Intestinal expression of genes involved in iron absorption in humans

Rolfs, Andreas; Bonkovsky, Herbert L.; Kohlroser, James G.; McNeal, Kristina; Sharma, Ashish; Berger, Urs V.; Hediger, Matthias A.

doi:10.1152/ajpgi.00371.2001

Cited by 73 publications

(77 citation statements)

References 48 publications

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“…Two groups have reported major increases in the duodenal expression of DMT1 and Ireg1 in a heterogeneous group of C282Y homozygous subjects compared with control subjects with normal iron indices. 19,21 In contrast, our group found no increase in the absolute levels of these iron transporters in a cohort of untreated subjects with HFE-related HHC. Rather, we showed an inappropriate increase in the level of DMT1 and Ireg1 expression for a given SF level.…”

Section: Discussioncontrasting

confidence: 59%

“…Zoller et al 19 reported six subjects with alcoholic and nonalcoholic fatty liver disease with normal biochemical iron indices and found no apparent increase in DMT1 or Ireg1 expression compared with iron-replete controls. Similarly, Rolfs et al 21 found no evidence of up-regulation of DMT1, Ireg1, or hephaestin expression in a small subset of subjects with cirrhosis not due to HHC. The current study investigated a large cohort of patients with cirrhosis of many different etiologies.…”

Section: Discussionmentioning

confidence: 92%

“…19 -22 The duodenal expression of these iron transport genes in cirrhosis, and the potential relation to cirrhosis-associated iron overload, is unknown. However, Rolfs et al 21 reported no increase in DMT1 or Ireg1 expression in a small subset of patients with cirrhosis. We studied the duodenal expression of DMT1, Ireg1, hephaestin, and Dcytb in a cohort of human subjects with cirrhosis.…”

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confidence: 97%

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Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

et al. 2004

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Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), ironregulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Ireg1 expression. In cirrhosis, the expression of DMT1 and Ireg1 was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Ireg1 and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload. (HEPATOLOGY 2004;39: 492-499.)

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 92%

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confidence: 97%

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Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

et al. 2004

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“…It is clear that dietary Fe status has a significant effect on the expression of DMT1 (Anderson et al, 2002;Martini et al, 2002;Rolfs et al, 2002;Wareing et al, 2003;Zoller et al, 2001Zoller et al, , 2002 and the uptake of Cd 2+ in the intestine (Berglund et al, 1994;Choudhury et al, 2001;Flanagan et al, 1978;Fox et al, 1980;Groten et al, 1992). This is particularly evident in pregnant rats (Leazer et al, 2002).…”

Section: Mimicry and Intestinal Transport Of CD 2+mentioning

confidence: 99%

Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

667

460

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Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

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“…Also, DMT1 is involved in iron transport from the endocytic vesicles to the cytosol after the Tf-TfR uptake [26]. Impairment in DMT1 function is associated with alteration in iron metabolism involving iron overload disorder under hemochromatosis [27], iron deficiency anemia [28,29] and neurodegenerative diseases, including Alzheimer's [30] and Parkinson's diseases [31].…”

Section: Divalent Metal Transporter 1 (Dmt1)mentioning

confidence: 99%

Effect of hemochromatosis on manganese neurotoxicity

Alsulimani¹

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ABSTRACT:Manganese (Mn) is an essential element for normal brain function, but excess levels of Mn in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. While Mn is known to share iron transporters for cellular uptake, deficiency in the Hfe (hemochromatosis), a cellular iron regulatory protein, affects the activities of iron transporters and impairs iron metabolism. Previously it was shown that Mn uptake into the brain is increased after intranasal exposure to Mn in Hfe-deficient mice, a mouse model of iron overload hereditary hemochromatosis. However, there is limited information about the effect of Hfe deficiency on Mn toxicity after exposure by other routes. Mn exposure is common through ingestion and inhalation in both environmental and occupational settings. Because Hfe deficiency alters iron transporters, and since Mn shares iron transporters, I hypothesize that Hfe deficiency increases Mn toxicity by modulating Mn uptake from the absorption site and deposition into the target organ for Mn toxicity which is the brain after gastric exposure in drinking water and pulmonary exposure to Mn particles. Specific aims are focused on the effect of Hfe deficiency on 1) the expression levels of metal transporters in the brain, gut and lung including alveolar macrophages, 2) levels of Mn, 3) Mn-associated neurobehavioral impairments, and 4) mechanisms of Mn neurotoxicity. This research will enhance the knowledge of Mn exposure and uptake in Hfe-related hemochromatosis, a prevalent iron disorder in the world.

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Intestinal expression of genes involved in iron absorption in humans

Cited by 73 publications

References 48 publications

Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

Molecular and ionic mimicry and the transport of toxic metals

Effect of hemochromatosis on manganese neurotoxicity

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