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Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Elizabeta Nemeth,1Marie S. Tuttle,2Julie Powelson,2Michael B. Vaughn,2Adriana Donovan,3Diane McVey Ward,2Tomas Ganz,1*Jerry Kaplan2*
Hepcidin is a peptide hormone secreted by the liver in responseto iron loading and inflammation. Decreased hepcidin leads totissue iron overload, whereas hepcidin overproduction leadsto hypoferremia and the anemia of inflammation. Ferroportinis an iron exporter present on the surface of absorptive enterocytes,macrophages, hepatocytes, and placental cells. Here we reportthat hepcidin bound to ferroportin in tissue culture cells.After binding, ferroportin was internalized and degraded, leadingto decreased export of cellular iron. The posttranslationalregulation of ferroportin by hepcidin may thus complete a homeostaticloop: Iron regulates the secretion of hepcidin, which in turncontrols the concentration of ferroportin on the cell surface.
1 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. 2 Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT, USA. 3 Department of Hematology, Children's Hospital, Boston, MA, USA.
* To whom correspondence should be addressed. E-mail: TGanz{at}mednet.ucla.edu (T.G.); jerry.kaplan{at}path.utah.edu (J.K.)
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A. Piperno, D. Girelli, E. Nemeth, P. Trombini, C. Bozzini, E. Poggiali, Y. Phung, T. Ganz, and C. Camaschella (2007)
Blood
110, 4096-4100
|Abstract »|Full Text »|PDF »
Leptin Increases the Expression of the Iron Regulatory Hormone Hepcidin in HuH7 Human Hepatoma Cells.
B. Chung, P. Matak, A. T. McKie, and P. Sharp (2007)
J. Nutr.
137, 2366-2370
|Abstract »|Full Text »|PDF »
Relationship of Hepcidin with Parasitemia and Anemia among Patients with Uncomplicated Plasmodium falciparum Malaria in Ghana.
C. T. Howard, U. S. McKakpo, I. A. Quakyi, K. M. Bosompem, E. A. Addison, K. Sun, D. Sullivan, and R. D. Semba (2007)
Am J Trop Med Hyg
77, 623-626
|Abstract »|Full Text »|PDF »
Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis.
F. B. Sow, W. C. Florence, A. R. Satoskar, L. S. Schlesinger, B. S. Zwilling, and W. P. Lafuse (2007)
J. Leukoc. Biol.
82, 934-945
|Abstract »|Full Text »|PDF »
Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis.
C. Hutchinson, C. A Geissler, J. J Powell, and A. Bomford (2007)
Gut
56, 1291-1295
|Abstract »|Full Text »|PDF »
Elevated iron absorption in the neonatal rat reflects high expression of iron transport genes in the distal alimentary tract.
D. M. Frazer, S. J. Wilkins, and G. J. Anderson (2007)
Am J Physiol Gastrointest Liver Physiol
293, G525-G531
|Abstract »|Full Text »|PDF »
Excess Capacity of the Iron Regulatory Protein System.
W. Wang, X. Di, R. B. D'Agostino Jr., S. V. Torti, and F. M. Torti (2007)
J. Biol. Chem.
282, 24650-24659
|Abstract »|Full Text »|PDF »
Association of diarrhea with anemia among children under age five living in rural areas of Indonesia.
C. T. Howard, S. de Pee, M. Sari, M. W. Bloem, and R. D. Semba (2007)
J Trop Pediatr
53, 238-244
|Abstract »|Full Text »|PDF »
Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry.
A. T. Murphy, D. R. Witcher, P. Luan, and V. J. Wroblewski (2007)
Blood
110, 1048-1054
|Abstract »|Full Text »|PDF »
Sustained Hydrogen Peroxide Induces Iron Uptake by Transferrin Receptor-1 Independent of the Iron Regulatory Protein/Iron-responsive Element Network.
B. Andriopoulos, S. Hegedusch, J. Mangin, H.-D. Riedel, U. Hebling, J. Wang, K. Pantopoulos, and S. Mueller (2007)
J. Biol. Chem.
282, 20301-20308
|Abstract »|Full Text »|PDF »
Systems genetic analysis of peripheral iron parameters in the mouse.
B. C. Jones, J. L. Beard, J. N. Gibson, E. L. Unger, R. P. Allen, K. A. McCarthy, and C. J. Earley (2007)
Am J Physiol Regulatory Integrative Comp Physiol
293, R116-R124
|Abstract »|Full Text »|PDF »
