New developments in the regulation of intestinal copper absorptionn

Nutrition Reviews

Volumn 67, Issue 11, 2009, Pages 658-672

  Van Den Berghe, Peter V E ^a   Klomp, Leo W J ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

ATP7A; Copper; HCTR1; Homeostasis; Intestine

Indexed keywords

CARRIER PROTEIN; COPPER; HISTIDINE; PENICILLAMINE; TETRATHIOMOLYBDATE AMMONIUM; TRIENTINE; ZINC; CERULOPLASMIN; METALLOTHIONEIN; TRACE ELEMENT;

COPPER METABOLISM; DIETARY INTAKE; ENZYME ACTIVITY; EXCRETION; HUMAN; INTESTINE ABSORPTION; INTESTINE CELL; MENKES SYNDROME; NONHUMAN; OXIDATION REDUCTION REACTION; PORTAL VEIN BLOOD FLOW; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; WILSON DISEASE; DRUG EFFECT; GENETICS; HOMEOSTASIS; METABOLISM; PHYSIOLOGY; TRANSPORT AT THE CELLULAR LEVEL;

BIOLOGICAL TRANSPORT; CERULOPLASMIN; COPPER; ENTEROCYTES; HEPATOLENTICULAR DEGENERATION; HOMEOSTASIS; HUMANS; INTESTINAL ABSORPTION; MENKES KINKY HAIR SYNDROME; METALLOTHIONEIN; OXIDATION-REDUCTION; TRACE ELEMENTS;

EID: 74949100486     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1111/j.1753-4887.2009.00250.x     Document Type: Review

References (135)

1. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12:1161-1208.
2. Linder MC, Hazegh-Azam M. Copper biochemistry and molecular biology. Am J Clin Nutr. 1996;63(Suppl):S797-S811.
3. Lewis KO. The nature and excretion of biliary copper in man. Clin Sci. 1973;45:133-134.
4. Lewis KO. The nature of the copper complexes in bile and their relationship to the absorption and excretion of copper in normal subjects and in Wilson's disease. Gut. 1973;14:221-232.
5. Araya M, Kelleher SL, Arredondo MA, et al. Effects of chronic copper exposure during early life in rhesus monkeys. Am J Clin Nutr. 2005;81:1065-1071. (Pubitemid 41724947)
6. August D, Janghorbani M, Young VR. Determination of zinc and copper absorption at three dietary Zn-Cu ratios by using stable isotope methods in young adult and elderly subjects. Am J Clin Nutr. 1989;50:1457-1463.
7. Hunt JR, Vanderpool RA. Apparent copper absorption froma vegetarian diet. Am J Clin Nutr. 2001;74:803-807.
8. Johnson PE, Milne DB, Lykken GI. Effects of age and sex on copper absorption, biological half-life, and status in humans. Am J Clin Nutr. 1992;56:917-925.
9. Olivares M, Lonnerdal B, Abrams SA, Pizarro F, Uauy R. Age and copper intake do not affect copper absorption, measured with the use of 65Cu as a tracer, in young infants. Am J Clin Nutr. 2002;76:641-645.
10. Turnlund JR. Human whole-body copper metabolism. Am J Clin Nutr. 1998;67(Suppl):S960-S964.
11. Turnlund JR, Keyes WR, Anderson HL, Acord LL. Copper absorption and retention in young men at three levels of dietary copper by use of the stable isotope 65Cu. Am J Clin Nutr. 1989;49:870-878.
12. Turnlund JR, King JC, Gong B, Keyes WR,Michel MC. A stable isotope study of copper absorption in young men: effect of phytate and alpha-cellulose. Am J Clin Nutr. 1985;42:18-23.
13. Turnlund JR, Swanson CA, King JC. Copper absorption and retention in pregnantwomen fed diets based on animal and plant proteins. J Nutr. 1983;113:2346-2352.
14. Wapnir RA. Copper absorption and bioavailability. Am J Clin Nutr. 1998;67(Suppl):S1054-S1060.
15. Varada KR, Harper RG, Wapnir RA. Development of copper intestinal absorption in the rat. Biochem Med Metab Biol. 1993;50:277-283.
16. Bronner F, Yost JH. Saturable and nonsaturable copper and calcium transport in mouse duodenum. Am J Physiol. 1985;249:G108-G112.
17. Bronner F. Recent developments in intestinal calcium absorption. Nutr Rev. 2009;67:109-113.
18. Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998; 1:85-98.
19. Mercer JF. Menkes syndrome and animal models. Am J Clin Nutr. 1998;67(Suppl):S1022-S1028.
20. Tumer Z, Horn N. Menkes disease: underlying genetic defect and new diagnostic possibilities. J Inherit Metab Dis. 1998;21:604-612.
21. Nose Y, Kim BE, Thiele DJ. Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. Cell Metab. 2006;4:235-244.
22. Bauerly KA, Kelleher SL, Lönnerdal B. Functional and molecular responses of suckling rat pups and human intestinal Caco-2 cells to copper treatment. J Nutr Biochem. 2004; 15:155-162.
23. Bauerly KA, Kelleher SL, Lönnerdal B. Effects of copper supplementation on copper absorption, tissue distribution, and copper transporter expression in an infant rat model. Am J Physiol Gastrointest Liver Physiol. 2005;288:G1007-G1014.
24. Moriya M, Ho YH, Grana A, et al. Copper is taken up efficiently from albumin and alpha-2-macroglobulin by cultured human cells by more than one mechanism. Am J Physiol Cell Physiol. 2008;295(3):C708-721.
25. Hellman NE, Gitlin JD. Ceruloplasmin metabolism and function. Annu Rev Nutr. 2002;22:439-458.
26. BarrowL, Tanner MS. Copper distribution among serum proteins in paediatric liver disorders and malignancies. Eur J Clin Invest. 1988;18:555-560.
27. Wirth PL, Linder MC. Distribution of copper among components of human serum. J Natl Cancer Inst. 1985; 75:277-284.
28. Harris ZL, Klomp LW, Gitlin JD. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am J Clin Nutr. 1998;67(Suppl):S972-S977.
29. Meyer LA, Durley AP, Prohaska JR, Harris ZL. Copper transport and metabolism are normal in aceruloplasminemic mice. J Biol Chem. 2001;276:36857-36861.
30. Omoto E, Tavassoli M. The role of endosomal traffic in the transendothelial transport of ceruloplasmin in the liver. Biochem Biophys Res Commun. 1989;162:1346-1350.
31. Omoto E, Tavassoli M. Purification and characterization of ceruloplasmin receptors. Trans Assoc Am Physicians. 1989;102:170-175.
32. Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson's disease. Lancet. 2007;369:397-408.
33. Kenney SM, Cox DW. Sequence variation database for Wilson disease copper transporter ATP7B. Hum Mutat. 2007;28(12):1171-1177.
34. Hardman B, Michalczyk A, Greenough M, Camakaris J, Mercer J, Ackland L. Distinct functional roles for the Menkes and Wilson copper translocating P-type ATPases in human placental cells. Cell Physiol Biochem. 2007;20:1073-1084.
35. Kuo YM, Gitschier J, Packman S. Developmental expression of the mouse mottled and toxic milk genes suggests distinct functions for the Menkes and Wilson disease copper transporters. Hum Mol Genet. 1997;6:1043-1049.
36. Michalczyk A, Bastow E, Greenough M, et al. ATP7B expression in human breast epithelial cells is mediated by lactational hormones. J Histochem Cytochem. 2008;56:389-399.
37. Walshe JM. Wilson's disease; new oral therapy. Lancet. 1956;270:25-26.
38. Brewer GJ, Dick RD, Johnson V, et al. Treatment of Wilson's disease with ammonium tetrathiomolybdate. I. Initial therapy in 17 neurologically affected patients. Arch Neurol. 1994;51:545-554.
39. Brewer GJ, Dick RD, Yuzbasiyan-Gurkin V, Tankanow R, Young AB, Kluin KJ. Initial therapy of patients with Wilson's disease with tetrathiomolybdate. Arch Neurol. 1991;48:42-47.
40. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V. Treatment of Wilson's disease with zinc. IX: response of serum lipids. J Lab Clin Med. 1991;118:466-470.
41. Danks DM. Disorders of copper transport. In: Scriver CR, Beaudet AL, Sly WM, Valle D, eds. The Metabolic and Molecular Basis of Inherited Disease. New York: McGraw-Hill; 1995:2211-2235.
42. Gu YH, Kodama H, Shiga K, Nakata S, Yanagawa Y, Ozawa H. A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis. J Inherit Metab Dis. 2005;28:473-478.
43. Tonnesen T, KleijerWJ, Horn N. Incidence ofMenkes disease. Hum Genet. 1991;86:408-410.
44. Danks DM. The mild form of Menkes disease: progress report on the original case. Am J Med Genet. 1988;30:859-864.
45. Kaler SG, Gallo LK, Proud VK, et al. Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet. 1994;8:195-202.
46. Procopis P, Camakaris J, Danks DM. A mild form of Menkes steely hair syndrome. J Pediatr. 1981;98:97-99.
47. La Fontaine SL, Firth SD, Camakaris J, et al. Correction of the copper transport defect of Menkes patient fibroblasts by expression of the Menkes andWilson ATPases. J Biol Chem. 1998;273:31375-31380.
48. Sarkar B, Lingertat-Walsh K, Clarke JT. Copper-histidine therapy for Menkes disease. J Pediatr. 1993;123:828-830.
49. Nittis T, Gitlin JD. Role of copper in the proteosomemediated degradation of the multicopper oxidase hephaestin. J Biol Chem. 2004;279:25696-25702.
50. Vulpe CD, Kuo YM, Murphy TL, et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet. 1999;21:195-199.
51. Dancis A, Yuan DS, Haile D, et al. Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport. Cell. 1994;76:393-402.
52. Kampfenkel K, Kushnir S, Babiychuk E, Inze D, Van Montagu M. Molecular characterization of a putative Arabidopsis thaliana copper transporter and its yeast homologue. J Biol Chem. 1995;270:28479-28486.
53. Knight SA, Labbe S, Kwon LF, Kosman DJ, Thiele DJ. A widespread transposable element masks expression of a yeast copper transport gene. Genes Dev. 1996;10:1917-1929.
54. Kuo YM, Zhou B, Cosco D, Gitschier J. The copper transporter CTR1 provides an essential function in mammalian embryonic development. Proc Natl Acad Sci USA. 2001;98:6836-6841.
55. Lee J, Prohaska JR, Thiele DJ. Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development. Proc Natl Acad Sci USA. 2001;98:6842-6847.
56. Yuan DS, Stearman R, Dancis A, Dunn T, Beeler T, Klausner RD. The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake. Proc Natl Acad Sci USA. 1995;92:2632-2636.
57. Nyasae L, Bustos R, Braiterman L, Eipper B, Hubbard A. Dynamics of endogenous ATP7A (Menkes protein) in intestinal epithelial cells: copper-dependent redistribution between two intracellular sites. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1181-G1194.
58. Hamza I, Schaefer M, Klomp LW, Gitlin JD. Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis. Proc Natl Acad Sci USA. 1999;96:13363-13368.
59. Larin D, Mekios C, Das K, Ross B, Yang AS, Gilliam TC. Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p. J Biol Chem. 1999;274:28497-28504.
