An overview of molecular basis of iron metabolism regulation and the associated pathologies

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1852, Issue 7, 2015, Pages 1347-1359

  Silva, Bruno ^a   Faustino, Paula ^a  

^a NATIONAL INSTITUTE OF HEALTH DR RICARDO JORGE   (Portugal)

Author keywords

Hemochromatosis; Hepcidin; Iron; Iron deficiency; Post transcriptional regulation

Indexed keywords

ERYTHROPOIETIN; GROWTH DIFFERENTIATION FACTOR 15; HEPCIDIN; IRON; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2; MICRORNA; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; IRON-BINDING PROTEINS; IRON-REGULATORY PROTEINS;

ALTERNATIVE RNA SPLICING; ANEMIA; ERYTHROPOIESIS; GENETIC TRANSCRIPTION; HEMOGLOBIN SYNTHESIS; HOMEOSTASIS; HUMAN; HYPOXIA; INFECTION; INFLAMMATION; IRON ABSORPTION; IRON INTAKE; IRON METABOLISM; IRON METABOLISM DISORDER; IRON OVERLOAD; IRON STORAGE; IRON TRANSPORT; METABOLIC REGULATION; MOLECULAR BIOLOGY; MOLECULAR PATHOLOGY; PATHOLOGY; POLYADENYLATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; REGULATORY MECHANISM; REVIEW; RNA PROCESSING; ANIMALS; GENETICS; HUMANS; IRON METABOLISM DISORDERS; METABOLISM;

ANIMALS; HUMANS; IRON; IRON METABOLISM DISORDERS; IRON-BINDING PROTEINS; IRON-REGULATORY PROTEINS;

EID: 84927154486     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2015.03.011     Document Type: Review

References (192)

