and Marianne Wessling-Resnick. "Small molecule inhibitors of divalent metal transporter-1." American Journal of Physiology-Gastrointestinal and Liver Physiology 296, no. 4 (2009): G798—G804. http://dx.doi.org/10.1152/ajpgi.90342.2008.

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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 s

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Ghio, Andrew J., Xinchao Wang, Robert Silbajoris, Michael D. Garrick, Claude A. Piantadosi, and Funmei Yang. "DMT1 expression is increased in the lungs of hypotransferrinemic mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 284, no. 6 (2003): L938—L944. http://dx.doi.org/10.1152/ajplung.00225.2002.

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Despite a lack of transferrin, hypotransferrinemic (Hp) mice demonstrate an accumulation of iron in peripheral organs including the lungs. One potential candidate for such transferrin-independent uptake of iron is divalent metal transporter-1 (DMT1), an established iron transporter. We tested the hypothesis that increased concentrations of iron in the lungs of Hp mice are associated with elevations in DMT1 expression. With the use of inductively coupled plasma emission spectroscopy, measurements of nonheme iron confirmed significantly elevated concentrations in the lung tissue of Hp mice relat

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Wang, Xinchao, Michael D. Garrick, Funmei Yang, Lisa A. Dailey, Claude A. Piantadosi та Andrew J. Ghio. "TNF, IFN-γ, and endotoxin increase expression of DMT1 in bronchial epithelial cells". American Journal of Physiology-Lung Cellular and Molecular Physiology 289, № 1 (2005): L24—L33. http://dx.doi.org/10.1152/ajplung.00428.2003.

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Regulation of the metal transport protein divalent metal transporter-1 (DMT1) may contribute to the uptake and detoxification of iron by cells resident in the respiratory tract. Inflammation has been associated with an increased availability of this metal resulting in an oxidative stress. Because proinflammatory cytokines and LPS have been demonstrated to affect an elevated expression of DMT1 in a macrophage cell line, we tested the hypothesis that tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and LPS increase DMT1 expression in airway epithelial cells. We used RT-PCR to detect mRNA for b

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Arredondo, M., V. Cambiazo, L. Tapia, et al. "Copper overload affects copper and iron metabolism in Hep-G2 cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 287, no. 1 (2004): G27—G32. http://dx.doi.org/10.1152/ajpgi.00297.2003.

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Divalent metal transporter #1 (DMT1) is responsible for intestinal nonheme Fe apical uptake. However, DMT1 appears to have an additional function in Cu transport in intestinal cells. Because the liver has an essential role in body Cu homeostasis, we examined the potential involvement of Cu in the regulation of DMT1 expression and activity in Hep-G2 cells. Cells exposed to 10 μM Cu exhibited a 22-fold increase in Cu content and a twofold decrease in Fe content compared with cells maintained in 0.4 μM Cu. 64Cu uptake in Cu-deficient Hep-G2 cells showed a twofold decrease in Km compared with cell

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Wu, Dunli, Yi Soong, Guo-Min Zhao, and Hazel H. Szeto. "A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning." American Journal of Physiology-Heart and Circulatory Physiology 283, no. 2 (2002): H783—H791. http://dx.doi.org/10.1152/ajpheart.00193.2002.

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We recently discovered an opioid peptide analgesic, 2′,6′-dimethyltyrosine (Dmt)-d-Arg-Phe-Lys-NH2([Dmt1]DALDA), that can protect against ischemia-induced myocardial stunning. In buffer-perfused hearts, 30-min global ischemia followed by reperfusion resulted in a significant increase in norepinephrine (NE) overflow immediately upon reperfusion and significant decline in contractile force (45%). Pretreatment with [Dmt1]DALDA before ischemia completely abolished myocardial stunning and significantly reduced NE overflow (68%). In contrast, pretreatment with morphine before ischemia only provided

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Deja, Grazyna, Przemyslawa Jarosz-Chobot, Joanna Polanska, Urszula Siekiera та Ewa Malecka-Tendera. "Is the Association Between TNF-α-308 A Allele and DMT1 Independent of HLA-DRB1, DQB1 Alleles?" Mediators of Inflammation 2006 (2006): 1–7. http://dx.doi.org/10.1155/mi/2006/19724.