60. Portnoy ME, Rosenzweig AC, Rae T, Huffman DL, O'Halloran TV, Culotta VC. Structure-function analyses of the ATX1 metallochaperone. J Biol Chem. 1999;274:15041-15045.
61. Hamza I, Prohaska J, Gitlin JD. Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. Proc Natl Acad Sci USA. 2003;100:1215-1220.
62. Turski ML, Thiele DJ. Drosophila Ctr1A functions as a copper transporter essential for development. J Biol Chem. 2007;282:24017-24026.
63. Zhou H, Cadigan KM, Thiele DJ. A copper-regulated transporter required for copper acquisition, pigmentation, and specific stages of development in Drosophila melanogaster. J Biol Chem. 2003;278:48210-48218.
64. Arredondo M, Muñoz P, Mura CV, Nùñez MT. DMT1, a physiologically relevant apical Cu1+ transporter of intestinal cells. Am J Physiol Cell Physiol. 2003;284:C1525-C1530.
65. Southon A, Farlow A, Norgate M, Burke R, Camakaris J. Malvolio is a copper transporter in Drosophila melanogaster. J Exp Biol. 2008;211:709-716.
66. Bertinato J, Swist E, Plouffe LJ, Brooks SP, L'Abbe MR. Ctr2 is partially localized to the plasma membrane and stimulates copper uptake in COS-7 cells. Biochem J. 2008;409:731-740.
67. van den Berghe PV, Folmer DE, Malingré HE, et al. Human copper transporter 2 is localized in late endosomes and lysosomes and facilitates cellular copper uptake. Biochem J. 2007;407:49-59.
68. Abdel-Ghany SE, Muller-Moule P, Niyogi KK, Pilon M, Shikanai T. Two P-type ATPases are required for copper delivery in Arabidopsis thaliana chloroplasts. Plant Cell. 2005;17:1233-1251.
69. Mendelsohn BA, Yin C, Johnson SL, Wilm TP, Solnica-Krezel L, Gitlin JD. Atp7a determines a hierarchy of copper metabolism essential for notochord development. Cell Metab. 2006;4:155-162.
70. Arguello JM, Eren E, Gonzalez-GuerreroM. The structure and function of heavy metal transport P1B-ATPases. Biometals. 2007;20:233-248.
71. Lutsenko S, LeShane ES, Shinde U. Biochemical basis of regulation of human copper-transporting ATPases. Arch Biochem Biophys. 2007;463:134-148. (Pubitemid 47030341)
72. Paynter JA, Grimes A, Lockhart P, Mercer JF. Expression of the Menkes gene homologue in mouse tissues lack of effect of copper on the mRNA levels. FEBS Lett. 1994;351:186-190.
73. Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet. 1993;3:7-13.
74. Kelleher SL, Lönnerdal B. Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization. Am J Physiol Regul Integr Comp Physiol. 2006;291:R1181-R1191.
75. Petris MJ, Mercer JF, Culvenor JG, Lockhart P, Gleeson PA, Camakaris J. Ligand-regulated transport of the Menkes copper P-type ATPase efflux pump fromthe Golgi apparatus to the plasma membrane: a novel mechanism of regulated trafficking. EMBO J. 1996;15:6084-6095.
76. Setty SR, Tenza D, Sviderskaya EV, Bennett DC, Raposo G, Marks MS. Cell-specific ATP7A transport sustains copperdependent tyrosinase activity in melanosomes. Nature. 2008;454:1142-1146.
77. Yamaguchi Y, Heiny ME, Suzuki M, Gitlin JD. Biochemical characterization and intracellular localization of the Menkes disease protein. Proc Natl Acad Sci USA. 1996;93:14030-14035.
78. Francis MJ, Jones EE, Levy ER, Martin RL, Ponnambalam S, Monaco AP. Identification of a di-leucine motif within the C terminus domain of the Menkes disease protein that mediates endocytosis from the plasma membrane. J Cell Sci. 1999;112:1721-1732.
79. Petris MJ, Smith K, Lee J, Thiele DJ. Copper-stimulated endocytosis and degradation of the human copper transporter, hCtr1. J Biol Chem. 2003;278:9639-9646.
80. Ravia JJ, Stephen RM, Ghishan FK, Collins JF. Menkes copper ATPase (Atp7a) is a novel metal-responsive gene in rat duodenum, and immunoreactive protein is present on brush-border and basolateral membrane domains. J Biol Chem. 2005;280:36221-36227.
81. Monty JF, Llanos RM, Mercer JF, Kramer DR. Copper exposure induces trafficking of the menkes protein in intestinal epithelium of ATP7A transgenic mice. J Nutr. 2005; 135:2762-2766.
82. Nose Y, Rees EM, Thiele DJ. Structure of the Ctr1 copper trans'PORE'ter reveals novel architecture. Trends Biochem Sci. 2006;31:604-607.
83. Rae TD, Schmidt PJ, Pufahl RA, Culotta VC, O'Halloran TV. Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. Science. 1999;284:805-808.
84. Prohaska JR, Gybina AA. Intracellular copper transport in mammals. J Nutr. 2004;134:1003-1006.
