The role of hepcidin in iron metabolism

Acta Haematologica

Volumn 122, Issue 2-3, 2009, Pages 78-86

  Nemeth, Elizabeta ^a,b   Ganz, Tomas ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Anemia of inflammation; Bone morphogenetic protein; Hemochromatosis; Hepcidin; Iron loading anemia

Indexed keywords

ERYTHROPOIETIN; FERROPORTIN; HEPCIDIN; NEUTRALIZING ANTIBODY; PEPTIDE HORMONE ANTAGONIST; SMALL INTERFERING RNA;

ANEMIA; ANEMIA OF INFLAMMATION; CATABOLISM; CHRONIC KIDNEY DISEASE; DRUG MEGADOSE; DRUG STRUCTURE; DRUG SYNTHESIS; HEMOCHROMATOSIS; HUMAN; IRON DEFICIENCY; IRON DEFICIENCY ANEMIA; IRON METABOLISM; IRON METABOLISM DISORDER; IRON OVERLOAD; LIVER ADENOMA; NONHUMAN; PHLEBOTOMY; PRIORITY JOURNAL; REVIEW;

ANTIMICROBIAL CATIONIC PEPTIDES; HOMEOSTASIS; HUMANS; IRON; MODELS, MOLECULAR; PROTEIN CONFORMATION;

EID: 70450214396     PISSN: 00015792     EISSN: None     Source Type: Journal    
DOI: 10.1159/000243791     Document Type: Review

References (25)

1. Valore EV, Ganz T: Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells Mol Dis 2008; 40: 132-138.
2. Peslova G, Petrak J, Kuzelova K, Hrdy I, Halada P, Kuchel PW, Soe-Lin S, Ponka P, Sutak R, Becker E, Huang ML, Suryo RY, Richardson DR, Vyoral D: Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood. Blood 2009; 113: 6225-6236.
3. Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M: Immunoassay for human serum hepcidin. Blood 2008; 112: 4292-4297.
4. Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T: Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood 2005; 106: 2196-2199.
5. Nemeth E, Preza GC, Jung CL, Kaplan J, Waring AJ, Ganz T: The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study. Blood 2006; 107: 328-333.
6. Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M, Sawadogo M, Kahn A, Vaulont S: Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002; 99: 4596-4601.
7. Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC: The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 2005; 1: 191-200.
8. Zhang DL, Hughes RM, Ollivierre-Wilson H, Ghosh MC, Rouault TA: A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression. Cell Metab 2009; 9: 461-473.
9. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J: Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306: 2090-2093.
10. Fernandes A, Preza GC, Phung Y, De Domenico I, Kaplan J, Ganz T, Nemeth E: The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood 2009; 114: 437-443.
11. Wang RH, Li C, Xu X, Zheng Y, Xiao C, Zerfas P, Cooperman S, Eckhaus M, Rouault T, Mishra L, Deng CX: A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab 2005; 2: 399-409.
12. Niederkofler V, Salie R, Arber S: Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest 2005; 115: 2180-2186.
13. Johnson MB, Chen J, Murchison N, Green FA, Enns CA: Transferrin receptor 2: evidence for ligand-induced stabilization and redirection to a recycling pathway. Mol Biol Cell 2007; 18: 743-754.
14. Goswami T, Andrews NC: Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem 2006; 281: 28494-28498.
15. Gao J, Chen J, Kramer M, Tsukamoto H, Zhang AS, Enns CA: Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin- induced hepcidin expression. Cell Metab 2009; 9: 217-227.
16. Lin L, Valore EV, Nemeth E, Goodnough JB, Gabayan V, Ganz T: Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood 2007; 110: 2182-2189.
17. Camaschella C: BMP6 orchestrates iron metabolism. Nat Genet 2009; 41: 386-388.
18. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S: Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006; 108: 3730-3735.
19. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, Moroney JW, Reed CH, Luban NL, Wang RH, Eling TE, Childs R, Ganz T, Leitman SF, Fucharoen S, Miller JL: High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007; 13: 1096-1101.
20. Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, Nizet V, Johnson RS: Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest 2007; 117: 1926-1932.
21. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T: IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004; 113: 1271-1276.
22. Nemeth E, Ganz T: Hepcidin and iron-loading anemias. Haematologica 2006; 91: 727-732.
23. Roy CN, Mak HH, Akpan I, Losyev G, Zurakowski D, Andrews NC: Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood 2007; 109: 4038-4044.
24. Nicolas G, Viatte L, Lou DQ, Bennoun M, Beaumont C, Kahn A, Andrews NC, Vaulont S: Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nat Genet 2003; 34: 97-101.
25. Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, Lin HY, Bloch KD, Peterson RT: Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 2008; 4: 33-41.