1. Frey P.A., Reed G.H. The ubiquity of iron. ACS Chem. Biol. 2012, 7:1477-1481.
2. Lane N., Martin W.F. The origin of membrane bioenergetics. Cell 2012, 151:1406-1416.
3. Sleep N.H., Meibom A., Fridriksson T., Coleman R.G., Bird D.K. H2-rich fluids from serpentinization: geochemical and biotic implications. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:12818-12823.
4. Emerson D., Fleming E.J., McBeth J.M. Iron-oxidizing bacteria: an environmental and genomic perspective. Annu. Rev. Microbiol. 2010, 64:561-583.
5. Bretschger O., Obraztsova A., Sturm C.A., Chang I.S., Gorby Y.A., Reed S.B., Culley D.E., Reardon C.L., Barua S., Romine M.F., Zhou J., Beliaev A.S., Bouhenni R., Saffarini D., Mansfeld F., Kim B.H., Fredrickson J.K., Nealson K.H. Current production and metal oxide reduction by Shewanella oneidensis MR-1 wild type and mutants. Appl. Environ. Microbiol. 2007, 73:7003-7012.
6. Roche B., Aussel L., Ezraty B., Mandin P., Py B., Barras F. Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity. Biochim. Biophys. Acta 2013, 1827:455-469.
7. Gunsalus I.C., Sligar S.G., Nordlund T., Frauenfelder H. Oxygen sensing heme proteins: monoxygenases, myoglobin and hemoglobin. Adv. Exp. Med. Biol. 1977, 78:37-50.
8. White M.F., Dillingham M.S. Iron-sulphur clusters in nucleic acid processing enzymes. Curr. Opin. Struct. Biol. 2012, 22:94-100.
9. Miller D.D., Berner L.A. Is solubility in vitro a reliable predictor of iron bioavailability?. Biol. Trace Elem. Res. 1989, 19:11-24.
10. Chu B.C., Garcia-Herrero A., Johanson T.H., Krewulak K.D., Lau C.K., Peacock R.S., Slavinskaya Z., Vogel H.J. Siderophore uptake in bacteria and the battle for iron with the host; a bird's eye view. Biometals 2010, 23:601-611.
11. Walling C., Partch R.E., Weil T. Kinetics of the decomposition of hydrogen peroxide catalyzed by ferric ethylenediaminetetraacetate complex. Proc. Natl. Acad. Sci. U. S. A. 1975, 72:140-142.
12. Park C.H., Bacon B.R., Brittenham G.M., Tavill A.S. Pathology of dietary carbonyl iron overload in rats. Lab. Invest. 1987, 57:555-563.
13. Charlton R.W., Bothwell T.H. Iron absorption. Annu. Rev. Med. 1983, 34:55-68.
14. Crichton R.R., Charloteaux-Wauters M. Iron transport and storage. Eur. J. Biochem. 1987, 164:485-506.
15. Thorstensen K., Romslo I. The role of transferrin in the mechanism of cellular iron uptake. Biochem. J. 1990, 271:1-9.
16. Ganz T. Hepcidin-a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract. Res. Clin. Haematol. 2005, 18:171-182.
17. Sharp P.A. Intestinal iron absorption: regulation by dietary & systemic factors. Int. J. Vitam. Nutr. Res. 2010, 80:231-242.
18. Laftah A.H., Latunde-Dada G.O., Fakih S., Hider R.C., Simpson R.J., McKie A.T. Haem and folate transport by proton-coupled folate transporter/haem carrier protein 1 (SLC46A1). Br. J. Nutr. 2009, 101:1150-1156.
19. San Martin C.D., Garri C., Pizarro F., Walter T., Theil E.C., Nunez M.T. Caco-2 intestinal epithelial cells absorb soybean ferritin by mu2 (AP2)-dependent endocytosis. J. Nutr. 2008, 138:659-666.
20. McKie A.T., Barrow D., Latunde-Dada G.O., Rolfs A., Sager G., Mudaly E., Mudaly M., Richardson C., Barlow D., Bomford A., Peters T.J., Raja K.B., Shirali S., Hediger M.A., Farzaneh F., Simpson R.J. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 2001, 291:1755-1759.
21. Ohgami R.S., Campagna D.R., McDonald A., Fleming M.D. The Steap proteins are metalloreductases. Blood 2006, 108:1388-1394.
22. Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F., Nussberger S., Gollan J.L., Hediger M.A. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 1997, 388:482-488.
23. Galy B., Ferring-Appel D., Becker C., Gretz N., Grone H.J., Schumann K., Hentze M.W. Iron regulatory proteins control a mucosal block to intestinal iron absorption. Cell Rep. 2013, 3:844-857.
24. Le N.T., Richardson D.R. Ferroportin1: a new iron export molecule?. Int. J. Biochem. Cell Biol. 2002, 34:103-108.
25. Yeh K.Y., Yeh M., Mims L., Glass J. Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 296:G55-G65.
26. Brittin G.M., Chee Q.T. Relation of ferroxidase (ceruloplasmin) to iron absorption. J. Lab. Clin. Med. 1969, 74:53-59.
27. Young S., Bomford A. Transferrin and cellular iron exchange. Clin. Sci. (Lond.) 1984, 67:273-278.
28. Brown P.J., Johnson P.M. Isolation of a transferrin receptor structure from sodium deoxycholate-solubilized human placental syncytiotrophoblast plasma membrane. Placenta 1981, 2:1-10.
