Expression and function of iron-regulatory proteins in retina

IUBMB Life

Volumn 62, Issue 5, 2010, Pages 363-370

  Gnana Prakasam, Jaya P ^a   Martin, Pamela M ^a   Smith, Sylvia B ^a   Ganapathy, Vadivel ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

Age related macular degeneration; Hemochromatosis; Iron toxicity; Oxidative damage; Retina

Indexed keywords

FERROPORTIN; HEMOJUVELIN; HEPCIDIN; HFE PROTEIN; TRANSFERRIN RECEPTOR 2;

ACERULOPLASMINEMIA; BACTERIAL INFECTION; BLOOD RETINA BARRIER; GENE EXPRESSION; GENE MUTATION; GENETIC DISORDER; HEMOCHROMATOSIS; HOMEOSTASIS; HUMAN; IRON OVERLOAD; IRON STORAGE; NONHUMAN; PIGMENT EPITHELIUM; PROTEIN EXPRESSION; RETINA; RETINA MACULA AGE RELATED DEGENERATION; REVIEW; SYSTEMIC CIRCULATION; VIRUS INFECTION;

ANIMALS; ANTIMICROBIAL CATIONIC PEPTIDES; BACTERIAL INFECTIONS; BLOOD-RETINAL BARRIER; CATION TRANSPORT PROTEINS; FERRITINS; HEMOCHROMATOSIS; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IRON-REGULATORY PROTEINS; MACULAR DEGENERATION; MEMBRANE PROTEINS; MICE; PIGMENT EPITHELIUM OF EYE; RETINA; RETINAL DISEASES; VIRUS DISEASES;

BACTERIA (MICROORGANISMS);

EID: 77953569954     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.326     Document Type: Review

References (68)

