Separate pathways for cellular uptake of ferric and ferrous iron

Conrad, Marcel E.; Umbreit, Jay N.; Moore, Elizabeth; Hainsworth, Lucille N.; Porubcin, Michael; Simovich, Marcia J.; Nakada, Marian T.; Dolan, Kevin G.; Garrick, Michael D.

doi:10.1152/ajpgi.2000.279.4.g767

Cited by 113 publications

(83 citation statements)

References 39 publications

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“…A polyclonal antibody to DMT-1 was raised in rabbits to the sequence of amino acids 325-339 (KTNEQVVEVCTNTSS), called sequence I, utilizing Ribi adjuvant as described previously [2]. This antibody detected only bands corresponding to DMT-1 on Western blots of whole cell lysates (Fig.…”

Section: Materials and Methods Antibodiesmentioning

confidence: 99%

“…The Western blots were performed as described previously [2]. In brief, samples were electrophoresed on 10% acrylamide SDS gels and transferred to Immobilon-P (Millipore, Burlington, MA).…”

Section: Western Blotsmentioning

confidence: 99%

“…The antibody has previously been described and reacts with both the large molecular weight glycosylated form of the protein and with the 60 kD minimally glycosylated form [2]. The reactivity on both staining as well as on Western blots could be eliminated by preincubation with the immunogen peptide.…”

Section: Immunofluorescence Localization Of Dmt-1mentioning

confidence: 99%

“…The ferric iron pathway exclusively transports ferric iron, but the ferrous pathway may be used for a variety of metals, the most prominent of which is Mn. The two pathways, while independent at the luminal surface, are thought to interact inside the cell [2]. Iron leaves the intestinal mucosal cell bound to transferrin and, except in some pathological conditions, iron is not available in the ionic form.…”

Section: Introductionmentioning

confidence: 99%

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Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

et al. 2003

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There are two pathways for inorganic iron uptake in the intestine, the ferric pathway, mediated by the key protein mobilferrin, and the ferrous pathway, mediated by DMT-1. Previous studies reported that the amount of DMT-1 increased in the intestinal mucosa in iron deficiency and the increase was seen in the apical portion of the villus of the duodenal mucosa. Mobilferrin did not quantitatively increase but became localized at the cell membrane. However, studies on fresh tissue have not previously been performed and the localization to the microvillae has not been demonstrated. In order to more definitively localize these proteins immunofluorescent and electron microscopic studies were undertaken. Samples were also subjected to biochemical analysis and Western analysis. In iron-deficient animals both DMT-1 and Mobilferrin were concentrated in the apical surface of the villae. Electron microscopy revealed that the majority of this increase in the amount of these proteins near the luminal surface was due to increased binding of the proteins to mucin in vesicles near the surface. A significant portion of the iron transport proteins was localized in the goblet cells and outside the cell in the luminal mucin, as demonstrated by immunofluorescence, electron microscopy, and isolation of the mucin by cesium chloride gradient centrifugation and Western analysis. A new model for the transport of metal ions was suggested. The metal transport proteins travel from vesicles inside the cell out to the lumen mucin. This increases the surface area and allows a greater portion of the lumen contents to be exposed to the binding proteins. Once the metal is bound to the externalized protein it is internalized into the cell. This explains many of the unique properties of the iron-binding proteins and suggests that it may be a more general model for the absorption of other nutrients. Am. J. Hematol. 74:32-45, 2003.

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Section: Materials and Methods Antibodiesmentioning

confidence: 99%

“…The Western blots were performed as described previously [2]. In brief, samples were electrophoresed on 10% acrylamide SDS gels and transferred to Immobilon-P (Millipore, Burlington, MA).…”

Section: Western Blotsmentioning

confidence: 99%

Section: Immunofluorescence Localization Of Dmt-1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

et al. 2003

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“…Conflicting arguments exist over whether Tf receptors are present or absent in the entrerocyte (Parmley et al, 1985;Pietrangelo et al, 1992(Oates et al, 2000. Studies by Conrad et al indicate that Mn shares the ferrous iron transport mechanism (DMT1) but no the ferric pathway (β 3 -integran and mobilferrin) (Conrad et al, 2000).…”

Section: Divalent Metal Transporter (Dmt1) In Mn Transportmentioning

confidence: 99%

Manganese neurotoxicity: A focus on the neonate

Erikson

Thompson

Aschner

et al. 2007

Pharmacology & Therapeutics

224

141

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Manganese (Mn) is an essential trace metal found in all tissues, and it is required for normal amino acid, lipid, protein, and carbohydrate metabolism. While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is more prevalent. The brain appears to be especially vulnerable. Mn neurotoxicity is most commonly associated with occupational exposure to aerosols or dusts that contain extremely high levels (> 1-5 mg Mn/m 3 ) of Mn, consumption of contaminated well water, or parenteral nutrition therapy in patients with liver disease or immature hepatic functioning such as the neonate. This review will focus primarily on the neurotoxicity of Mn in the neonate. We will discuss putative transporters of the metal in the neonatal brain and then focus on the implications of high Mn exposure to the neonate focusing on typical exposure modes (e.g., dietary and parenteral). Although Mn exposure via parenteral nutrition is uncommon in adults, in premature infants, it is more prevalent, so this mode of exposure becomes salient in this population. We will briefly review some of the mechanisms of Mn neurotoxicity and conclude with a discussion of ripe areas for research in this underreported area of neurotoxicity.

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Interactions between Iron and Other Metals

Crichton

2009

Iron Metabolism

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Separate pathways for cellular uptake of ferric and ferrous iron

Cited by 113 publications

References 39 publications

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

Manganese neurotoxicity: A focus on the neonate

Interactions between Iron and Other Metals

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