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The aim of the study was to assess chosen factors of genetic susceptibility to DMT1: DRB1, DQB1, and TNF-αpolymorphisms-308 (G/A) in children with DMT1 and their up-to-now healthy siblings. Then we tested whether the association between TNF-αgenes and DMT1 is independent of HLA. 87 diabetic children, their 78 siblings, and 85 persons from healthy control group were followed up. The highest risk of DMT1 was connected with alleles: DRB1*0401 (OR = 3.39; CI: 1.55–7.41), DRB1*0301 (OR = 2.72; CI: 1.48–5.01), DQB1*0201 (OR = 4.04; CI: 2.17–7.52), DQB1*0302 (OR = 5.08; CI: 2.54–10.14), and TNF-α-308

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Priwitzerova, Monika, Guangjun Nie, Alex D. Sheftel, Dagmar Pospisilova, Vladimir Divoky, and Prem Ponka. "Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake." Blood 106, no. 12 (2005): 3985–87. http://dx.doi.org/10.1182/blood-2005-04-1550.

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We have previously described a case of severe hypochromic microcytic anemia caused by a homozygous mutation in the divalent metal transporter 1 (DMT1 1285G > C). This mutation encodes for an amino acid substitution (E399D) and causes preferential skipping of exon 12 during processing of the DMT1 mRNA. To examine the functional consequences of this mutation, full-length DMT1 transcript with the patient's point mutation or a DMT1 transcript with exon 12 deleted was expressed in Chinese hamster ovary (CHO) cells. Our results demonstrate that the E399D substitution has no effect on protein expr

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Canonne-Hergaux, François, Joanne E. Levy, Mark D. Fleming, Lynne K. Montross, Nancy C. Andrews, and Philippe Gros. "Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders." Blood 97, no. 4 (2001): 1138–40. http://dx.doi.org/10.1182/blood.v97.4.1138.

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Abstract Iron overload is highly prevalent, but its molecular pathogenesis is poorly understood. Recently, DMT1 was shown to be a major apical iron transporter in absorptive cells of the duodenum. In vivo, it is the only transporter known to be important for the uptake of dietary non-heme iron from the gut lumen. The expression and subcellular localization of DMT1 protein in 3 mouse models of iron overload were examined: hypotransferrinemic (Trfhpx) mice, Hfeknockout mice, and B2m knockout mice. Interestingly, in Trfhpx homozygotes, DMT1 expression was strongly induced in the villus brush bord

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Abouhamed, Marouan, Jakub Gburek, Wei Liu, et al. "Divalent metal transporter 1 in the kidney proximal tubule is expressed in late endosomes/lysosomal membranes: implications for renal handling of protein-metal complexes." American Journal of Physiology-Renal Physiology 290, no. 6 (2006): F1525—F1533. http://dx.doi.org/10.1152/ajprenal.00359.2005.

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The H+-coupled polyligand transport protein divalent metal transporter 1 (DMT1) plays a key role in mammalian iron homeostasis. It has a widespread pattern of expression including tissues associated with iron acquisition and storage. Interestingly, it is also highly expressed in the kidney, yet its function in this tissue is unknown. The aim of this study was to determine the cellular location of DMT1 in proximal tubule cells as a first step to determining the role of this protein in the kidney. To do this we performed RT-PCR and immunostaining experiments using rat kidney and the S1 proximal

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Núñez, Marco T., Victoria Tapia, Alejandro Rojas, Pabla Aguirre, Francisco Gómez, and Francisco Nualart. "Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1." American Journal of Physiology-Cell Physiology 298, no. 3 (2010): C477—C485. http://dx.doi.org/10.1152/ajpcell.00168.2009.

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Intestinal iron absorption comprises the coordinated activity of the influx transporter divalent metal transporter 1 (DMT1) and the efflux transporter ferroportin (FPN). In this work, we studied the movement of DMT1 and FPN between cellular compartments as a function of iron supply. In rat duodenum, iron gavage resulted in the relocation of DMT1 to basal domains and the internalization of basolateral FPN. Considerable FPN was also found in apical domains. In Caco-2 cells, the apical-to-basal movement of cyan fluorescent protein-tagged DMT1 was complete 90 min after the addition of iron. Steady

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Zidova, Zuzana, Daniel Garcia-Santos, Katarina Kapralova, et al. "Oxidative Stress and Increased Destruction of Red Blood Cells Contribute to the Pathophysiology of Anemia Caused By DMT1 Deficiency." Blood 124, no. 21 (2014): 4027. http://dx.doi.org/10.1182/blood.v124.21.4027.4027.

