Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis.

@article{Parkkila1997AssociationOT,
  title={Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis.},
  author={Seppo Parkkila and Abdul Waheed and Robert S. Britton and Bruce R. Bacon and X. Y. Zhou and Shunji Tomatsu and Robert E. Fleming and William S. Sly},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={1997},
  volume={94 24},
  pages={
          13198-202
        }
}
  • S. Parkkila, A. Waheed, +5 authors W. Sly
  • Published 25 November 1997
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
Hereditary hemochromatosis (HH) is a common autosomal recessive disease associated with loss of regulation of dietary iron absorption and excessive iron deposition in major organs of the body. Recently, a candidate gene for HH (also called HFE) was identified that encodes a novel MHC class I-like protein. Most patients with HH are homozygous for the same mutation in the HFE gene, resulting in a C282Y change in the HFE protein. Studies in cultured cells show that the C282Y mutation abrogates the… Expand
Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum.
  • A. Waheed, S. Parkkila, +6 authors W. Sly
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
It is proposed that the HFE protein modulates the uptake of transferrin-bound iron from plasma by crypt enterocyte and participates in the mechanism by which the crypt enterocytes sense the level of body iron stores. Expand
Expression of the Hereditary Hemochromatosis Protein HFE Increases Ferritin Levels by Inhibiting Iron Export in HT29 Cells*
TLDR
A role for HFE in inhibition of iron efflux in HT29 cells is pointed to, a distinct role from that in HeLa and human embryonic kidney 293 cells where HFE has been shown to inhibit TF-mediated iron uptake resulting in decreased ferritin levels. Expand
HFE gene knockout produces mouse model of hereditary hemochromatosis.
  • X. Zhou, S. Tomatsu, +12 authors W. Sly
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1998
TLDR
The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload. Expand
Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis
  • A. Waheed, J. Grubb, +6 authors W. Sly
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
It is proposed that Chinese hamster ovary cells provide a model to explain the effect of the HFE-β2M complex in duodenal crypt cells, which appears to facilitate the uptake of transferrin-bound iron to sense the level of body iron stores. Expand
Possible roles of the hereditary hemochromatosis protein, HFE, in regulating cellular iron homeostasis.
  • C. Enns
  • Chemistry, Medicine
  • Biological research
  • 2006
TLDR
The background and a model as to possible mechanisms of how HFE could exert different effects on iron homeostasis in different cell types are given. Expand
Immunohistochemistry of the Hfe protein in patients with hereditary hemochromatosis, iron deficiency anemia, and normal controls.
TLDR
Hfe is expressed strongly in the deep crypts of the small intestine of normal subjects and is not regulated by therapeutic iron depletion in patients with hemochromatosis who are homozygous for the C282Y mutation. Expand
The haemochromatosis protein HFE induces an apparent iron-deficient phenotype in H1299 cells that is not corrected by co-expression of beta 2-microglobulin.
TLDR
Clones of human H1299 lung cancer cells that express wild-type, C282Y or H63D HFE under the control of a tetracycline-inducible promoter suggest that the apparent iron-deficient phenotype elicited by HFE is not linked to beta(2)M insufficiency. Expand
Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1.
  • R. Fleming, M. C. Migas, +7 authors W. Sly
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
The hypothesis that HFE-/- mice have increased duodenal expression of the divalent metal transporter (DMT1) is tested and support the model for HH in which HFE mutations lead to inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE) mRNA, up-regulation of DFT, and increased absorption of dietary iron. Expand
Pumping iron: the strange partnership of the hemochromatosis protein, a class I MHC homolog, with the transferrin receptor
  • C. Enns
  • Biology, Medicine
  • Traffic
  • 2001
TLDR
The mechanism whereby a class I MHC homolog modifies the function of a membrane receptor and how this dynamic complex of molecules regulates iron transport across intestinal epithelial cells is the subject of this review. Expand
Overexpression of hemochromatosis protein, HFE, alters transferrin recycling process in human hepatoma cells.
TLDR
The results strongly suggest an additional role of HFE on transferrin receptor recycling in addition to the decrease of receptor affinity, resulting in the reduced cellular iron. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 23 REFERENCES
Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract.
  • S. Parkkila, A. Waheed, +5 authors W. Sly
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
It is shown that the HLA-H protein not only varies in its pattern of expression along the cranial/caudal axis of the gastrointestinal tract but that it has a unique subcellular localization in the crypts of the small intestine in proximity to the presumed sites of iron absorption. Expand
The Hemochromatosis Founder Mutation in HLA-H Disrupts β2-Microglobulin Interaction and Cell Surface Expression*
TLDR
The first functional significance of the C282Y mutation is described by suggesting that an abnormality in protein trafficking and/or cell-surface expression of HLA-H leads to HH disease. Expand
Mutation analysis of the HLA-H gene in Italian hemochromatosis patients.
TLDR
It is reported that the Cys282Tyr change accounts for 69% of HH chromosomes in a series of 75 unrelated Italian patients who fulfilled well-defined criteria for HH diagnosis, suggesting that in Italy the disease is more heterogeneous than reported in northern Europe. Expand
A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis
TLDR
Using linkage–disequilibrium and full haplotype analysis, a region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical–by–descent in 85% of patient chromosomes is identified, containing a gene related to the MHC class I family, termed HLA–H, containing two missense alterations. Expand
Mutations in the MHC class I-like candidate gene for hemochromatosis in French patients
TLDR
The detection of 845A homozygosity should now permit diagnosis of a readily curable disease and the prevention of sometimes deadly complications in at least 72% of the patients. Expand
Haemochromatosis and HLA–H
TLDR
Some of the uncertainty surrounding the role of HLA-H in HH may be resolved by the identification of complete concordance of the C282Y mutation (or some other mutation) in HLA H with disease status in HH families. Expand
Mutation analysis in hereditary hemochromatosis.
TLDR
The DNA of 147 patients of European origin clinically diagnosed with idiopathic hemochromatosis and 193 controls was examined for mutations of the HLA-H gene at nt 845 and nt 187, suggesting the presence of as yet undiscovered mutations existing in trans with 845A and in linkage disequilibrium with 187G. Expand
Perinatal hemochromatosis. Clinical, morphologic, and quantitative iron studies.
TLDR
Liver morphology, including immunocytochemistry and ultrastructure, was similar in the 5 infants and suggested that liver disease commenced as massive necrosis in midfetal life, and hepatic iron overload was directly involved in pathogenesis. Expand
An IgG‐transporting Fc receptor expressed in the syncytiotrophoblast of human placenta
TLDR
A transport model is proposed in which maternal IgG binds FcRn at low pH in endosomes within the syncytiotrophoblast, and this corresponds with the pH dependence of IgG binding to F cRn and is consistent with the presence of Fc Rn in syncyTiotrophicoblast. Expand
The role of transferrin and ferritin in the fetal-maternal-placental unit.
TLDR
Ferritin was shown to be present in all layers of the trophoblast and especially in the Syncytiotrophoblast, and transferrin was localized on the site facing the intervillous space, on the surface of the microvilli of the syncyTiotrophoblasts. Expand
...
1
2
3
...