Iron Imports. V. Transport of iron through the intestinal epithelium

Ma, Yuxiang; Yeh, Mary; Yeh, Kwo–Yih; Glass, Jonathan

doi:10.1152/ajpgi.00489.2005

Cited by 51 publications

(56 citation statements)

References 26 publications

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“…This mucosal block describes the ability of an initial dose of ingested iron to block iron absorption of a second dose given 2-4 h later. The exact mechanism of this mucosal block is unknown, but in vitro and animal studies suggest the involvement of inhibition of enterocyte import of ingested iron by the ferrous iron transporter divalent metal transporter 1 at the brush border secondary to an increase in intracellular iron (22 ) or a reduction in function of divalent metal transporter 1 and/or the function of the basolateral iron exporter ferroportin secondary to an increase in circulating hepcidin (23)(24)(25)(26). Importantly, the latter mechanism is supported by recent human studies showing an inverse relation between intestinal iron uptake and circulating hepcidin concentrations (9,16 ).…”

Section: Discussionmentioning

confidence: 99%

Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations

Schaap¹,

Hendriks

Kortman³

et al. 2013

Clinical Chemistry

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BACKGROUND:The iron-regulating hormone hepcidin is a promising biomarker in the diagnosis of iron disorders. Concentrations of hepcidin have been shown to increase during the day in individuals who are following a regular diet. It is currently unknown whether these increases are determined by an innate rhythm or by other factors. We aimed to assess the effect of dietary iron on hepcidin concentrations during the day.

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Section: Discussionmentioning

confidence: 99%

Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations

Schaap¹,

Hendriks

Kortman³

et al. 2013

Clinical Chemistry

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“…Transcytosis is definitely the stage about which the least is known. Although there is evidence that DMT1 moves with the iron [32], Núñez' group [37] recently reminded us that such data can also account for a loss of iron uptake after an iron challenge, traditionally called the mucosal block [54]. Earlier, there were similar observations in Caco2 cells supporting this interpretation [46].…”

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confidence: 99%

Human iron transporters

Garrick

2010

Genes Nutr

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Human iron transporters manage iron carefully because tissues need iron for critical functions, but too much iron increases the risk of reactive oxygen species. Iron acquisition occurs in the duodenum via divalent metal transporter (DMT1) and ferroportin. Iron trafficking depends largely on the transferrin cycle. Nevertheless, nondigestive tissues have a variety of other iron transporters that may render DMT1 modestly redundant, and DMT1 levels exceed those needed for the just-mentioned tasks. This review begins to consider why and also describes advances after 2008 that begin to address this challenge.

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“…Nevertheless, there is scant but convincing evidence that FPN (26,44) and DMT1 (6) are located in both the apical and basolateral domains. In iron-starved rats and Caco-2 cells, DMT1 shows a marked brush border distribution, but iron feeding promotes a fast (10 -400 min) internalization of DMT1 into the apical cytoplasm (28,29). This redistribution was interpreted as evidence of a process in which vesicles containing DMT1-iron could fuse with and pass the iron to vesicles containing apo-transferrin (28,29).…”

mentioning

confidence: 99%

“…In iron-starved rats and Caco-2 cells, DMT1 shows a marked brush border distribution, but iron feeding promotes a fast (10 -400 min) internalization of DMT1 into the apical cytoplasm (28,29). This redistribution was interpreted as evidence of a process in which vesicles containing DMT1-iron could fuse with and pass the iron to vesicles containing apo-transferrin (28,29). Nevertheless, the possibility of a regulatory mechanism that involves the movement of transporters in response to iron was left open.…”

mentioning

confidence: 99%

Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1

Núñez

Tapia

Rojas³

et al. 2010

American Journal of Physiology-Cell Physiology

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Núñez MT, Tapia V, Rojas A, Aguirre P, Gómez F, Nualart F. Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1. Am J Physiol Cell Physiol 298: C477-C485, 2010. First published December 9, 2009; doi:10.1152/ajpcell.00168.2009.-Intestinal iron absorption comprises the coordinated activity of the influx transporter divalent metal transporter 1 (DMT1) and the efflux transporter ferroportin (FPN). In this work, we studied the movement of DMT1 and FPN between cellular compartments as a function of iron supply. In rat duodenum, iron gavage resulted in the relocation of DMT1 to basal domains and the internalization of basolateral FPN. Considerable FPN was also found in apical domains. In Caco-2 cells, the apical-to-basal movement of cyan fluorescent protein-tagged DMT1 was complete 90 min after the addition of iron. Steady-state membrane localization studies in Caco-2 cells revealed that iron status determined the apical/ basolateral membrane distribution of DMT1 and FPN. In agreement with the membrane distribution of the transporters, 55 Fe flux experiments revealed inward and outward iron fluxes at both membrane domains. Antisense oligonucleotides targeted to DMT1 or FPN inhibited basolateral iron uptake and apical iron efflux, respectively, indicating the participation of DMT1 and FPN in these fluxes. The fluxes were regulated by the iron supply; increased iron reduced apical uptake and basal efflux and increased basal uptake and apical efflux. These findings suggest a novel mechanism of regulation of intestinal iron absorption based on inward and outward fluxes at both membrane domains, and repositioning of DMT1 and FPN between membrane and intracellular compartments as a function of iron supply. This mechanism should be complementary to those based in the transcriptional or translational regulation of iron transport proteins.intestinal iron absorption; divalent metal transporter 1; mucosal block IN THE ABSENCE OF A CONTROLLED excretion mechanism, iron levels in the body are regulated mainly by its passage through the duodenum epithelia. Traditionally, intestinal iron absorption is divided into three sequential steps: the uptake of iron from the intestinal lumen; an intracellular phase, in which iron binds to cytosolic components; and a transfer step, in which iron passes from the cells to the blood plasma. The uptake of iron from the lumen of the intestine is mediated by the Fe 2ϩ -H ϩ cotransporter divalent metal transporter 1 (DMT1) (19).Once inside the enterocyte, iron integrates into a cytosolic pool of weakly bound iron called the labile iron pool (LIP) (16,25). The nature of the LIP-binding counterpart is unknown, but it has been ascribed to diverse low-molecular-weight substances such as phosphate, nucleotides, hydroxyl, amino, and sulfydryl groups (23,36). From the LIP, iron distributes into ferritin and other iron-requiring proteins (15, 24). Iron exit from the enterocyte is mediated by the efflux transporter ferroportin (FPN), the only m...

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Iron Imports. V. Transport of iron through the intestinal epithelium

Cited by 51 publications

References 26 publications

Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations

Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations

Human iron transporters

Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1

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