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Abstract Inactivating mutations in divalent metal transporter 1 (DMT1) are associated with a severe defect in erythroid iron utilization and cause moderate to severe hypochromic microcytic anemia in human patients and two rodent models. We have previously shown that DMT1 deficiency impairs erythroid differentiation, induces apoptosis of erythroid precursors and causes the suppression of colony-forming capacity of erythroid progenitors. Using in vitro cultures of fetal liver cells we were able to recapitulate this in vivo defect. We confirmed abnormal pattern of erythroid differentiation and in

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Lopez, Veronica, Yasushi A. Suzuki, and Bo Lönnerdal. "Ontogenic changes in lactoferrin receptor and DMT1 in mouse small intestine: implications for iron absorption during early lifeThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process." Biochemistry and Cell Biology 84, no. 3 (2006): 337–44. http://dx.doi.org/10.1139/o06-059.

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It has been proposed that lactoferrin receptor (LfR) may be involved in intestinal iron transport during early life. However, it is known that iron homeostasis is regulated by divalent metal transporter 1 (DMT1; Nramp2/DCT1) in the adult small intestine. To address the hypothesis that LfR may play a role as an alternative iron transport pathway during early life, we used immunohistochemistry (IHC) to examine the localization of mouse LfR (mLfR) and DMT1. In addition to studying the localization and abundance of LfR and DMT1 on the apical membrane, intestinal brush-border membrane vesicles (BBM

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Kim, Jonghan, Ramon M. Molina, Thomas C. Donaghey, Peter D. Buckett, Joseph D. Brain, and Marianne Wessling-Resnick. "Influence of DMT1 and iron status on inflammatory responses in the lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 300, no. 4 (2011): L659—L665. http://dx.doi.org/10.1152/ajplung.00343.2010.

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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 func

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Shu, Rui-Chen, Lin-Lin Zhang, Chun-Yan Wang, et al. "Spinal Peroxynitrite Contributes to Remifentanil-induced Postoperative Hyperalgesia via Enhancement of Divalent Metal Transporter 1 without Iron-responsive Element–mediated Iron Accumulation in Rats." Anesthesiology 122, no. 4 (2015): 908–20. http://dx.doi.org/10.1097/aln.0000000000000562.

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Abstract Background: Hyperalgesia is one of the negative consequences following intraoperative analgesia with remifentanil. Peroxynitrite is a critical determinant in nociceptive process. Peroxynitrite inactivates iron-sulfur cluster that results in mitochondrial dysfunction and the release of iron, leading to mitochondrial iron accumulation. Iron accumulation mediated by divalent metal transporter 1 (DMT1) plays a key role in N-methyl-d-aspartate neurotoxicity. This study aims to determine whether peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via DMT1-mediated i

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Wang, Xiaoyu, Mingzhen Zhang, Regina R. Woloshun, et al. "Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice." Nutrients 13, no. 5 (2021): 1686. http://dx.doi.org/10.3390/nu13051686.

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Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically

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Oates, Phillip S., Carla Thomas, Elizabeth Freitas, Matthew J. Callow, and Evan H. Morgan. "Gene expression of divalent metal transporter 1 and transferrin receptor in duodenum of Belgrade rats." American Journal of Physiology-Gastrointestinal and Liver Physiology 278, no. 6 (2000): G930—G936. http://dx.doi.org/10.1152/ajpgi.2000.278.6.g930.

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Regulation of iron absorption is thought to be mediated by the amount of iron taken up by duodenal crypt cells via the transferrin receptor (TfR)-transferrin cycle and the activity of the divalent metal transporter (DMT1), although DMT1 cannot be detected morphologically in crypt cells. We investigated the uptake of transferrin-bound iron by duodenal enterocytes in Wistar rats fed different levels of iron and Belgrade (b/b) rats in which iron uptake by the transferrin cycle is defective because of a mutation in DMT1. We showed that DMT1 in our colony of b/b rats contains the G185R mutation, wh

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Jabado, Nada, François Canonne-Hergaux, Samantha Gruenheid, Virgine Picard, and Philippe Gros. "Iron transporter Nramp2/DMT-1 is associated with the membrane of phagosomes in macrophages and Sertoli cells." Blood 100, no. 7 (2002): 2617–22. http://dx.doi.org/10.1182/blood-2002-04-1182.

