Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload

Zoller, Heinz; Koch, Robert; Theurl, Igor; Obrist, Peter; Pietrangelo, Antonello; Montosi, Giuliana; Haile, David J.; Vogel, Wolfgang; Weiß, Günter

doi:10.1053/gast.2001.24033

Cited by 266 publications

(207 citation statements)

References 32 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: 61%

“…The duodenal expression of these iron transporters has been studied in only a few patients with nonhemochromatosis chronic liver disease. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies indicate that the protein levels of these iron transporters parallel the changes observed in the gene expression of these molecules. 14,15,19,29 Therefore, the expression of these iron molecules was assessed by ribonuclease protection assays only.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of DMT1 or Ireg1 in the 46 subjects with cirrhosis did not correlate with hemoglobin levels as it did in controls, suggesting that the degree of anemia was not a significant factor causing increased expression of these iron transport genes in cirrhosis. Iron deficiency-an important cause of increased iron absorption and intestinal iron transporter expression 19,22,28 -is common in patients with cirrhosis and frequently is occult. 10,31 Iron deficiency was diagnosed in four subjects with cirrhosis and the expression of the iron transport genes in these four subjects was similar to that observed in the iron-deficient controls.…”

Section: Discussionmentioning

confidence: 99%

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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: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…Studies suggest that the divalent metal transporter 1 (DMT1) is a transporter for Fe and Pb in the small intestine and regulated in accord with Fe status. This protein is higher in iron deficiency and lower in iron overload in villous enterocytes (Canonne-Hergaux et al, 1999;Fleming et al, 1997;Gunshin et al, 1997;Oates et al, 2000;Trinder et al, 2000;Zoller et al, 2001). Therefore a plausible system could exist where variations of Fe stores within the normal range do not cause a significant increase in Pb absorption, but during periods of Fe deficiency, the level of DMT1 becomes high enough to allow for increased Pb absorption.…”

Section: Discussionmentioning

confidence: 99%

Iron supplement prevents lead-induced disruption of the blood–brain barrier during rat development

Wang

Luo

Zheng

et al. 2007

Toxicology and Applied Pharmacology

102

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Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 μg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO 4 solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p<0.05) and brain tissues by 1.5-2.0-folds (p<0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p<0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultrastructure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications.

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Use of Zebrafish Models for the Analysis of Human Disease

Zhu

Zon

2002

CP Human Genetics

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The zebrafish has emerged as a powerful animal model for human diseases. While it has long informed us about the biology of early development, it has recently come into favor for the investigation of clinically relevant problems. Genes conserved from fish to humans can be rapidly analyzed using the zebrafish embryo in what is essentially a transparent in vivo assay. This unit describes methodologies including genetic screening, targeted knockdowns, ectopic overexpression, and transgenesis.

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Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload

Cited by 266 publications

References 32 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

Iron supplement prevents lead-induced disruption of the blood–brain barrier during rat development

Use of Zebrafish Models for the Analysis of Human Disease

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