Mucosal transferrin and ferritin factors in the regulation of iron absorption

El-Shobaki, F. A.; Rummel, W.

doi:10.1007/bf01851508

Cited by 38 publications

(27 citation statements)

References 18 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the receptor mediated cellular uptake of iron is well known and takes place in all dividing cells, such a mechanism operating in the intestine has not been documented earlier. The results of this study, in conjunction with earlier observations [5,[35][36][37] , allow us to propose a model for intestinal iron absorption whereby., the recycling of transferrin and transferrin receptors enables luminal transferrin bound iron to enter the enterocytes. The receptor density at the absorptive surface, which is inversely proportional to better iron nutritional status, might regulate this iron uptake process.…”

supporting

confidence: 77%

Evidence for a sequential transfer of iron amongst ferritin, transferrin and transferrin receptor during duodenal absorption of iron in rat and human

Kolachala

Sesikeran²,

Nair³

2007

WJG

View full text Add to dashboard Cite

according to the iron nutrition in humans, with intense staining of transferrin receptor observed in iron deficient subjects. CONCLUSION:It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin, transferrin-transferrin receptor and ferritin. INTRODUCTIONIron homeostasis is accomplished by regulating absorption in the proximal small intestine and is regulated according to the body's needs. Failure to maintain this equilibrium leads to pathological conditions resulting in either iron deficiency or iron overload. Iron deficiency anemia remains the most important micronutrient deficiency world wide. Iron is essential because of its unique ability to serve as both an electron donor and acceptor. Because of iron's virtual insolubility and potential toxicity under physiological conditions, special molecules have evolved for its acquisition, transport and storage in soluble, nontoxic form. In humans, heme iron is absorbed more efficiently than non-heme iron [1] . Recent studies demonstrate that non-heme iron is transported into the cell in the ferrous [Fe (Ⅱ)] form, mainly by carrier divalent metal transporter 1 (DMT1)-also known as natural resistance associated macrophage protein 2 (Nramp2) or divalent cation transporter 1 (DCT1) [2] . However, iron absorption is not impaired by mutation of DMT-1, suggesting that DMT-1 is not the only transporter operating within the endosomes of crypt cells. Studies of Conrad et al [3] , showed that ferric iron is absorbed by β3 integrin and mobilferrin pathway which is shared with other nutritional metals .In last few decades, several candidate proteins involved METHODS:Incorporation of 59 Fe into mucosal and luminal proteins was carried out in control WKY rats. The sequential transfer of iron amongst ferritin, transferrin and transferrin receptor was carried out in iron deficient, c o nt ro l a nd iro n overloaded rats. The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections. Human duodenal biopsy (n = 36) collected from subjects with differing iron status were also stained for these proteins. RESULTS:Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa. The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control, iron deficient groups (731.5 ± 191.96 vs 308.3 ± 123.36, 731.5 ± 191.96 vs 256.0 ± 1.19, P < 0.005), while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups (10.9 ± 7.6 vs 0.87 ± 0.79, 11.1 ± 10.3 vs 0.80 ± 1.20, 6.8 ± 4.7 vs 0.61 ± 0.63, P < 0.001). In situ grading of proteins and iron, and their superimposition, suggested the occurrence of a sequential transfer of iron. This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface tran...

show abstract

supporting

confidence: 77%

Evidence for a sequential transfer of iron amongst ferritin, transferrin and transferrin receptor during duodenal absorption of iron in rat and human

Kolachala

Sesikeran²,

Nair³

2007

WJG

View full text Add to dashboard Cite

show abstract

“…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 member of the SLC40 family of transporters and the first reported protein that mediates the exit of iron from cells (30).…”

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

View full text Add to dashboard Cite

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...

show abstract

“…Intestinal transferrin is found in the lumen, on the mucosal cell surface, and inside the mucosal cells of the duodenum and jejunum (14)(15)(16). The increase in intestinal transferrin is correlated with an increase in iron absorption, and this has lead to the hypothesis that transferrin may play a role in mediating iron absorption (13,14,17,18).…”

mentioning

confidence: 99%

“…The increase in intestinal transferrin is correlated with an increase in iron absorption, and this has lead to the hypothesis that transferrin may play a role in mediating iron absorption (13,14,17,18). Several lines of evidence support this idea.…”

mentioning

confidence: 99%