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Nramp2 (DMT1) is a pH-dependent divalent cation transporter that acts as the transferrin-independent iron uptake system at the intestinal brush border and also transports iron released from transferrin across the membrane of acidified endosomes. In this study, RAW264.7 macrophages and 2 independently derived murine Sertoli cells lines, TM4 and 15P-1, were used to further study the subcellular localization of Nramp2/DMT1 in phagocytic cells, including possible recruitment to the phagosomal membrane. Nramp2/DMT1 was localized primarily to the EEA1-positive recycling endosome compartment, with so

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Minor, Emily A., Justin T. Kupec, Andrew J. Nickerson, Karthikeyan Narayanan, and Vazhaikkurichi M. Rajendran. "Increased DMT1 and FPN1 expression with enhanced iron absorption in ulcerative colitis human colon." American Journal of Physiology-Cell Physiology 318, no. 2 (2020): C263—C271. http://dx.doi.org/10.1152/ajpcell.00128.2019.

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Iron deficiency anemia is a common complication of ulcerative colitis (UC) that can profoundly impact quality of life. Most iron absorption occurs in the duodenum via divalent metal transporter 1 (DMT1)-mediated uptake and ferroportin-1 (FPN1)-mediated export across the apical and basolateral membranes, respectively. However, the colon also contains iron transporters and can participate in iron absorption. Studies have shown increased duodenal DMT1 and FPN1 in patients with UC, but there is conflicting evidence about whether expression is altered in UC colon. We hypothesized that expression of

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Ghio, Andrew J., Claude A. Piantadosi, Xinchao Wang, et al. "Divalent metal transporter-1 decreases metal-related injury in the lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 289, no. 3 (2005): L460—L467. http://dx.doi.org/10.1152/ajplung.00154.2005.

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Exposure to airborne particulates makes the detoxification of metals a continuous challenge for the lungs. Based on the fate of iron in airway epithelial cells, we postulated that divalent metal transporter-1 (DMT1) participates in detoxification of metal associated with air pollution particles. Homozygous Belgrade rats, which are functionally deficient in DMT1, exhibited diminished metal transport from the lower respiratory tract and greater lung injury than control littermates when exposed to oil fly ash. Preexposure of normal rats to iron in vivo increased expression of the isoform of DMT1

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Burda, Pavel, Nikola Curik, Monika Horvathova, Vladimir Divoky, and Tomas Stopka. "Divalent Metal Transporter 1 (DMT1) Regulates EPO Receptor Gene Expression Via GATA-1." Blood 120, no. 21 (2012): 991. http://dx.doi.org/10.1182/blood.v120.21.991.991.

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Abstract Abstract 991 Introduction: Erythroid differentiation and iron metabolism are interconnected processes in order to produce sufficient numbers of appropriately hemoglobinized red cells. Patients carrying mutations of divalent metal transporter DMT1 display severe microcytic anemia and iron overload. In vivo, this defect can be partially rescued by stimulation of erythropoiesis by erythropoetin (EPO). In vitro, addition of EPO together with iron-saturated salicylaldehyde isonicotinoyl hydrazone (Fe-SIH, a non-transferrin iron donor) to the cultures significantly improved the growth of pa

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Glass, Jonathan, Yi Chen, Yuxiang Ma, Mary Yeh, and Kwo-yih Yeh. "The DMT1 Associated Protein (DAP) Regulates Iron Uptake by Erythroid Cells." Blood 104, no. 11 (2004): 53. http://dx.doi.org/10.1182/blood.v104.11.53.53.

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Abstract The divalent metal transporter 1 (DMT1) is essential for cellular iron uptake both in the intestine and in erythroid cells. We have previously shown that with iron feeding the DMT1 expressed on the brush border membrane (BBM) of the intestine undergoes endocytosis (Am. J. Physiol. 283, G965, 2002). Using the yeast two-hybrid system we have isolated a cDNA clone encoding a protein of 526-amino acid residues with a calculated molecular mass of 60 kDa, which interacts with the C-terminus of DMT1 expressed from the IRE containing mRNA (Blood ,100, 7a, 2002). The ORF of the rat protein has

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Shawki, Ali, Sarah R. Anthony, Yasuhiro Nose, et al. "Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese." American Journal of Physiology-Gastrointestinal and Liver Physiology 309, no. 8 (2015): G635—G647. http://dx.doi.org/10.1152/ajpgi.00160.2015.

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Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1int/int). DMT1int/intmice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1int/intmice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcid

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