29. Fleming M.D., Romano M.A., Su M.A., Garrick L.M., Garrick M.D., Andrews N.C. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:1148-1153.
30. Hershko C., Graham G., Bates G.W., Rachmilewitz E.A. Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br. J. Haematol. 1978, 40:255-263.
31. Grootveld M., Bell J.D., Halliwell B., Aruoma O.I., Bomford A., Sadler P.J. Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. J. Biol. Chem. 1989, 264:4417-4422.
32. Liuzzi J.P., Aydemir F., Nam H., Knutson M.D., Cousins R.J. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:13612-13617.
33. Andrews P.A. Disorders of iron metabolism. N. Engl. J. Med. 2000, 342:1293. (author reply 1294).
34. Shi H., Bencze K.Z., Stemmler T.L., Philpott C.C. A cytosolic iron chaperone that delivers iron to ferritin. Science 2008, 320:1207-1210.
35. Sheftel A.D., Zhang A.S., Brown C., Shirihai O.S., Ponka P. Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 2007, 110:125-132.
36. Shaw G.C., Cope J.J., Li L., Corson K., Hersey C., Ackermann G.E., Gwynn B., Lambert A.J., Wingert R.A., Traver D., Trede N.S., Barut B.A., Zhou Y., Minet E., Donovan A., Brownlie A., Balzan R., Weiss M.J., Peters L.L., Kaplan J., Zon L.I., Paw B.H. Mitoferrin is essential for erythroid iron assimilation. Nature 2006, 440:96-100.
37. Liu X., Theil E.C. Ferritin as an iron concentrator and chelator target. Ann. N. Y. Acad. Sci. 2005, 1054:136-140.
38. Levi S., Corsi B., Bosisio M., Invernizzi R., Volz A., Sanford D., Arosio P., Drysdale J. A human mitochondrial ferritin encoded by an intronless gene. J. Biol. Chem. 2001, 276:24437-24440.
39. Larson J.A., Howie H.L., So M. Neisseria meningitidis accelerates ferritin degradation in host epithelial cells to yield an essential iron source. Mol. Microbiol. 2004, 53:807-820.
40. Mehlhase J., Sandig G., Pantopoulos K., Grune T. Oxidation-induced ferritin turnover in microglial cells: role of proteasome. Free Radic. Biol. Med. 2005, 38:276-285.
41. Mancias J.D., Wang X., Gygi S.P., Harper J.W., Kimmelman A.C. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 2014, 509:105-109.
42. Nilsson R., Schultz I.J., Pierce E.L., Soltis K.A., Naranuntarat A., Ward D.M., Baughman J.M., Paradkar P.N., Kingsley P.D., Culotta V.C., Kaplan J., Palis J., Paw B.H., Mootha V.K. Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis. Cell Metab. 2009, 10:119-130.
43. Dowdle W.E., Nyfeler B., Nagel J., Elling R.A., Liu S., Triantafellow E., Menon S., Wang Z., Honda A., Pardee G., Cantwell J., Luu C., Cornella-Taracido I., Harrington E., Fekkes P., Lei H., Fang Q., Digan M.E., Burdick D., Powers A.F., Helliwell S.B., D'Aquin S., Bastien J., Wang H., Wiederschain D., Kuerth J., Bergman P., Schwalb D., Thomas J., Ugwonali S., Harbinski F., Tallarico J., Wilson C.J., Myer V.E., Porter J.A., Bussiere D.E., Finan P.M., Labow M.A., Mao X., Hamann L.G., Manning B.D., Valdez R.A., Nicholson T., Schirle M., Knapp M.S., Keaney E.P., Murphy L.O. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 2014, 16:1069-1079.
44. Pollard J.W. Trophic macrophages in development and disease. Nat. Rev. Immunol. 2009, 9:259-270.
45. Low P.S., Waugh S.M., Zinke K., Drenckhahn D. The role of hemoglobin denaturation and band 3 clustering in red blood cell aging. Science 1985, 227:531-533.
46. Pantaleo A., Giribaldi G., Mannu F., Arese P., Turrini F. Naturally occurring anti-band 3 antibodies and red blood cell removal under physiological and pathological conditions. Autoimmun. Rev. 2008, 7:457-462.
47. Lee S.J., Park S.Y., Jung M.Y., Bae S.M., Kim I.S. Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver. Blood 2011, 117:5215-5223.
48. Bosman G.J., Willekens F.L., Werre J.M. Erythrocyte aging: a more than superficial resemblance to apoptosis?. Cell. Physiol. Biochem. 2005, 16:1-8.
49. Poss K.D., Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:10919-10924.
50. Kristiansen M., Graversen J.H., Jacobsen C., Sonne O., Hoffman H.J., Law S.K., Moestrup S.K. Identification of the haemoglobin scavenger receptor. Nature 2001, 409:198-201.
51. Soe-Lin S., Apte S.S., Andriopoulos B., Andrews M.C., Schranzhofer M., Kahawita T., Garcia-Santos D., Ponka P. Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:5960-5965.
52. Harris Z.L., Durley A.P., Man T.K., Gitlin J.D. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:10812-10817.