85. O'Halloran TV, Culotta VC. Metallochaperones, an intracellular shuttle service for metal ions. J Biol Chem. 2000;275:25057-25060.
86. Arnesano F, Banci L, Bertini I, et al. Characterization of the binding interface between the copper chaperone Atx1 and the first cytosolic domain of Ccc2 ATPase. J Biol Chem. 2001;276:41365-41376.
87. Pufahl RA, Singer CP, Peariso KL, et al. Metal ion chaperone function of the soluble Cu(I) receptor Atx1. Science. 1997;278:853-856.
88. Strausak D, Howie MK, Firth SD, et al. Kinetic analysis of the interaction of the copper chaperone Atox1 with the metal binding sites of the Menkes protein. J Biol Chem. 2003;278:20821-20827.
89. van Dongen EM, Klomp LW, Merkx M. Copper-dependent protein-protein interactions studied by yeast two-hybrid analysis. Biochem Biophys Res Commun. 2004;323:789-795.
90. Arguello JM, Gonzalez-Guerrero M. Cu+-ATPases brake system. Structure. 2008;16:833-834.
91. Hamza I, Faisst A, Prohaska J, Chen J, Gruss P, Gitlin JD. The metallochaperone Atox1 plays a critical role in perinatal copper homeostasis. Proc Natl Acad Sci USA. 2001;98:6848-6852.
92. Gonzalez-Guerrero M, Arguello JM. Mechanism of Cu+- transporting ATPases: soluble Cu+ chaperones directly transfer Cu+ to transmembrane transport sites. Proc Natl Acad Sci USA. 2008;105:5992-5997.
93. Gonzalez-Guerrero M, Eren E, Rawat S, Stemmler TL, Arguello JM. Structure of the two transmembrane Cu+ transport sites of the Cu+-ATPases. J Biol Chem. 2008; 283:29753-29759.
94. Zhou B, Gitschier J. hCTR1: a human gene for copper uptake identified by complementation in yeast. Proc Natl Acad Sci USA. 1997;94:7481-7486.
95. Eisses JF, Kaplan JH. Molecular characterization of hCTR1, the human copper uptake protein. J Biol Chem. 2002; 277:29162-29171.
96. Lee J, Peña MM, Nose Y, Thiele DJ. Biochemical characterization of the human copper transporter Ctr1. J Biol Chem. 2002;277:4380-4387.
97. Haremaki T, Fraser ST, Kuo YM, Baron MH, Weinstein DC. Vertebrate Ctr1 coordinates morphogenesis and progenitor cell fate and regulates embryonic stem cell differentiation. Proc Natl Acad Sci USA. 2007;104:12029-12034.
98. Lee J, Petris MJ, Thiele DJ. Characterization of mouse embryonic cells deficient in the Ctr1 high affinity copper transporter. Identification of a Ctr1-independent copper transport system. J Biol Chem. 2002;277:40253-40259.
99. Kim H, Son HY, Bailey SM, Lee J. Deletion of hepatic Ctr1 reveals its function in copper acquisition and compensatory mechanisms for copper homeostasis. Am J Physiol Gastrointest Liver Physiol. 2009;296:G356-364.
100. Guo Y, Smith K, Lee J, Thiele DJ, Petris MJ. Identification of methionine-rich clusters that regulate copper-stimulated endocytosis of the human Ctr1 copper transporter. J Biol Chem. 2004;279:17428-17433.
101. Klomp AE, Juijn JA, van der Gun LT, van den Berg IE, Berger R, Klomp LW. The N-terminus of the human copper transporter 1 (hCTR1) is localized extracellularly, and interacts with itself. Biochem J. 2003;370:881-889.
102. Puig S, Lee J, Lau M, Thiele DJ. Biochemical and genetic analyses of yeast and human high affinity copper transporters suggest a conserved mechanism for copper uptake. J Biol Chem. 2002;277:26021-26030.
103. Eisses JF, Kaplan JH. Themechanism of copper uptakemediated by human CTR1: a mutational analysis. J Biol Chem. 2005;280:37159-37168.
104. Aller SG, Eng ET, De Feo CJ, Unger VM. Eukaryotic CTR copper uptake transporters require two faces of the third transmembrane domain for helix packing, oligomerization, and function. J Biol Chem. 2004;279:53435-53441.
105. Aller SG, Unger VM. Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture. Proc Natl Acad Sci USA. 2006;103:3627-3632.
106. De Feo CJ, Aller SG, Siluvai GS, Blackburn NJ, Unger VM. Three-dimensional structure of the human copper transporter hCTR1. Proc Natl Acad Sci USA. 2009;106:4237-4242.
107. Klomp AE, Tops BB, Van Denberg IE, Berger R, Klomp LW. Biochemical characterization and subcellular localization of human copper transporter 1 (hCTR1). Biochem J. 2002; 364:497-505.
108. Linder MC. Biochemistry of Copper, 1st edn. Berlin: Springer; 1991.
109. Kuo YM, Gybina AA, Pyatskowit JW, Gitschier J, Prohaska JR. Copper transport protein (Ctr1) levels in mice are tissue specific and dependent on copper status. J Nutr. 2006;136:21-26.
