Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice

PLoS ONE

Volumn 8, Issue 3, 2013, Pages

  Matak, Pavle ^a,b,c,h   Zumerle, Sara ^a,b,c   Mastrogiannaki, Maria ^a,b,c   El Balkhi, Souleiman ^d   Delga, Stephanie ^a,b,c   Mathieu, Jacques R R ^a,b,c   Canonne Hergaux, François ^b,e,f   Poupon, Joel ^d   Sharp, Paul A ^g   Vaulont, Sophie ^a,b,c   Peyssonnaux, Carole ^a,b,c  

^a INSTITUT COCHIN   (France)

^b CNRS   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d HÔPITAL LARIBOISIÈRE   (France)

^e France   (France)

^f UNIVERSITÉ PAUL SABATIER   (France)

^g KING'S COLLEGE LONDON   (United Kingdom)

^h DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FERROPORTIN; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR 2ALPHA;

ANEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; COPPER DEFICIENCY; CYBRD1 GENE; DISEASE COURSE; DOWN REGULATION; DUODENAL HYPOXIA; DUODENUM DISEASE; FEMALE; GENE; GENE TARGETING; HYPOXIA; IRON ABSORPTION; IRON TRANSPORT; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; SLC11A2 GENE; SLC40A1 GENE; UPREGULATION;

ABSORPTION; ANEMIA; ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL HYPOXIA; COPPER; DOWN-REGULATION; DUODENUM; FEMALE; INJECTIONS, INTRAPERITONEAL; IRON; MALE; MICE; MICE, INBRED C57BL; UP-REGULATION;

MUS;

EID: 84875495756     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0059538     Document Type: Article

References (48)

1. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, et al. (2001) An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291: 1755-1759.
2. Ohgami RS, Campagna DR, McDonald A, Fleming MD, (2006) The Steap proteins are metalloreductases. Blood 108: 1388-1394.
3. Wyman S, Simpson RJ, McKie AT, Sharp PA, (2008) Dcytb (Cybrd1) functions as both a ferric and a cupric reductase in vitro. FEBS Letters 582: 1901-1906.
4. Collins JF, Prohaska JR, Knutson MD, (2010) Metabolic crossroads of iron and copper. Nutr Rev 68: 133-147.
5. Semenza GL, (2009) Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 24: 97-106.
6. Shah YM, Matsubara T, Ito S, Yim S-H, Gonzalez FJ, (2009) Intestinal Hypoxia-Inducible Transcription Factors Are Essential for Iron Absorption following Iron Deficiency. Cell Metabolism 9: 152-164.
7. Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, et al. (2009) HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. J Clin Invest 119: 1159-1166.
8. Taylor M, Qu A, Anderson ER, Matsubara T, Martin A, et al. (2011) Hypoxia-inducible factor-2alpha mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice. Gastroenterology 140: 2044-2055.
9. Anderson SA, Nizzi CP, Chang YI, Deck KM, Schmidt PJ, et al. (2013) The IRP1-HIF-2alpha Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption. Cell Metab 17: 282-290.
10. Hentze MW, Muckenthaler MU, Galy B, Camaschella C, (2010) Two to tango: regulation of Mammalian iron metabolism. Cell 142: 24-38.
11. Ganz T, (2011) Hepcidin and iron regulation, 10 years later. Blood 117: 4425-4433.
12. Chung B, Chaston T, Marks J, Srai SK, Sharp PA, (2009) Hepcidin decreases iron transporter expression in vivo in mouse duodenum and spleen and in vitro in THP-1 macrophages and intestinal Caco-2 cells. J Nutr 139: 1457-1462.
13. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, et al. (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306: 2090-2093.
14. Kim BE, Turski ML, Nose Y, Casad M, Rockman HA, et al. (2010) Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs. Cell Metab 11: 353-363.
15. Fox PL, (2003) The copper-iron chronicles: the story of an intimate relationship. Biometals 16: 9-40.
16. Nittis T, Gitlin JD, (2004) Role of copper in the proteosome-mediated degradation of the multicopper oxidase hephaestin. J Biol Chem 279: 25696-25702.
17. Owen CA Jr, (1973) Effects of iron on copper metabolism and copper on iron metabolism in rats. Am J Physiol 224: 514-518.
18. Reeves PG, DeMars LC, (2004) Copper deficiency reduces iron absorption and biological half-life in male rats. J Nutr 134: 1953-1957.
19. Williams DM, Loukopoulos D, Lee GR, Cartwright GE, (1976) Role of copper in mitochondrial iron metabolism. Blood 48: 77-85.
20. Martin F, Linden T, Katschinski DM, Oehme F, Flamme I, et al. (2005) Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation. Blood 105: 4613-4619.
21. Hait-Darshan R, Babushkin T, Malik Z, (2009) Regulation of heme synthesis and proteasomal activity by copper: possible implications for Wilson's disease. J Environ Pathol Toxicol Oncol 28: 209-221.
22. Harada M, Miyagawa K, Honma Y, Hiura M, Shibata M, et al. (2011) Excess copper chelating therapy for Wilson disease induces anemia and liver dysfunction. Internal medicine 50: 1461-1464.
23. Merle U, Tuma S, Herrmann T, Muntean V, Volkmann M, et al. (2010) Evidence for a critical role of ceruloplasmin oxidase activity in iron metabolism of Wilson disease gene knockout mice. J Gastroenterol Hepatol 25: 1144-1150.
24. Nittis T, Gitlin JD, (2002) The copper-iron connection: hereditary aceruloplasminemia. Semin Hematol 39: 282-289.
25. Prella M, Baccala R, Horisberger JD, Belin D, Di Raimondo F, et al. (2001) Haemolytic onset of Wilson disease in a patient with homozygous truncation of ATP7B at Arg1319. British journal of haematology 114: 230-232.
26. Chen H, Huang G, Su T, Gao H, Attieh ZK, et al. (2006) Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency. J Nutr 136: 1236-1241.
27. Anderson ER, Xue X, Shah YM, (2011) Intestinal hypoxia-inducible factor-2alpha (HIF-2alpha) is critical for efficient erythropoiesis. The Journal of biological chemistry 286: 19533-19540.
28. Sato Y, Endo H, Okuyama H, Takeda T, Iwahashi H, et al. (2011) Cellular hypoxia of pancreatic beta-cells due to high levels of oxygen consumption for insulin secretion in vitro. J Biol Chem 286: 12524-12532.
29. Nose Y, Kim BE, Thiele DJ, (2006) Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. Cell Metab 4: 235-244.
30. Andrews NC, Faller DV, (1991) A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res 19: 2499.
31. Canonne-Hergaux F, Donovan A, Delaby C, Wang HJ, Gros P, (2006) Comparative studies of duodenal and macrophage ferroportin proteins. Am J Physiol Gastrointest Liver Physiol 290: G156-163.
32. Canonne-Hergaux F, Gruenheid S, Ponka P, Gros P, (1999) Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93: 4406-4417.
33. Latunde-Dada GO, Xiang L, Simpson RJ, McKie AT (2011) Duodenal cytochrome b (Cybrd 1) and HIF-2alpha expression during acute hypoxic exposure in mice. Eur J Nutr.
34. Jiang Y, Reynolds C, Xiao C, Feng W, Zhou Z, et al. (2007) Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. J Exp Med 204: 657-666.
35. Feng W, Ye F, Xue W, Zhou Z, Kang YJ, (2009) Copper regulation of hypoxia-inducible factor-1 activity. Mol Pharmacol 75: 174-182.
36. Sanchez M, Galy B, Muckenthaler MU, Hentze MW, (2007) Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency. Nat StructMol Biol 14: 420-426.
37. Auclair S, Feillet-Coudray C, Coudray C, Schneider S, Muckenthaler MU, et al. (2006) Mild copper deficiency alters gene expression of proteins involved in iron metabolism. Blood Cells Mol Dis 36: 15-20.
38. Hansen SL, Trakooljul N, Liu HC, Hicks JA, Ashwell MS, et al. (2010) Proteins involved in iron metabolism in beef cattle are affected by copper deficiency in combination with high dietary manganese, but not by copper deficiency alone. J Anim Sci 88: 275-283.
39. Prohaska JR, Broderius M, (2012) Copper deficiency has minimal impact on ferroportin expression or function. Biometals 25: 633-642.
40. Chen H, Su T, Attieh ZK, Fox TC, McKie AT, et al. (2003) Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency. Blood 102: 1893-1899.
41. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, et al. (1999) Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. NatGenet 21: 195-199.
42. Cherukuri S, Potla R, Sarkar J, Nurko S, Harris ZL, et al. (2005) Unexpected role of ceruloplasmin in intestinal iron absorption. Cell Metab 2: 309-319.
43. Ranganathan PN, Lu Y, Fuqua BK, Collins JF, (2012) Discovery of a cytosolic/soluble ferroxidase in rodent enterocytes. Proc Natl Acad Sci U S A 109: 3564-3569.
44. Pyatskowit JW, Prohaska JR, (2008) Iron injection restores brain iron and hemoglobin deficits in perinatal copper-deficient rats. J Nutr 138: 1880-1886.
45. Pyatskowit JW, Prohaska JR, (2008) Copper deficient rats and mice both develop anemia but only rats have lower plasma and brain iron levels. Comp Biochem Physiol C Toxicol Pharmacol 147: 316-323.
46. Reeves PG, Demars LC, (2005) Repletion of copper-deficient rats with dietary copper restores duodenal hephaestin protein and iron absorption. Exp Biol Med (Maywood) 230: 320-325.
47. Schneider BD, Leibold EA, (2003) Effects of iron regulatory protein regulation on iron homeostasis during hypoxia. Blood 102: 3404-3411.
48. Sharp P, (2004) The molecular basis of copper and iron interactions. Proc Nutr Soc 63: 563-569.