53. Finch C. Regulators of iron balance in humans. Blood 1994, 84:1697-1702.
54. Gavin M.W., McCarthy D.M., Garry P.J. Evidence that iron stores regulate iron absorption-a setpoint theory. Am. J. Clin. Nutr. 1994, 59:1376-1380.
55. Nicolas G., Bennoun M., Devaux I., Beaumont C., Grandchamp B., Kahn A., Vaulont S. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:8780-8785.
56. Lin L., Valore E.V., Nemeth E., Goodnough J.B., Gabayan V., Ganz T. Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood 2007, 110:2182-2189.
57. Nicolas G., Chauvet C., Viatte L., Danan J.L., Bigard X., Devaux I., Beaumont C., Kahn A., Vaulont S. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 2002, 110:1037-1044.
58. 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.
59. Hunter H.N., Fulton D.B., Ganz T., Vogel H.J. The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis. J. Biol. Chem. 2002, 277:37597-37603.
60. Valore E.V., Ganz T. Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells Mol. Dis. 2008, 40:132-138.
61. Nemeth E., Tuttle M.S., Powelson J., Vaughn M.B., Donovan A., Ward D.M., Ganz T., Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004, 306:2090-2093.
62. Qiao B., Sugianto P., Fung E., Del-Castillo-Rueda A., Moran-Jimenez M.J., Ganz T., Nemeth E. Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metab. 2012, 15:918-924.
63. Park C.H., Valore E.V., Waring A.J., Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem. 2001, 276:7806-7810.
64. Swinkels D.W., Girelli D., Laarakkers C., Kroot J., Campostrini N., Kemna E.H., Tjalsma H. Advances in quantitative hepcidin measurements by time-of-flight mass spectrometry. PLoS One 2008, 3:e2706.
65. Kulaksiz H., Fein E., Redecker P., Stremmel W., Adler G., Cetin Y. Pancreatic beta-cells express hepcidin, an iron-uptake regulatory peptide. J. Endocrinol. 2008, 197:241-249.
66. Kulaksiz H., Theilig F., Bachmann S., Gehrke S.G., Rost D., Janetzko A., Cetin Y., Stremmel W. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. J. Endocrinol. 2005, 184:361-370.
67. Bekri S., Gual P., Anty R., Luciani N., Dahman M., Ramesh B., Iannelli A., Staccini-Myx A., Casanova D., Ben Amor I., Saint-Paul M.C., Huet P.M., Sadoul J.L., Gugenheim J., Srai S.K., Tran A., Le Marchand-Brustel Y. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006, 131:788-796.
68. Nguyen N.B., Callaghan K.D., Ghio A.J., Haile D.J., Yang F. Hepcidin expression and iron transport in alveolar macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol. 2006, 291:L417-L425.
69. Schmidt P.J., Toran P.T., Giannetti A.M., Bjorkman P.J., Andrews N.C. The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression. Cell Metab. 2008, 7:205-214.
70. Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B.K., 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.
71. Zhang A.S., Gao J., Koeberl D.D., Enns C.A. The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo. J. Biol. Chem. 2010, 285:16416-16423.
72. Xia Y., Babitt J.L., Sidis Y., Chung R.T., Lin H.Y. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood 2008, 111:5195-5204.
73. Babitt J.L., Huang F.W., Wrighting D.M., Xia Y., Sidis Y., Samad T.A., Campagna J.A., Chung R.T., Schneyer A.L., Woolf C.J., Andrews N.C., Lin H.Y. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat. Genet. 2006, 38:531-539.
74. Truksa J., Peng H., Lee P., Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:10289-10293.
75. Truksa J., Lee P., Beutler E. Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness. Blood 2009, 113:688-695.
76. Casanovas G., Mleczko-Sanecka K., Altamura S., Hentze M.W., Muckenthaler M.U. 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. (Berl.) 2009, 87:471-480.
77. Meynard D., Kautz L., Darnaud V., Canonne-Hergaux F., Coppin H., Roth M.P. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat. Genet. 2009, 41:478-481.
78. Andriopoulos B., Corradini E., Xia Y., Faasse S.A., Chen S., Grgurevic L., Knutson M.D., Pietrangelo A., Vukicevic S., Lin H.Y., Babitt J.L. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat. Genet. 2009, 41:482-487.
79. Kautz L., Meynard D., Monnier A., Darnaud V., Bouvet R., Wang R.H., Deng C., Vaulont S., Mosser J., Coppin H., Roth M.P. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 2008, 112:1503-1509.