110. Zimnicka AM, Maryon EB, Kaplan JH. Human copper transporter hCTR1 mediates basolateral uptake of copper into enterocytes: implications for copper homeostasis. J Biol Chem. 2007;282:26471-26480.
111. Gunshin H, Mackenzie B, Berger UV, et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997;388:482-488.
112. Canonne-Hergaux F, Fleming MD, Levy JE, et al. The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood. 2000;96:3964-3970.
113. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc Natl Acad Sci USA. 1998;95:1148-1153.
114. Beaumont C, Delaunay J, Hetet G, Grandchamp B, de Montalembert M, Tchernia G. Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood. 2006;107:4168-4170.
115. Iolascon A, d'Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C.Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood. 2006;107:349-354.
116. Mims MP, Guan Y, Pospisilova D, et al. Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood. 2005;105:1337-1342.
117. Ohgami RS, Campagna DR, McDonald A, Fleming MD. The Steap proteins are metalloreductases. Blood. 2006;108: 1388-1394.
118. McKie AT, Barrow D, Latunde-Dada GO, et al. An ironregulated ferric reductase associated with the absorption of dietary iron. Science. 2001;291:1755-1759.
119. Wyman S, Simpson RJ, McKie AT, Sharp PA. Dcytb (Cybrd1) functions as both a ferric and a cupric reductase in vitro. FEBS Lett. 2008;582:1901-1906.
120. Rees EM, Thiele DJ. Identification of a vacuole-associated metalloreductase and its role in Ctr2-mediated intracellular copper mobilization. J Biol Chem. 2007;282:21629-21638.
121. Hardman B, Michalczyk A, Greenough M, Camakaris J, Mercer JF, Ackland ML. Hormonal regulation of the Menkes and Wilson copper-transporting ATPases in human placental Jeg-3 cells. Biochem J. 2007;402:241-250. (Pubitemid 46383421)
122. Mena NP, Esparza A, Tapia V, Valdes P, Nunez MT. Hepcidin inhibits apical iron uptake in intestinal cells. Am J Physiol Gastrointest Liver Physiol. 2008;294:G192-G198.
123. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA. 2001;98:8780-8785.
124. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liverspecific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811-7819.
125. Weiss KH, Wurz J, Gotthardt D, Merle U, Stremmel W, Fullekrug J. Localization of the Wilson disease protein in murine intestine. J Anat. 2008;213:232-240.
126. Leary SC,Winge DR, Cobine PA. "Pulling the plug"on cellular copper: the role of mitochondria in copper export. Biochim Biophys Acta. 2009;1793:146-153.
127. Muller P, van Bakel H, van de Sluis B, Holstege F, Wijmenga C, Klomp LW. Gene expression profiling of liver cells after copper overload in vivo and in vitro reveals new copper-regulated genes. J Biol Inorg Chem. 2007;12:495-507.
128. Lee J, Prohaska JR, Dagenais SL, Glover TW, Thiele DJ. Isolation of a murine copper transporter gene, tissue specific expression and functional complementation of a yeast copper transport mutant. Gene. 2000;254:87-96.
129. Yuzbasiyan-Gurkan V, Grider A, Nostrant T, Cousins RJ, Brewer GJ. Treatment ofWilson's disease with zinc: X. Intestinal metallothionein induction. J Lab Clin Med. 1992; 120:380-386.
130. Irato P, Albergoni V. Interaction between copper and zinc in metal accumulation in rats with particular reference to the synthesis of induced-metallothionein. Chem Biol Interact. 2005;155:155-164.
131. Santon A, Irato P, Medici V, D'Incà R, Albergoni V, Sturniolo GC. Effect and possible role of Zn treatment in LEC rats, an animal model of Wilson's disease. Biochim Biophys Acta. 2003;1637:91-97.
132. Zhang B, Georgiev O, Hagmann M, et al. Activity of metalresponsive transcription factor 1 by toxic heavy metals and H2O2 in vitro ismodulated bymetallothionein. Mol Cell Biol. 2003;23:8471-8485.
133. Gonzalez BP, Nino Fong R, Gibson CJ, Fuentealba IC, Cherian MG. Zinc supplementation decreases hepatic copper accumulation in LEC rat: amodel ofWilson's disease. Biol Trace Elem Res. 2005;105:117-134.
134. Klein D, Lichtmannegger J, Heinzmann U, Muller-Hocker J, Michaelsen S, Summer KH. Association of copper to metallothionein in hepatic lysosomes of Long-Evans cinnamon (LEC) rats during the development of hepatitis [see comments]. Eur J Clin Invest. 1998;28:302-310.
135. Klein D, Michaelsen S, Sato S, Luz A, Stampfl A, Summer KH. Binding of Cu to metallothionein in tissues of the LEC rat with inherited abnormal copper accumulation. Arch Toxicol. 1997;71:340-343.