Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin

Blood

Volumn 113, Issue 26, 2009, Pages 6707-6715

  Robach, Paul ^a   Recalcati, Stefania ^b   Girelli, Domenico ^c   Gelfi, Cecilia ^d   Aachmann Andersen, Niels J ^e   Thomsen, Jonas J ^e   Norgaard, Anne M ^e   Alberghini, Alessandra ^b   Campostrini, Natascia ^c   Castagna, Annalisa ^c   Viganò, Agnese ^d   Santambrogio, Paolo ^f   Kempf, Tibor ^g   Wollert, Kai C ^g   Moutereau, Stéphane ^h   Lundby, Carsten ^e,i   Cairo, Gaetano ^b  

^a Ecole Nationale de Ski et d'Alpinisme   (France)

^b UNIVERSITY OF MILAN   (Italy)

^c UNIVERSITY OF VERONA   (Italy)

^d UNIVERSITY OF MILAN   (Italy)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

^f SAN RAFFAELE HOSPITAL   (Italy)

^g HANNOVER MEDICAL SCHOOL   (Germany)

^h HENRI MONDOR HOSPITAL   (France)

ⁱ AARHUS UNIVERSITY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

FERRITIN; FERROPORTIN; GROWTH DIFFERENTIATION FACTOR 15; HEPCIDIN; IRON; MYOGLOBIN; OXYGEN; RECOMBINANT ERYTHROPOIETIN; TRANSFERRIN RECEPTOR; ANTIMICROBIAL CATIONIC PEPTIDE; CATION TRANSPORT PROTEIN; CD71 ANTIGEN; HEMOGLOBIN; LEUKOCYTE ANTIGEN; MESSENGER RNA; METAL TRANSPORTING PROTEIN 1;

ADULT; ARTICLE; BLOOD SAMPLING; BONE MARROW; ERYTHROPOIESIS; HUMAN; HUMAN TISSUE; IRON KINETICS; IRON METABOLISM; IRON STORAGE; MALE; MUSCLE; MUSCLE BIOPSY; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN URINE LEVEL; SKELETAL MUSCLE; TREATMENT DURATION; UPREGULATION; URINALYSIS; BIOPSY; BIOSYNTHESIS; CLINICAL TRIAL; CYTOLOGY; DOWN REGULATION; DRUG EFFECT; ERYTHROCYTE VOLUME; GENETICS; HEMATOCRIT; METABOLISM;

ADULT; ANTIGENS, CD; ANTIMICROBIAL CATIONIC PEPTIDES; BIOPSY; CATION TRANSPORT PROTEINS; DOWN-REGULATION; ERYTHROCYTE VOLUME; ERYTHROPOIESIS; ERYTHROPOIETIN, RECOMBINANT; HEMATOCRIT; HEMOGLOBINS; HUMANS; IRON; MALE; MUSCLE, SKELETAL; MYOGLOBIN; RECEPTORS, TRANSFERRIN; RNA, MESSENGER; YOUNG ADULT;

EID: 69249217850     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2008-09-178095     Document Type: Article

References (53)