80. Enns C.A., Ahmed R., Wang J., Ueno A., Worthen C., Tsukamoto H., Zhang A.S. Increased iron loading induces Bmp6 expression in the non-parenchymal cells of the liver independent of the BMP-signaling pathway. PLoS One 2013, 8:e60534.
81. Silvestri L., Pagani A., Camaschella C. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood 2008, 111:924-931.
82. Lin L., Nemeth E., Goodnough J.B., Thapa D.R., Gabayan V., Ganz T. Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site. Blood Cells Mol. Dis. 2008, 40:122-131.
83. Maxson J.E., Enns C.A., Zhang A.S. Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells. Blood 2009, 113:1786-1793.
84. Ramsay A.J., Hooper J.D., Folgueras A.R., Velasco G., Lopez-Otin C. Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis. Haematologica 2009, 94:840-849.
85. Silvestri L., Pagani A., Nai A., De Domenico I., Kaplan J., Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab. 2008, 8:502-511.
86. Zhang A.S., West A.P., Wyman A.E., Bjorkman P.J., Enns C.A. Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. J. Biol. Chem. 2005, 280:33885-33894.
87. Zhang A.S., Yang F., Wang J., Tsukamoto H., Enns C.A. Hemojuvelin-neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression. J. Biol. Chem. 2009, 284:22580-22589.
88. Enns C.A., Ahmed R., Zhang A.S. Neogenin interacts with matriptase-2 to facilitate hemojuvelin cleavage. J. Biol. Chem. 2012, 287:35104-35117.
89. Gross C.N., Irrinki A., Feder J.N., Enns C.A. Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation. J. Biol. Chem. 1998, 273:22068-22074.
90. Gao J., Chen J., Kramer M., Tsukamoto H., Zhang A.S., Enns C.A. Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab. 2009, 9:217-227.
91. Ramey G., Deschemin J.C., Vaulont S. Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes. Haematologica 2009, 94:765-772.
92. Gao J., Chen J., De Domenico I., Koeller D.M., Harding C.O., Fleming R.E., Koeberl D.D., Enns C.A. Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice. Blood 2010, 115:3374-3381.
93. D'Alessio F., Hentze M.W., Muckenthaler M.U. The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. J. Hepatol. 2012, 57:1052-1060.
94. Rishi G., Crampton E.M., Wallace D.F., Subramaniam V.N. In situ proximity ligation assays indicate that hemochromatosis proteins Hfe and transferrin receptor 2 (Tfr2) do not interact. PLoS One 2013, 8:e77267.
95. Wu X.G., Wang Y., Wu Q., Cheng W.H., Liu W., Zhao Y., Mayeur C., Schmidt P.J., Yu P.B., Wang F., Xia Y. HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression. Blood 2014, 124:1335-1343.
96. Nemeth E., Valore E.V., 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.
97. Rivera S., Nemeth E., Gabayan V., Lopez M.A., Farshidi D., Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood 2005, 106:2196-2199.
98. Lee P., Peng H., Gelbart T., Wang L., Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:1906-1910.
99. Inamura K., Matsuzaki Y., Uematsu N., Honda A., Tanaka N., Uchida K. Rapid inhibition of MAPK signaling and anti-proliferation effect via JAK/STAT signaling by interferon-alpha in hepatocellular carcinoma cell lines. Biochim. Biophys. Acta 2005, 1745:401-410.
100. Wrighting D.M., Andrews N.C. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006, 108:3204-3209.
101. Haase V.H. Hypoxic regulation of erythropoiesis and iron metabolism. Am. J. Physiol. Renal Physiol. 2010, 299:F1-F13.
102. Kewley R.J., Whitelaw M.L., Chapman-Smith A. The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int. J. Biochem. Cell Biol. 2004, 36:189-204.
103. Maxwell P.H., Wiesener M.S., Chang G.W., Clifford S.C., Vaux E.C., Cockman M.E., Wykoff C.C., Pugh C.W., Maher E.R., Ratcliffe P.J. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999, 399:271-275.
104. Lok C.N., Ponka P. Identification of a hypoxia response element in the transferrin receptor gene. J. Biol. Chem. 1999, 274:24147-24152.
105. Mukhopadhyay C.K., Mazumder B., Fox P.L. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency. J. Biol. Chem. 2000, 275:21048-21054.
106. Shah Y.M., Matsubara T., Ito S., Yim S.H., Gonzalez F.J. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab. 2009, 9:152-164.
107. Lee P.J., Jiang B.H., Chin B.Y., Iyer N.V., Alam J., Semenza G.L., Choi A.M. Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J. Biol. Chem. 1997, 272:5375-5381.
108. Braliou G.G., Verga Falzacappa M.V., Chachami G., Casanovas G., Muckenthaler M.U., Simos G. 2-Oxoglutarate-dependent oxygenases control hepcidin gene expression. J. Hepatol. 2008, 48:801-810.
