ArticleThe Journal of nutrition2013
Divalent metal transporter 1 (Dmt1) mediates copper transport in the duodenum of iron-deficient rats and when overexpressed in iron-deprived HEK-293 cells.
Article in The Journal of nutrition, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- The Role of Metal Ions in Mitochondria: From Energy Metabolism to Cell Destiny.Biological trace element research · 2026Review
- Crossroads of iron, copper, and zinc in cancer: a paradox of toxicity and therapy.Molecular biology reports · 2026Review
- Review
- Heme enhances B-cell proliferation and plasma cell formation through reduced p21 and Rb expression.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Cuproptosis and Its Impact on Cardiovascular Health: Mechanisms and Therapeutic Opportunities.Cardiovascular toxicology · 2026Review
- Intestinal Iron Transporters Facilitate Manganese Absorption Under Non-physiological Conditions.Cellular and molecular gastroenterology and hepatology · 2025Article
- Copper ions: The invisible killer of cardiovascular disease (Review).Molecular medicine reports · 2024Review
- Copper Exposure Induced Chicken Hepatotoxicity: Involvement of Ferroptosis Mediated by Lipid Peroxidation, Ferritinophagy, and Inhibition of FSP1-CoQ10 and Nrf2/SLC7A11/GPX4 Axis.Biological trace element research · 2024Article
- Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation.Journal of biomedical science · 2023Article
- Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases.Frontiers in pharmacology · 2023Review
- Oxidation state-specific fluorescent copper sensors reveal oncogene-driven redox changes that regulate labile copper(II) pools.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A direct comparison of divalent metal-ion transporter (DMT1) and hinokitiol, a potential small molecule replacement.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver.Comprehensive Physiology · 2018Review
- Copper supplementation reverses dietary iron overload-induced pathologies in mice.The Journal of nutritional biochemistry · 2018Article
- Intestinal DMT1 Is Essential for Optimal Assimilation of Dietary Copper in Male and Female Mice with Iron-Deficiency Anemia.The Journal of nutrition · 2018Article
- Neurotoxicity Linked to Dysfunctional Metal Ion Homeostasis and Xenobiotic Metal Exposure: Redox Signaling and Oxidative Stress.Antioxidants & redox signaling · 2018Review
- Longitudinal Effects of Iron Deficiency Anemia and Subsequent Repletion on Blood Parameters and the Rate and Composition of Growth in Pigs.Nutrients · 2018Article
- Chemosensitivity of U251 Cells to the Co-treatment of D-Penicillamine and Copper: Possible Implications on Wilson Disease Patients.Frontiers in molecular neuroscience · 2017Article
- Loss of divalent metal transporter 1 function promotes brain copper accumulation and increases impulsivity.Journal of neurochemistry · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Intracellular copper-binding proteins (metallothionein I/II) and a copper exporter (Menkes copper-transporting ATPase) are upregulated in duodenal enterocytes from iron-deficient rats, consistent with copper accumulation in the intestinal mucosa. How copper enters enterocytes during iron deficiency is, however, not clear. Divalent metal transporter 1 (Dmt1), the predominant iron importer in the mammalian duodenum, also transports other metal ions, possibly including copper. Given this possibility and that Dmt1 expression is upregulated by iron deprivation, we sought to test the hypothesis that Dmt1 transports copper during iron deficiency. Two model systems were utilized: the Belgrade (b) rat, expressing mutant Dmt1, and an inducible Dmt1-overexpression cell culture system. Mutant rats (b/b) were fed a semipurified, AIN93G-based control diet and phenotypically normal littermates (+/b) were fed control or iron-deficient diets for ~14 wk. An everted gut sleeve technique and a colorimetric copper quantification assay were utilized to assess duodenal copper transport. The control diet-fed +/b rats had normal hematological parameters, whereas iron-deprived +/b and b/b rats were iron deficient and Dmt1 mRNA and protein levels increased. Importantly, duodenal copper transport was similar in the control +/b and b/b rats; however, it significantly increased (~4-fold) in the iron-deprived +/b rats. Additional experiments in Dmt1 overexpressing HEK-293 cells showed that copper ((64)Cu) uptake was stimulated (∼3-fold) in the presence of an iron chelator. Dmt1 transcript stabilization due to a 3' iron-responsive element was also documented, likely contributing to increased transport activity. In summary, these studies suggest that Dmt1 enhances copper uptake into duodenal enterocytes during iron deprivation.
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