Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins

Frazer, David M.; Vulpe, Christopher D.; McKie, Andrew T.; Wilkins, Sarah J.; Trinder, Deborah; Cleghorn, Geoffrey J.; Anderson, Gregory J.

doi:10.1152/ajpgi.2001.281.4.g931

Cited by 123 publications

(101 citation statements)

References 34 publications

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“…The cytoplasmic Fe(II) can efflux from the enterocyte at the basolateral surface via the Fe(II) permease Fpn. As noted above, this efflux is dependent on the ferroxidation due to Hp (27,29,54,61,73,74); in plasma, the product of this coupled permeation-oxidation is likely ferric Tf. The redox cycling in Ft (Fig.…”

Section: Ferrireductases and Ferroxidases Are The Iron Metabolic Pathwaymentioning

confidence: 91%

Redox Cycling in Iron Uptake, Efflux, and Trafficking

Kosman

2010

Journal of Biological Chemistry

104

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Aerobic organisms are faced with a dilemma. Environmental iron is found primarily in the relatively inert Fe(III) form, whereas the more metabolically active ferrous form is a strong pro-oxidant. This conundrum is solved by the redox cycling of iron between Fe(III) and Fe(II) at every step in the iron metabolic pathway. As a transition metal ion, iron can be "metabolized" only by this redox cycling, which is catalyzed in aerobes by the coupled activities of ferric iron reductases (ferrireductases) and ferrous iron oxidases (ferroxidases).Following the first crystallization of a protein, jack bean urease, reported by Sumner in 1926 (1), the evolution of protein chemistry remained a slow process, hampered by limitations in techniques for protein resolution and analysis. Not surprisingly, many proteins obtained in relatively pure form were those with prosthetic metal ion groups that imparted a visible absorbance to guide the purification. Some were copper proteins whose Cu(II) spectral properties gave their protein host a greenish blue to bright blue hue. Two of these were from mammalian whole blood: hemocuprein (cupric species from erythrocytes, superoxide dismutase) and ceruloplasmin (cerulean blue species from plasma). Superoxide dismutase was first isolated in 1938 by Mann and Keilin (5); Cp 2 was first isolated in 1948 by Holmberg and Laurell (6). Both proteins play essential roles in aerobic homeostasis. In the case of ceruloplasmin and the other copper proteins that share its substrate specificity, this role is to manage the redox state of iron in the metabolism of this essential yet potentially cytotoxic transition metal ion. These proteins, all of which are members of the MCO family (7-9), and the mechanism by which they provide this function are a focus of this minireview.

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Section: Ferrireductases and Ferroxidases Are The Iron Metabolic Pathwaymentioning

confidence: 91%

Redox Cycling in Iron Uptake, Efflux, and Trafficking

Kosman

2010

Journal of Biological Chemistry

104

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“…Immunolocalization experiments in IEC-6 cells isolated from the small intestine have identified hephaestin in the perinuclear region of the cells. Although this protein has also been detected on the plasma membrane, the labeling was weak and the exact region of membrane to which it is localized was not determined (Frazer et al, 2001;Simovich et al, 2002). It has been suggested that this protein may mediate the intracellular transport of Fe, and possibly Cd 2+ , to MTP1.…”

Section: Mimicry and Intestinal Transport Of CD 2+mentioning

confidence: 99%

Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

667

460

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Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

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“…The iron can then be either stored in an inert form bound to ferritin (22), used by the cell, or exported from the enterocyte via a pathway that requires the ferroxidase hephaestin (23,24) and the basolateral iron transporter ferroportin (25). Iron is transported in the serum bound to transferrin, which interacts with transferrin receptor 1 (TfR1) on the plasma membrane of cells that take up iron.…”

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confidence: 99%

Overexpression of Cellular Iron Import Proteins Is Associated with Malignant Progression of Esophageal Adenocarcinoma

Boult

Roberts

Brookes

et al. 2008

Clinical Cancer Research

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112

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Purpose:There is growing evidence that iron is important in esophageal adenocarcinoma, a cancer whose incidence is rising faster than any other in theWestern world. However, how iron mediates carcinogenesis at the molecular level remains unclear. In this study, we investigated the expression of iron transport proteins involved in cellular iron import, export, and storage in the premalignant lesion Barrett's metaplasia and esophageal adenocarcinoma. Experimental Design: Perls' staining was used to examine iron deposition in tissue. mRNA expression in samples of Barrett's metaplasia matched with esophageal adenocarcinoma and samples of Barrett's metaplasia without evidence of adenocarcinoma were examined by real-time PCR. Semiquantitative immunohistochemistry was used to examine cellular localization and protein levels. The effect of iron loading on cellular proliferation and iron transporter expression was determined in esophageal cell lines OE33 and SEG-1 using a bromodeoxyuridine assay and real-time PCR, respectively. Results: In the progression of Barrett's metaplasia to adenocarcinoma, there was overexpression of divalent metal transporter 1 (DMT1), transferrin receptor 1, duodenal cytochrome b, ferroportin, and H-ferritin, and these changes were associated with increased iron deposition. Overexpression of DMT1was further associated with metastatic adenocarcinoma. Iron loading OE33 and SEG-1 cells caused increased cellular proliferation, which was associated with increased H-ferritin and decreased transferrin receptor 1and DMT1expression. Conclusions: Progression to adenocarcinoma is associated with increased expression of iron import proteins. These events culminate in increased intracellular iron and cellular proliferation. This may represent a novel mechanism of esophageal carcinogenesis.

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Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins

Cited by 123 publications

References 34 publications

Redox Cycling in Iron Uptake, Efflux, and Trafficking

Redox Cycling in Iron Uptake, Efflux, and Trafficking

Molecular and ionic mimicry and the transport of toxic metals

Overexpression of Cellular Iron Import Proteins Is Associated with Malignant Progression of Esophageal Adenocarcinoma

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