1. Miret, S., Simpson, R. J., and Mckie, A. T. (2003) Physiology and molecular biology of dietary iron absorption. Annu. Rev. Nutr. 23, 283-301.
2. Centers for Disease Control and Prevention (1998) CDC recommendations to prevent and control iron deficiency in the United States. MMWR Recomm. Rep. 47, 1-29.
3. Halliwell, B. and Gutteridge, J. M. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219, 1-14.
4. Anderson, G. J., Vulpe, C. D. (2002) Regulation of intestinal iron transport. In Molecular and Cellular Iron Transport. (Templeton, D. M., ed.). pp. 559-596, Marcel Dekker, New York.
5. Moiseyev, G., Chen, Y., Takahashi, Y., Wu, B. X., and Ma, J. X. (2005) RPE65 is the isomerohydrolase in the retinoid visual cycle. Proc. Natl. Acad. Sci. USA 102, 12413-12418.
6. Chen, H., Lukas, T. J., Du, N., Suyeoka, G., and Neufeld, A. H. (2009) Dysfunction of the retinal pigment epithelium wSith age: increased iron decreases phagocytosis and lysosomal activity. Invest. Opthalmol. Vis. Sci. 50, 1895-1902.
7. Cao, H., Chen, J., Krueger, E. W., and Mcniven, M. A. (2010) Srcmediated phosphorylation of dynamin and cortactin regulates the "constitutive" endocytosis of transferrin. Mol. Cell. Biol. 30, 781-792.
8. Puri, C. (2009) Loss of myosin VI no insert isoform (NoI) induces a defect in clathrin-mediated endocytosis and leads to caveolar endocyto-sis of transferrin receptor. J. Biol. Chem. 284, 34998-35014.
9. Kawabata, H., Yang, R., Hirama, T., Vuong, P. T., Kawano, S., Gom-bart, A. F., and Koeffler, H. P. (1999) Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J. Biol. Chem. 274, 20826-20832.
10. Camaschella, C., Roetto, A., Calí, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., and Gasparini, P. (2000) The gene TfR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat. Genet. 25, 14-15.
11. Fleming, R. E., Ahmann, J. R., Migas, M. C., Waheed, A., Koeffler, H. P., Kawabata, H., Britton, R. S., Bacon, B. R., and Sly, W. S. (2002) Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochro-matosis. Proc. Natl. Acad. Sci. USA 99, 10653-10658.
12. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., and Hediger, M. A. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482-488.
13. Yefimova, M. G., Jeanny, J. C., Guillonneau, X., Keller, N., Nguyen-Legros, J., Sergeant, C., Guillou, F., and Courtois, Y. (2000) Iron, ferri-tin, transferrin, and transferrin receptor in the adult rat retina. Invest. Ophthalmol. Vis. Sci. 41, 2343-2351.
14. Martin, P. M., Gnana-Prakasam, J. P., Roon, P., Smith, R. G., Smith, S. B., and Ganapathy, V. (2006) Expression and polarized localization of the hemochromatosis gene product HFE in retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 47, 4238-4244.
15. He, X., Hahn, P., Iacovelli, J., Wong, R., King, C., Bhisitkul, R., Massaro-Giordano, M., and Dunaief, J. L. (2007) Iron homeostasis and toxicity in retinal degeneration. Prog. Retin. Eye. Res. 26, 649-673.
16. Li, J. Y., Paragas, N., Ned, R. M., Qiu, A., Viltard, M., Leete, T., Drexler, I. R., Chen, X., Sanna-Cherchi, S., Mohammed, F., Williams, D., Lin, C. S., Schmidt-Ott, K. M., Andrews, N. C., and Barasch, J. (2009) Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev. Cell. 16, 35-46.
17. Lee, J. H., Jang, H., Cho, E. J., and Youn, H. D. (2009) Ferritin binds and activates p53 under oxidative stress. Biochem. Biophys. Res. Commun. 389, 399-404.
18. Coffman, L. G., Parsonage, D., D'agostino, R., Torti, F. M., and Torti, S. V. (2009) Regulatory effects of ferritin on angiogenesis. Proc. Natl. Acad. Sci. USA 106, 570-575.
19. Beaumont, C., Leneuve, P., and Devaux, I. (1995) Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nat. Genet. 11, 444-446.
20. Girelli, D., Corrocher, R., and Bisceglia, L. (1995) Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene (the 'Verona mutation'). Blood 86, 4050-4053.
21. Hahn, P., Dentchev, T., Qian, Y., Rouault, T., Harris, Z. L., and Dunaief, J. L. (2004) Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina. Mol. Vis. 10, 598-607.
22. Rice, A. E., Mendez, M. J., Hokanson, C. A., Rees, D. C., and Björkman, P. J. (2009) Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J. Mol. Biol. 386, 717-732.
23. Hahn, P., Qian, Y., Dentchev, T., Chen, L., Beard, J., Harris, Z. L., and Dunaief, J. L. (2004) Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration. Proc. Natl. Acad. Sci. USA 101, 13850-13855.
