<i>In Vitro</i> Absorption of Radioiron by Everted Pouches of Rat Intestine

Brown, E. B.; Justus, B

doi:10.1152/ajplegacy.1958.194.2.319

Cited by 65 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DMT1 functions as a Fe(Ⅱ)/proton symporter [96] and is highly expressed in the duodenum during iron deficiency [99] . This is consistent with the duodenum being the principal site of iron absorption [100] and the least alkaline section of the small intestine due to the close proximity to acidic gastric secretions. Ultimately, Fe(Ⅲ) is also transported by DMT1 after reduction to Fe(Ⅱ) by DcytB [101] , although the physiological significance of this pathway is the subject of continued debate [102,103] .…”

Section: A Possible Role For Dmt1?supporting

confidence: 86%

Mechanisms of heme iron absorption: Current questions and controversies

West¹,

Oates²

2008

WJG

213

156

View full text Add to dashboard Cite

THE IMPORTANCE OF DIETARY IRON AND HEMEIron is a vitally important element in biological terms (for review see [1] ). Iron is a transition metal with the ability to readily accept and donate electrons, allowing it to function as an oxidant or reductant in a large number of biochemical reactions. In mammals, iron is notably required for oxygen transport as a component of hemoglobin, DNA synthesis as a component of ribonucleotide reductase, and as an electron acceptor/ donor in the cytochromes that are essential for energy transduction. Currently, iron deficiency is the most common diet related health problem in the world [2] , and the effects on human health are wide ranging. Iron deficiency manifests as anaemia in up to 2 billion people, impairs physical and mental development in children, and can exacerbate many other health problems.Heme is a biologically important iron containing compound and a key source of dietary iron. Historically, it was doubted that heme iron could be absorbed by the enterocyte and it was not until 1955 that the absorption of heme-derived iron was demonstrated for the first time [3] . Currently, the importance of heme iron in the diet cannot be underestimated. Studies estimate that in Western societies, iron derived from heme sources such as myoglobin and hemoglobin make up twothirds of the average person's total iron stores despite only constituting one-third of the iron that is actually ingested [4][5][6] . This likely explains why vegetarians are more prone to iron deficiency than those who regularly consume red meat [7] . T h e r e l a t ive i m p o r t a n c e o f d i e t a r y h e m e i s attributable to its high bioavailability compared with AbstractIron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heme absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heme transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a nonheme iron transport protein may be required for heme iron absorption and discuss the experiences of our laboratory in examining this hypothesis.

show abstract

Section: A Possible Role For Dmt1?supporting

confidence: 86%

Mechanisms of heme iron absorption: Current questions and controversies

West¹,

Oates²

2008

WJG

213

156

View full text Add to dashboard Cite

show abstract

“…In addition, when the duodenum was divided into three 1-cm segments, hepcidin concentration was highest in the most proximal portion of the duodenum where iron uptake and ferroportin concentrations are also the highest (Figure 6). 16 Hepcidin content in the liver, another site of ferroportin expression, was lower than in the spleen and duodenum and not significantly higher than in blood, but it was higher than in all other organs measured-the intestine, lung, muscle, and paw ( Figure 5). By inspection, the washout of blood from the liver was highly effective, so it is unlikely that the high hepcidin concentrations in this organ were due to background blood.…”

Section: Org Frommentioning

confidence: 90%

“…16 The lower accumulation of hepcidin in the liver is probably due to the lower ferroportin expression in numerically dominant hepatocytes compared with hepatic macrophages. If so, the relatively lower ferroportin activity in hepatocytes could help explain why these cells (rather than the macrophages) preferentially accumulate iron in most iron overload diseases.…”

Section: Discussionmentioning

confidence: 99%

Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs

Rivera

Nemeth

Gabayan

et al. 2005

Blood

279

231

View full text Add to dashboard Cite

Hepcidin is the principal iron regulatory hormone and its overproduction contributes to anemia of inflammation (AI). In vitro, hepcidin binds to and induces the degradation of the exclusive iron exporter ferroportin. We explored the effects and distribution of synthetic hepcidin in the mouse. A single intraperitoneal injection of hepcidin caused a rapid fall of serum iron in a dose-dependent manner, with a 50-g dose resulting in iron levels 80% lower than in control mice. The full effect was seen within only 1 hour, consistent with a blockade of iron export from tissue stores and from macrophages involved in iron recycling. Serum iron remained suppressed for more than 48 hours after injection. Using radiolabeled hepcidin, we demonstrated that the serum concentration of hepcidin at the 50-

show abstract

“…Therefore, in the present study we developed and verified an antibody against rat HFE in order to assess the sub-cellular location of the protein in enterocytes of the proximal small intestine, the primary site of iron absorption (Brown and Justus 1958), in iron-deficient and control conditions. Double-labelling experiments were performed with HFE and various sub-cellular markers; lactase for the microvillus membrane (Quaroni and Isselbacher 1985), F-actin for the terminal web (Hull and Staehelin 1979;Leeson 1982), EEA1 for early endosomes (Mu et al 1995), Lamp1/lgp120 for lysosomes (Howe et al 1988;Lewis et al 1985) and transferrin receptor (TfR), which is capable of physically associating with HFE (Feder et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Haemochromatosis protein is expressed on the terminal web of enterocytes in proximal small intestine of the rat

West

Thomas

Sadlier

et al. 2005

Histochem Cell Biol

View full text Add to dashboard Cite

The haemochromatosis protein (HFE) is an important regulator of body iron stores. In the liver, HFE is required for appropriate expression of hepcidin, a humoral mediator of iron absorption. HFE is also present in enterocytes, though its function in the intestine is unknown; it is not intrinsically required for iron absorption, but can augment iron absorption when over-expressed-independent of hepcidin regulation by the liver. In this study, an antibody was raised against rat HFE and validated by enzyme-linked immunosorbent assay, Western blot and quenching of antibody function by the immunising peptide. The sub-cellular location of HFE in enterocytes of iron-deficient and control rats was determined by double-labelling experiments with markers for the microvillus membrane, terminal web, early endosomes, lysosomes and the transferrin receptor. Parallel studies were performed for the primary iron absorption protein, divalent metal transporter 1 (DMT1). HFE co-localised exclusively with the terminal web of intestinal enterocytes. HFE expression was increased in iron deficiency, consistent with a second regulatory role for HFE in iron absorption, independent of hepcidin from the liver. DMT1 was localised primarily on the microvillus membrane, but did partially co-localise with HFE raising the possibility that the two proteins may interact to regulate iron absorption.

show abstract

In Vitro Absorption of Radioiron by Everted Pouches of Rat Intestine

Cited by 65 publications

References 0 publications

Mechanisms of heme iron absorption: Current questions and controversies

Mechanisms of heme iron absorption: Current questions and controversies

Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs

Haemochromatosis protein is expressed on the terminal web of enterocytes in proximal small intestine of the rat

Contact Info

Product

Resources

About