A Novel Duodenal Iron-Regulated Transporter, IREG1, Implicated in the Basolateral Transfer of Iron to the Circulation

McKie, Andrew T.; Marciani, P.; Rolfs, Andreas; Brennan, Karen; Wehr, Kristina; Barrow, Dalna; Miret, Silvia; Bomford, Adrian; Peters, Timothy J.; Farzaneh, Farzin; Hediger, Matthias A.; Hentze, Matthias W.; Simpson, Robert J.

doi:10.1016/s1097-2765(00)80425-6

Cited by 1,291 publications

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References 37 publications

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“…Up-regulation of FPN expression at mRNA level has already been reported in duodenums isolated from mice exposed to hypoxia or fed on iron-deficient diet [3]. Treatment of CaCo2 cells with iron reduces FPN transcriptional rates while desferrioxamine treatment results in the opposite effect [16].…”

Section: Discussionmentioning

confidence: 86%

Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice

Chiabrando

Fiorito

Marro

et al. 2013

Blood Cells, Molecules, and Diseases

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Here we show that, during experimentally-induced acute anemia in mice, FPN is regulated at transcriptional level in a cell-specific manner. FPN mRNA level increases in duodenum and spleen macrophages, whereas it does not change in liver and is strongly down-regulated in erythroid precursors. These results were confirmed in Caco2 Raw264.7 and K562 cells treated with a hypoxic stimulus. Moreover, we found a differential expression of HIF1α and HIF2α in cells and tissues that might account for the specificity of FPN regulation.Thus, hypoxia, by directly controlling hepcidin and its target FPN, orchestrates a complex regulatory network aimed at ensuring rapid iron recovery from the periphery and efficient iron utilization in the erythroid compartment.

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Section: Discussionmentioning

confidence: 86%

Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice

Chiabrando

Fiorito

Marro

et al. 2013

Blood Cells, Molecules, and Diseases

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show abstract

“…Translational control mechanisms are known to be operative in iron homeostasis. The regulation of the translation of ferritin and ferroportin 1 by iron (McKie et al, 2000;Crichton et al, 2002) and the arrest of ceruloplasmin translation in macrophages exposed to IFN-γ (Mazumder et al, 2005) reflect changes in the initiation of translation and release of the non-translating mRNAs from polysomes. Zip5 mRNA remains associated with polysomes during zinc deficiency and inhibitors of the proteasome and lysosome did not result in the reaccumulation of ZIP5 protein in VYS explant cultures.…”

Section: Discussionmentioning

confidence: 99%

Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5)

Weaver

Dufner-Beattie

Kambe

et al. 2007

BCHM

148

171

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Dietary zinc deficiency in mice is accompanied by enhanced expression of the zinc uptake transporter Slc39a4 (Zip4) and repressed expression of Slc39a5 (Zip5) in tissues which regulate zinc homeostasis (intestine, pancreas and visceral yolk sac). Herein, mechanisms controlling this differential expression were investigated. The induction of Zip4 mRNA during zinc deficiency, and its repression in response to zinc repletion were found to reflect changes in Zip4 mRNA stability and not changes in the relative rate of transcription of this gene. During zinc deficiency, ZIP4 protein levels are increased and this protein is localized on the apical membranes. Administration of an oral gavage of zinc caused ZIP4 internalization and degradation in enterocytes and visceral endoderm cells. Similarly, ZIP4 is induced by zinc deficiency in cultured mouse Hepa cells and is rapidly degraded in response to added zinc. Zip5 mRNA abundance does not change in response to zinc, but the translation of this mRNA was found to be zinc-responsive. During zinc deficiency, Zip5 mRNA remains associated with polysomes, while the protein is internalized and degraded in enterocytes, acinar cells and endoderm cells. After zinc-gavage, ZIP5 is rapidly resynthesized and targeted to the basolateral membranes of these cell types.

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“…In mice, a mutation in hephastin (the sex-linked anemia) cannot release iron across the basolateral membrane. Another protein, ferroportin [40], appears to be the actual transmembrane transporter. Hephaestin and ferroportin appear to respond to systemic rather than local (i.e., duodenal) iron levels and may exercise control of iron uptake at that stage [41].…”

Section: Physiology Of Ironmentioning

confidence: 99%

Iron deficiency: A concise review

2005

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Iron deficiency is a major worldwide health problem. There is recent evidence that the anemia is only the last manifestation of the syndrome and that symptoms occur before the anemia is manifest. Advances in outlining the physiology of iron deficiency have been made, gaps remain in the current understanding. While oral iron supplement remains the mainstay, some indications for the intravenous administration have developed. This review will highlight the epidemiology, physiology, clinical presentation, and treatment options. Am.

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A Novel Duodenal Iron-Regulated Transporter, IREG1, Implicated in the Basolateral Transfer of Iron to the Circulation

Cited by 1,291 publications

References 37 publications

Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice

Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice

Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5)

Iron deficiency: A concise review

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