24. Ganz, T. (2006) Hepcidin and its role in regulating systemic iron metabolism. Hematol. Am. Soc. Hematol. Educ. Program 507, 29-35.
25. Gagliardo, B., Kubat, N., Faye, A., Jaouen, M., Durel, B., Deschemin, J. C., Canonne-Hergaux, F., Sari, M. A., and Vaulont, S. (2009) Prohepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process. J. Hepatol. 50, 394-401.
26. De Domenico, I., Lo, E., Ward, D. M., and Kaplan, J. (2009) Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2. Proc. Natl. Acad. Sci. USA 106, 3800-3805.
27. Peslova, G., Petrak, J., Kuzelova, K., Hrdy, I., Halada, P., Kuchel, P. W., Soe-Lin, S., Ponka, P., Sutak, R., Becker, E., Huang, M. L., Rahmanto, Y. S., Richardson, D. R., and Vyoral, D. (2009) Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macro-globulin in blood. Blood 113, 6225-6236.
28. Darshan, D. and Anderson, G. J. (2009) Interacting signals in the control of hepcidin expression. Biometals 22, 77-87.
29. Vecchi, C., Montosi, G., Zhang, K., Lamberti, I., Duncan, S. A., Kaufman, R. J., and Pietrangelo, A. (2009) ER stress controls iron metabolism through induction of hepcidin. Science 325, 877-880.
30. Oliveira, S. J., Pinto, J. P., Picarote, G., Costa, V. M., Carvalho, F., Rangel, M., De Sousa, M., and De Almeida, S. F. (2009) ER stress-in-ducible factor CHOP affects the expression of hepcidin by modulating C/EBPalpha activity. PLoS One 4, e6618.
31. Gnana-Prakasam, J. P., Martin, P. M., Mysona, B. A., Roon, P., Smith, S. B., and Ganapathy, V. (2008) Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe. Biochem. J. 411, 79-88.
32. Fleming, R. E. and Britton, R. S. (2006) Iron imports. VI. HFE and regulation of intestinal iron absorption. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G590-G594.
33. Vujic Spasic, M., Kiss, J., Herrmann, T., Galy, B., Martinache, S., Stolte, J., Gröne, H. J., Stremmel, W., Hentze, M. W., and Muckenthaler, M. U. (2008) Hfe acts in hepatocytes to prevent hemochromatosis. Cell. Metab. 7, 173-178.
34. Bhatt, L., Horgan, C. P., and Mccaffrey, M. W. (2009) Knockdown of beta2-microglobulin perturbs the subcellular distribution of HFE and hepcidin. Biochem. Biophys. Res. Commun. 378, 727-731.
35. Gao, J., Chen, J., Kramer, M., Tsukamoto, H., Zhang, A. S., and Enns, C. A. (2009) Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell. Metab. 9, 217-227.
36. Wallace, D. F., Summerville, L., Crampton, E. M., Frazer, D. M., Anderson, G. J., and Subramaniam, V. N. (2009) Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload. Hepatology 50, 1992-2000.
37. Kautz, L., Meynard, D., Besson-Fournier, C., Darnaud, V., Al Saati, T., Coppin, H., and Roth, M. P. (2009) BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression. Blood 114, 2515-2520.
38. Corradini, E., Garuti, C., Montosi, G., Ventura, P., Andriopoulos, B., Lin, H. Y., Pietrangelo, A., and Babitt, J. L. (2009) Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis. Gastroenterology 137, 1489-1497.
39. Xia, Y., Babitt, J. L., Sidis, Y., Chung, R. T., and Lin, H. Y. (2008) Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood 111, 5195-5204.
40. Zhang, A. S., Yang, F., Meyer, K., Hernandez, C., Chapman-Arvedson, T., Bjorkman, P. J., and Enns, C. A. (2008) Neogenin-mediated hemoju-velin shedding occurs after hemojuvelin traffics to the plasma membrane. J. Biol. Chem. 283, 17494-17502.
41. Ramsay, A. J., Hooper, J. D., Folgueras, A. R., Velasco, G., and López-Otín, C. (2009) Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis. Haematologica 94, 840-849.
42. Andriopoulos, B., Corradini, E., Xia, Y., Faasse, S. A., Chen, S., Grgur-evic, L., Knutson, M. D., Pietrangelo, A., Vukicevic, S., Lin, H. Y., and Babitt, J. L. (2009) BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat. Genet. 41, 482-487.
43. Casanovas, G., Mleczko-Sanecka, K., Altamura, S., Hentze, M. W., and Muckenthaler, M. U. (2009) Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD. J. Mol. Med. 87, 471-480.
44. Zhang, A. S., Yang, F., Wang, J., Tsukamoto, H., and Enns, C. A. (2009) Hemojuvelin-neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression. J. Biol. Chem. 284, 22580-22589.
