Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse

@article{Vulpe1999HephaestinAC,
  title={Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse},
  author={Chris D. Vulpe and Yien Ming Kuo and Therese L. Murphy and L. Cowley and Candice C. Askwith and Nataliya Libina and Jane Gitschier and Gregory J. Anderson},
  journal={Nature Genetics},
  year={1999},
  volume={21},
  pages={195-199}
}
Iron is essential for many cellular functions; consequently, disturbances of iron homeostasis, leading to either iron deficiency or iron overload, can have significant clinical consequences. [] Key Result We describe here a novel gene, Heph, encoding a transmembrane–bound ceruloplasmin homologue that is mutant in the sla mouse and highly expressed in intestine. We suggest that the hephaestin protein is a multi–copper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation and…

Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency.

TLDR
Iron levels and expression of genes involved in iron uptake and storage in sla mice and C57BL/6J mice fed iron-deficient, iron-overload, or control diets are compared to indicate that Dmt1 can be modulated by the enterocyte iron level, whereas Hephaestin and Ireg1 expression respond to systemic rather than local signals of iron status.

The Multicopper Ferroxidase Hephaestin Enhances Intestinal Iron Absorption in Mice

TLDR
The knockout strains developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and confirming that hephaestin plays an important role in body iron acquisition, and the similarities of the phenotypes of the whole body and intestine-specific hephalestin knockout mice clarify the important role of hephaESTin specifically in intestinal enterocytes in maintaining whole body iron homeostasis.

Hepcidin: A putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease

  • R. FlemingW. Sly
  • Medicine, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
TLDR
The paper by Nicolas et al. in this issue of PNAS presents the exciting possibility that a central player in the communication of body iron stores to the intestinal absorptive cells may have been identified, the hepatic protein hepcidin.

The ceruloplasmin homolog hephaestin and the control of intestinal iron absorption.

TLDR
Analysis of the sla mouse has supported the model for the regulation of intestinal iron absorption whereby changes in systemic iron requirements alter the levels of basolateral transport components with subsequent regulation of brush border transport.

Intestinal hephaestin potentiates iron absorption in weanling, adult, and pregnant mice under physiological conditions.

TLDR
Results demonstrate that intestinal Heph is essential for optimal iron transport in weanlings and adults of both sexes and during pregnancy, but not in adult mice with iron-deficiency or hemolytic anemia.

Studies on the roles of human ferroportin and hephaestin in iron homeostasis

TLDR
It is suggested that Fpn1 is the major, if not the sole, exporter protein for iron and hephaestin (Hpn), a multicopper ferroxidase in the basolateral membrane of duodenal enterocytes, is intimately involved in iron export from enterocytes into the blood.

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux.

TLDR
An essential physiologic role for ceruloplasmin is revealed in determining the rate of iron efflux from cells with mobilizable iron stores, suggesting that iron accumulation results from altered compartmentalization within the iron cycle.

Physiology of iron transport and the hemochromatosis gene.

  • A. Pietrangelo
  • Biology
    American journal of physiology. Gastrointestinal and liver physiology
  • 2002
TLDR
A model of HFE function in iron metabolism is presented, which is homologous to major histocompatibility complex class I proteins but is not an iron carrier, whereas biochemical and cell biological studies have shown that the transferrin receptor, the main protein devoted to cellular uptake of transferrin iron, interacts with HFE.

Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice.

TLDR
It is suggested that hephaestin, by way of its ferroxidase activity, facilitates iron export from intestinal enterocytes, most likely in cooperation with the basolateral iron transporter, Ireg1.
...

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