1. Jelkmann W, Bohlius J, Hallek M, Sytkowski AJ. The erythropoietin receptor in normal and cancer tissues. Crit Rev Oncol Hematol. 2008;67:39-61.
2. Andrews NC. Forging a field: the golden age of iron biology. Blood. 2008;112:219-230.
3. De Domenico I, McVey Ward D, Kaplan J. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol. 2008;9:72-81.
4. Muckenthaler MU. Fine tuning of hepcidin expression by positive and negative regulators. Cell Metab. 2008;8:1-3.
5. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090-2093. (Pubitemid 40007660)
6. Nicolas G, Chauvet C, Viatte L, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110:1037-1044.
7. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101:2461-2463. (Pubitemid 36857598)
8. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. 2007;109:5027-5035. (Pubitemid 46827803)
9. Camberlein E, Zanninelli G, Detivaud L, et al. Anemia in beta-thalassemia patients targets hepatic hepcidin transcript levels independently of iron metabolism genes controlling hepcidin expression. Haematologica. 2008;93:111-115. (Pubitemid 351156158)
10. Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in betathalassemia. Haematologica. 2007;92:583-588. (Pubitemid 350144260)
11. Tanno T, Bhanu NV, Oneal PA, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13:1096-1101. (Pubitemid 47517510)
12. Vokurka M, Krijt J, Sulc K, Necas E. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res. 2006;55:667-674. (Pubitemid 46021227)
13. Lasocki S, Millot S, Andrieu V, et al. Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia. Crit Care Med. 2008;36:2388-2394.
14. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006;108:3730-3735. (Pubitemid 44864551)
15. Nicolas G, Viatte L, Bennoun M, Beaumont C, Kahn A, Vaulont S. Hepcidin, a new iron regulatory peptide. Blood Cells Mol Dis. 2002;29:327-335.
16. Kong WN, Chang YZ, Wang SM, et al. Effect of erythropoietin on hepcidin, DMT1 with IRE, and hephaestin gene expression in duodenum of rats. J Gastroenterol. 2008;43:136-143.
17. Pinto JP, Ribeiro S, Pontes H, et al. Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPalpha. Blood. 2008;111:5727-5733.
18. Fein E, Merle U, Ehehalt R, Herrmann T, Kulaksiz H. Regulation of hepcidin in HepG2 and RINm5F cells. Peptides. 2007;28:951-957. (Pubitemid 46654432)
19. Ordway GA, Garry DJ. Myoglobin: an essential hemoprotein in striated muscle. J Exp Biol. 2004; 207:3441-3446.
20. Robach P, Cairo G, Gelfi C, et al. Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle. Blood. 2007;109:4724-4731. (Pubitemid 46827764)
21. Lundby C, Thomsen JJ, Boushel R, et al. Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume. J Physiol. 2007; 578:309-314. (Pubitemid 44971127)
22. Weiss LG, Clyne N, Divino Fihlho J, Frisenette-Fich C, Kurkus J, Svensson B. The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin beta: results from a randomized controlled multicentre trial. Swedish Study Group. Nephrol Dial Transplant. 2000;15: 2014-2019.
23. Grzeszczak W, Sulowicz W, Rutkowski B, et al. The efficacy and safety of once-weekly and once-fortnightly subcutaneous epoetin beta in peritoneal dialysis patients with chronic renal anaemia. Nephrol Dial Transplant. 2005;20:936-944. (Pubitemid 40704030)
24. Lundby C, Hellsten Y, Jensen MB, Munch AS, Pilegaard H. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle. J Appl Physiol. 2008;104:1154-1160.
25. Burge CM, Skinner SL. Determination of hemoglobin mass and blood volume with CO: evaluation and application of a method. J Appl Physiol. 1995;79:623-631.
26. Gore CJ, Hopkins WG, Burge CM. Errors of measurement for blood volume parameters: a meta-analysis. J Appl Physiol. 2005;99:1745-1758. (Pubitemid 41547171)
27. Kempf T, Horn-Wichmann R, Brabant G, et al. Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem. 2007;53:284-291. (Pubitemid 46338273)
28. Bozzini C, Campostrini N, Trombini P, et al. Measurement of urinary hepcidin levels by SELDITOF-MS in HFE-hemochromatosis. Blood Cells Mol Dis. 2008;40:347-352.
29. Cozzi A, Corsi B, Levi S, Santambrogio P, Biasiotto G, Arosio P. Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin. Blood. 2004; 103:2377-2383. (Pubitemid 38326261)
30. Pietrangelo A, Rocchi E, Ferrari A, Ventura E, Cairo G. Regulation of hepatic transferrin, transferrin receptor and ferritin genes in human siderosis. Hepatology. 1991;14:1083-1089.
31. Lundby C, Achman-Andersen NJ, Thomsen JJ, Norgaard AM, Robach P. Testing for recombinant human erythropoietin in urine: problems associated with current anti-doping testing. J Appl Physiol. 2008;105:417-419.
32. Frazer DM, Wilkins SJ, Becker EM, et al. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology. 2002;123: 835-844.
33. Gehrke SG, Kulaksiz H, Herrmann T, et al. Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron. Blood. 2003;102:371-376. (Pubitemid 36759679)
34. 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. (Pubitemid 47443938)
35. Harrison PM, Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta. 1996;1275: 161-203. (Pubitemid 26248989)
36. Gelfi C, De Palma S, Ripamonti M, et al. New aspects of altitude adaptation in Tibetans: a proteomic approach. FASEB J. 2004;18:612-614.
37. Winder A, Lefkowitz R, Ghoti H, et al. Urinary hepcidin excretion in patients with myelodysplastic syndrome and myelofibrosis. Br J Haematol. 2008;142:669-671. (Pubitemid 352020208)
38. Swinkels DW, Wetzels JF. Hepcidin: a new tool in the management of anaemia in patients with chronic kidney disease? Nephrol Dial Transplant. 2008;23:2450-2453.
39. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011-1023.
40. Nemeth E, Ganz T. Hepcidin and iron-loading anemias. Haematologica. 2006;91:727-732.
41. Chaston T, Chung B, Mascarenhas M, et al. Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells. Gut. 2008; 57:374-382. (Pubitemid 351288105)
42. Zhu BM, McLaughlin SK, Na R, et al. Hematopoietic-specific Stat5-null mice display microcytic hypochromic anemia associated with reduced transferrin receptor gene expression. Blood. 2008;112:2071-2080.
43. Kerenyi MA, Grebien F, Gehart H, et al. Stat 5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1. Blood. 2008;112:3878-3888.
44. Delaby C, Pilard N, Goncalves AS, Beaumont C, Canonne-Hergaux F. Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin. Blood. 2005;106: 3979-3984. (Pubitemid 41739041)
45. Knutson MD, Vafa MR, Haile DJ, Wessling-Resnick M. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood. 2003;102:4191-4197. (Pubitemid 37487007)
46. Abboud S, Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem. 2000;275:19906-19912. (Pubitemid 30441595)
47. Lymboussaki A, Pignatti E, Montosi G, Garuti C, Haile DJ, Pietrangelo A. The role of the iron responsive element in the control of ferroportin1/IREG1/ MTP1 gene expression. J Hepatol. 2003; 39:710-715. (Pubitemid 37372178)
48. Qian ZM, Chang YZ, Leung G, et al. Expression of ferroportin1, hephaestin and ceruloplasmin in rat heart. Biochim Biophys Acta. 2007;1772:527-532. (Pubitemid 46613862)
49. Yang F, Wang X, Haile DJ, Piantadosi CA, Ghio AJ. Iron increases expression of iron-export protein MTP1 in lung cells. Am J Physiol Lung Cell Mol Physiol. 2002;283:L932-L939. (Pubitemid 35204885)
50. De Domenico I, Ward DM, Langelier C, et al. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell. 2007;18: 2569-2578. (Pubitemid 47025722)
51. Robach P, Fulla Y, Westerterp KR, Richalet JP. Comparative response of EPO and soluble transferrin receptor at high altitude. Med Sci Sports Exerc. 2004;36:1493-1498. (Pubitemid 39202616)
52. Mukhopadhyay CK, Mazumder B, Fox PL. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency. J Biol Chem. 2000;275:21048-21054. (Pubitemid 30481794)
53. De Domenico I, Ward DM, di Patti MC, et al. Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin. EMBO J. 2007;26:2823-2831. (Pubitemid 46975784)