Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Iron(II) exacerbates the effects of oxidative stress via the Fenton reaction. A number of human diseases are associated with iron accumulation including ischemia-reperfusion injury, inflammation and certain neurodegenerative diseases. The functional properties and localization in plasma membrane of cells and endosomes suggest an important role for the divalent metal transporter DMT1 (also known as DCT1 and Nramp2) in iron transport and cellular iron homeostasis. Although iron metabolism is strictly controlled and the activity of DMT1 is central in controlling iron homeostasis, no regulatory mechanisms for DMT1 have been so far identified. Our studies show that the activity of DMT1 is modulated by compounds that affect its redox status. We also show that both iron and zinc are transported by DMT1 when expressed in Xenopus laevis oocytes. Radiotracer uptake and electrophysiological measurements revealed that H(2)O(2) and Hg(2+) treatments result in substantial inhibition of DMT1. These findings may have a profound relevance from a physiological and pathophysiological standpoint.
Aizenman,
Oxygen free radicals regulate NMDA receptor function via a redox modulatory site.
1990, Pubmed
Aizenman,
Oxygen free radicals regulate NMDA receptor function via a redox modulatory site.
1990,
Pubmed Babior,
Oxygen-dependent microbial killing by phagocytes (first of two parts).
1978,
Pubmed Bannon,
Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells.
2003,
Pubmed Brazzolotto,
Human cytoplasmic aconitase (Iron regulatory protein 1) is converted into its [3Fe-4S] form by hydrogen peroxide in vitro but is not activated for iron-responsive element binding.
1999,
Pubmed Burdo,
Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat.
2001,
Pubmed Burdo,
Cellular distribution of iron in the brain of the Belgrade rat.
1999,
Pubmed Caltagirone,
Modulation of cellular iron metabolism by hydrogen peroxide. Effects of H2O2 on the expression and function of iron-responsive element-containing mRNAs in B6 fibroblasts.
2001,
Pubmed Canonne-Hergaux,
Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron.
1999,
Pubmed Dexter,
Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease.
1989,
Pubmed Fantini,
Deferoxamine prevents lipid peroxidation and attenuates reoxygenation injury in postischemic skeletal muscle.
1993,
Pubmed Finkel,
Oxidants, oxidative stress and the biology of ageing.
2000,
Pubmed Finkel,
Oxygen radicals and signaling.
1998,
Pubmed Fleming,
Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.
1998,
Pubmed Fleming,
Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1.
1999,
Pubmed Fridovich,
Superoxide radical and superoxide dismutases.
1995,
Pubmed Gerlach,
Altered brain metabolism of iron as a cause of neurodegenerative diseases?
1994,
Pubmed Goswami,
Iron transport: emerging roles in health and disease.
2002,
Pubmed Gruenheid,
Identification and characterization of a second mouse Nramp gene.
1995,
Pubmed Gunshin,
Cloning and characterization of a mammalian proton-coupled metal-ion transporter.
1997,
Pubmed
,
Xenbase He,
Time-course and localization of transferrin receptor expression in the substantia nigra of 6-hydroxydopamine-induced parkinsonian rats.
1999,
Pubmed Hubert,
Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function.
2002,
Pubmed Jellinger,
The role of iron in neurodegeneration: prospects for pharmacotherapy of Parkinson's disease.
1999,
Pubmed Kaltschmidt,
Activation of NF-kappa B by reactive oxygen intermediates in the nervous system.
1999,
Pubmed Kaur,
Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease.
2003,
Pubmed Kim,
Hydrogen peroxide-induced current in Xenopus oocytes: current characteristics similar to those induced by the removal of extracellular calcium.
2002,
Pubmed
,
Xenbase Knöpfel,
Characterization of an integral protein of the brush border membrane mediating the transport of divalent metal ions.
2000,
Pubmed Lee,
The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms.
1998,
Pubmed McCord,
Oxygen-derived free radicals in postischemic tissue injury.
1985,
Pubmed McCord,
Oxygen-derived radicals: a link between reperfusion injury and inflammation.
1987,
Pubmed Omar,
Prevention of postischaemic lipid peroxidation and liver cell injury by iron chelation.
1989,
Pubmed Pantopoulos,
Differences in the regulation of iron regulatory protein-1 (IRP-1) by extra- and intracellular oxidative stress.
1997,
Pubmed Pantopoulos,
Activation of iron regulatory protein-1 by oxidative stress in vitro.
1998,
Pubmed Ponka,
Function and regulation of transferrin and ferritin.
1998,
Pubmed Qian,
Transferrin-bound iron uptake by the cultured cerebellar granule cells.
1998,
Pubmed Qian,
Cerebellar granule cells acquire transferrin-free iron by a carrier-mediated process.
1999,
Pubmed Richardson,
The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells.
1997,
Pubmed Rolfs,
Intestinal expression of genes involved in iron absorption in humans.
2002,
Pubmed Ruppersberg,
Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.
1991,
Pubmed
,
Xenbase Sacher,
Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes.
2001,
Pubmed
,
Xenbase Stadtman,
Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions.
1993,
Pubmed Thannickal,
Activation of an H2O2-generating NADH oxidase in human lung fibroblasts by transforming growth factor beta 1.
1995,
Pubmed Trotti,
Differential modulation of the uptake currents by redox interconversion of cysteine residues in the human neuronal glutamate transporter EAAC1.
1997,
Pubmed
,
Xenbase Trotti,
SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter.
1999,
Pubmed
,
Xenbase Trotti,
Neuronal and glial glutamate transporters possess an SH-based redox regulatory mechanism.
1997,
Pubmed Trotti,
Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration?
1998,
Pubmed van der Kraaij,
Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine.
1988,
Pubmed van Iwaarden,
What we can learn from the effects of thiol reagents on transport proteins.
1992,
Pubmed
