Clinical Implications of New Insights into Hepcidin-Mediated Regulation of Iron Absorption and Metabolism

Annals of Nutrition and Metabolism

Volumn 71, Issue 3, 2017, Pages 40-48

  Prentice, Andrew M ^a,b  

^a MRC International Nutrition Group   (Gambia)

^b LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

Author keywords

Anemia; Ferroportin; Hepcidin; Iron; Iron deficiency

Indexed keywords

HEPCIDIN; IRON;

ARTICLE; HUMAN; INFECTION; INFLAMMATION; INTESTINE ABSORPTION; IRON ABSORPTION; IRON METABOLISM; METABOLIC REGULATION; NONHUMAN; PRIORITY JOURNAL; ANEMIA; ERYTHROPOIESIS; METABOLISM; PHYSIOLOGY;

ANEMIA; ERYTHROPOIESIS; HEPCIDINS; HUMANS; INFECTION; INFLAMMATION; IRON;

EID: 85038886961     PISSN: 02506807     EISSN: 14219697     Source Type: Journal    
DOI: 10.1159/000480743     Document Type: Article

References (41)

1. Schade AL: Raw hen egg white and the role of iron in growth inhibition of Shigella dysenteriae, Staphylococcus aureus, Escherischia coli and Saccharomyces cerevisiae. Science 1944; 100: 340-341.
2. Schade AL, Caroline L: An iron-binding component in human blood plasma. Science 1946; 104: 340-341.
3. McCance RA, Widdowson EM: Absorption and excretion of iron. Lancet 1937; 230: 680-684.
4. Widdowson EM, McCance RA: Iron exchanges of adults on white and brown bread diets. Lancet 1942; 239: 588-591.
5. Cavell PA, Widdowson EM: Intakes and excretion of iron, copper and zinc in the neonatal period. Arch Dis Child 1964; 39: 496-501.
6. Turnland JR: The use of stable isotopes in mineral nutrition research. J Nutr 1989; 119: 7-14.
7. Kastenmayer P, Davidsson L, Galan P, Cherouvrier F, Hercberg S, Hurrell RF: A double stable isotope technique for measuring iron absorption in infants. Br J Nutr 1994; 71: 411-424.
8. Hunt JR: Iron. Encyclopedia of Human Nutrition, ed 3. Academic Press, 2005, vol 3, pp 82-89.
9. Prentice AM: Iron metabolism, malaria, and other infections: what is all the fuss about? J Nutr 2008; 138: 2537-2541.
10. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA: Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997; 388: 482-488.
11. Wallace DF: The regulation of iron absorption and homeostasis. Clin Biochem Rev 2016; 37: 51-62.
12. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, et al: An ironregulated ferric reductase associated with the absorption of dietary iron. Science 2001; 291: 1755-1759.
13. 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.
14. Osaki S, Johnson DA, Frieden E: The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. J Biol Chem 1966; 241: 2746-2751.
15. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, et al: Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999; 21: 195-199.
16. Hentze MW, Muckenthaler MU, Andrews NC: Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117: 285-297.
17. Ganz T: Systemic iron homeostasis. Physiol Rev 2013; 93: 1721-1741.
18. Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K: LEAP-1, a novel highly disulfidebonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000; 480: 147-150.
19. Park CH, Valore EV, Waring AJ, Ganz T: Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001; 276: 7806-7810.
20. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loréal O: A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001; 276: 7811-7819.
21. 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.
22. Prentice AM, Doherty CP, Abrams SA, Cox SE, Atkinson SH, Verhoef H, Armitage AE, Drakesmith H: Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood 2012; 119: 1922-1928.
23. Drakesmith H, Prentice AM: Hepcidin and the iron-infection axis. Science 2012; 338: 768-72.
24. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T: Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014; 46: 678-684.
25. 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.
26. 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.
27. Ganz T, Nemeth E: Hepcidin and iron homeostasis. Biochim Biophys Acta 2012; 1823: 1434-1443.
28. Goheen MM, Wegmüller R, Bah A, Darboe B, Danso E, Affara M, Gardner D, Patel JC, Prentice AM, Cerami C: Anemia offers stronger protection than sickle cell trait against the erythrocytic stage of falciparum malaria and this protection is reversed by iron supplementation. E Bio Medicine 2016; 14: 123-130.
29. Portugal S, Carret C, Recker M, Armitage AE, Gonçalves LA, Epiphanio S, Sullivan D, Roy C, Newbold CI, Drakesmith H, Mota MM: Host-mediated regulation of superinfection in malaria. Nat Med 2011; 17: 732-737.
30. Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, et al: Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008; 40: 569-571.
31. Atkinson SH, Armitage AE, Khandwala S, Mwangi TW, Uyoga S, Bejon PA, Williams TN, Prentice AM, Drakesmith H: Combinatorial effects of malaria season, iron deficiency, and inflammation determine plasma hepcidin concentration in African children. Blood 2014; 123: 3221-3229.
32. Atkinson SH, Uyoga SM, Armitage AE, Khandwala S, Mugyenyi CK, Bejon P, Marsh K, Beeson JG, Prentice AM, Drakesmith H, Williams TN: Malaria and age variably but critically control hepcidin throughout childhood in Kenya. E Bio Medicine 2015; 2: 1478-1486.
33. Pasricha SR, Atkinson SH, Armitage AE, Khandwala S, Veenemans J, Cox SE, Eddowes LA, Hayes T, Doherty CP, Demir AY, Tijhaar E, Verhoef H, Prentice AM, Drakesmith H: Expression of the iron hormone hepcidin distinguishes different types of anemia in African children. Sci Transl Med 2014; 6: 235re3.
34. Bah A, Pasricha SR, Jallow MW, Sise EA, Wegmuller R, Armitage AE, Drakesmith H, Moore SE, Prentice AM: Serum hepcidin concentrations decline during pregnancy and may identify iron deficiency: analysis of a longitudinal pregnancy cohort in The Gambia. J Nutr 2017; 147: 1131-1137.
35. Wegmüller R, Bah A, Kendall L, Goheen MM, Mulwa S, Cerami C, Moretti D, Prentice AM: Efficacy and safety of hepcidinbased screen-and-treat approaches using two different doses versus a standard universal approach of iron supplementation in young children in rural Gambia: a doubleblind randomised controlled trial. BMC Pediatr 2016; 16: 149.
36. Bah A, Wegmuller R, Cerami C, Kendall L, Pasricha SR, Moore SE, Prentice AM: A double blind randomised controlled trial comparing standard dose of iron supplementation for pregnant women with two screenand-treat approaches using hepcidin as a biomarker for ready and safe to receive iron. BMC Pregnancy Childbirth 2016; 16: 157.
37. Sebastiani G, Wilkinson N, Pantopoulos K: Pharmacological targeting of the hepcidin/ferroportin axis. Front Pharmacol 2016; 7: 160.
38. Preza GC, Ruchala P, Pinon R, Ramos E, Qiao B, Peralta MA, Sharma S, Waring A, Ganz T, Nemeth E: Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest 2011; 121: 4880-4888.
39. Ramos E, Ruchala P, Goodnough JB, Kautz L, Preza GC, Nemeth E, Ganz T: Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis. Blood 2012; 120: 3829-3836.
40. Casu C, Oikonomidou PR, Chen H, Nandi V, Ginzburg Y, Prasad P, Fleming RE, Shah YM, Valore EV, Nemeth E, Ganz T, MacDonald B, Rivella S: Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera. Blood 2016; 128: 265-276.
41. Drakesmith H, Prentice A: Viral infection and iron metabolism. Nat Rev Microbiol 2008; 6: 541-552.