45. Ramey, G., Deschemin, J. C., and Vaulont, S. (2009) Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holo-transferrin in primary mouse hepatocytes. Haematologica 94, 765-772.
46. Gnana-Prakasam, J. P., Martin, P. M., Zhang, M., Atherton, S. S., Smith, S. B., and Ganapathy, V. (2009) Expression of the iron-regulatory protein hemojuvelin in retina and its regulation during cytomegalo-virus infection. Biochem. J. 419, 533-543.
47. Yamaguchi, K., Takahashi, S., Kawanami, T., Kato, T., and Sasaki, H. (1998) Retinal degeneration in hereditary ceruloplasmin deficiency. Ophthalmologica 212, 11-14.
48. Harris, Z. L., Takahashi, Y., Miyajima, H., Serizawa, M., Macgillivray, R. T., and Gitlin, J. D. (1995) Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc. Natl. Acad. Sci. USA 92, 2539-2543.
49. Donovan, A. and Andrews, N. C. (2004) The molecular regulation of iron metabolism. Hematol. J. 5, 373-380.
50. Fleming, R. E., Britton, R. S., Waheed, A., Sly, W. S., and Bacon, B. R. (2005) Pathophysiology of hereditary hemochromatosis. Semin. Liver Dis. 25, 411-419.
51. Beutler, E. (2006) Hemochromatosis: genetics and pathophysiology. Annu. Rev. Med. 57, 331-347.
52. Pietrangelo, A. (2005) Non-HFE hemochromatosis. Semin. Liver Dis. 25, 450-460.
53. Davies, G., Dymock, I., Harry, J., and Williams, R. (1972) Deposition of melanin and iron in ocular structures in hemochromatosis. Br. J. Ophthalmol. 56, 338-342.
54. Roth, A. M. and Foos, R. Y. (1972) Ocular pathologic changes in primary hemochromatosis. Arch. Ophthalmol. 87, 507-514.
55. Gnana-Prakasam, J. P., Thangaraju, M., Liu, K., Ha, Y., Martin, P. M., Smith, S. B., and Ganapathy, V. (2009) Absence of iron-regulatory protein HFE results in hyper-proliferation of retinal pigment epithelium mediated by induction of cystine/glutamate transporter. Biochem. J. 424, 243-252.
56. Hadziahmetovic, M., Song, Y., Grieco, S., Vaulont, S., and Dunaief, J. L. (2009). Hepcidin deficient mice have an age-related retinal iron accumulation with RPE hypertrophy/autofluorescence ARVO 2009. Annual meeting, Fort Lauderdale, FL. Poster D896.
57. Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., and Adamis, A. P. (2003) Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Surv. Ophthalmol. 48, 257-293.
58. Montezuma, S. R., Sobrin, L., and Seddon, J. M. (2007) Review of genetics of age-related macular degeneration. Semin. Ophthalmol. 22, 229-240.
59. Beatty, S., Koh, H., Phil, M., Henson, D., and Boulton, M. (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 45, 115-134.
60. AREDS (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol. 119, 1417-1436.
61. Dentchev, T., Hahn, P., and Dunaief, J. L. (2005) Strong labeling for iron and the iron-handling proteins ferritin and ferroportin in the photo-receptor layer in age-related macular degeneration. Arch. Ophthalmol. 123, 1745-1746.
62. Hahn, P., Milam, A. H., and Dunaief, J. L. (2003) Maculas affected by age-related macular degeneration contain increased chelatable iron in the retinal pigment epithelium and Bruch's membrane. Arch. Ophthalmol. 121, 1099-1105.
63. Hadziahmetovic, M., Denntchev, T., Song, Y., Haddad, N., He, X., Hahn, P., Pratico, D., Wen, R., Harris, Z. L., Lambris, J. D., Beard, J., and Dunaief, J. L. (2008) Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD. Invest. Ophthalmol. Vis. Sci. 49, 2728-2736.
64. Hammer, A., Ferro, M., Tillian, H. M., Tatzber, F., Zollner, H., Schauenstein, E., and Schaur, R. J. (1997) Effect of oxidative stress by iron on 4-hydroxynonenal formation and proliferative activity in hepatomas of different degrees of differentiation. Free. Rad. Biol. Med. 23, 26-33.
65. Houglum, K., Filip, M., Witztum, J. L., and Chojkier, M. (1990) Malon-dialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J. Clin. Invest. 86, 1991-1998.
66. Arieh, S. V. B., Laham, N., Schechter, C., Yewdell, J. W., Coligan, J. E., and Ehrlich, R. (2003) A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules. Blood 101, 2858-2864.
67. Chevalier, M. S. and Johnson, D. C. (2003) Human cytomegalovirus US3 chimeras containing US2 cytosolic residues acquire major histo-compatibility class I and II protein degradation properties. J. Virol. 77, 4731-4738.
68. Scholz, M., Doerr, H. W., and Cinatl, J. (2003) Human cytomegalovirus retinitis: pathogenicity, immune invasion and persistence. Trends. Microbiol. 11, 171-178.