109. Choi S.O., Cho Y.S., Kim H.L., Park J.W. ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPalpha and STAT-3. Biochem. Biophys. Res. Commun. 2007, 356:312-317.
110. Sonnweber T., Nachbaur D., Schroll A., Nairz M., Seifert M., Demetz E., Haschka D., Mitterstiller A.M., Kleinsasser A., Burtscher M., Trubsbach S., Murphy A.T., Wroblewski V., Witcher D.R., Mleczko-Sanecka K., Vecchi C., Muckenthaler M.U., Pietrangelo A., Theurl I., Weiss G. Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB. Gut 2014, 63:1951-1959.
111. Schito L., Rey S., Tafani M., Zhang H., Wong C.C., Russo A., Russo M.A., Semenza G.L. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. Proc. Natl. Acad. Sci. U. S. A. 2012, 109:E2707-E2716.
112. Jacobson L.O., Goldwasser E., Fried W., Plzak L.F. Studies on erythropoiesis. VII. The role of the kidney in the production of erythropoietin. Trans. Assoc. Am. Phys. 1957, 70:305-317.
113. Rankin E.B., Biju M.P., Liu Q., Unger T.L., Rha J., Johnson R.S., Simon M.C., Keith B., Haase V.H. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J. Clin. Invest. 2007, 117:1068-1077.
114. Ashby D.R., Gale D.P., Busbridge M., Murphy K.G., Duncan N.D., Cairns T.D., Taube D.H., Bloom S.R., Tam F.W., Chapman R., Maxwell P.H., Choi P. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 2010, 95:505-508.
115. Tanno T., Bhanu N.V., Oneal P.A., Goh S.H., Staker P., Lee Y.T., Moroney J.W., Reed C.H., Luban N.L., Wang R.H., Eling T.E., Childs R., Ganz T., Leitman S.F., Fucharoen S., Miller J.L. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat. Med. 2007, 13:1096-1101.
116. Tanno T., Porayette P., Sripichai O., Noh S.J., Byrnes C., Bhupatiraju A., Lee Y.T., Goodnough J.B., Harandi O., Ganz T., Paulson R.F., Miller J.L. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 2009, 114:181-186.
117. Casanovas G., Swinkels D.W., Altamura S., Schwarz K., Laarakkers C.M., Gross H.J., Wiesneth M., Heimpel H., Muckenthaler M.U. Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II. J. Mol. Med. (Berl.) 2011, 89:811-816.
118. Kautz L., Jung G., Valore E.V., Rivella S., Nemeth E., Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat. Genet. 2014, 46:678-684.
119. Patel N., Varghese J., Masaratana P., Latunde-Dada G.O., Jacob M., Simpson R.J., McKie A.T. The transcription factor ATOH8 is regulated by erythropoietic activity and regulates HAMP transcription and cellular pSMAD1,5,8 levels. Br. J. Haematol. 2014, 164:586-596.
120. Zhang D.L., Hughes R.M., Ollivierre-Wilson H., Ghosh M.C., Rouault T.A. A ferroportin transcript that lacks an iron-responsive element enables duodenal and erythroid precursor cells to evade translational repression. Cell Metab. 2009, 9:461-473.
121. Kawabata H., Yang R., Hirama T., Vuong P.T., Kawano S., Gombart A.F., Koeffler H.P. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J. Biol. Chem. 1999, 274:20826-20832.
122. Hubert N., Hentze M.W. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:12345-12350.
123. Roetto A., Di Cunto F., Pellegrino R.M., Hirsch E., Azzolino O., Bondi A., Defilippi I., Carturan S., Miniscalco B., Riondato F., Cilloni D., Silengo L., Altruda F., Camaschella C., Saglio G. Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-alpha and Tfr2-beta isoforms in different tissues. Blood 2010, 115:3382-3389.
124. Glisovic T., Bachorik J.L., Yong J., Dreyfuss G. RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett. 2008, 582:1977-1986.
125. Lutz C.S., Moreira A. Alternative mRNA polyadenylation in eukaryotes: an effective regulator of gene expression. Wiley Interdiscip. Rev. RNA 2011, 2:23-31.
126. Guo B., Brown F.M., Phillips J.D., Yu Y., Leibold E.A. Characterization and expression of iron regulatory protein 2 (IRP2). Presence of multiple IRP2 transcripts regulated by intracellular iron levels. J. Biol. Chem. 1995, 270:16529-16535.
127. Sanchez M., Bruguera M., Rodes J., Oliva R. Complete characterization of the 3' region of the human and mouse hereditary hemochromatosis HFE gene and detection of novel splicing forms. Blood Cells Mol. Dis. 2001, 27:35-43.
128. Martins R., Proenca D., Silva B., Barbosa C., Silva A.L., Faustino P., Romao L. Alternative polyadenylation and nonsense-mediated decay coordinately regulate the human HFE mRNA levels. PLoS One 2012, 7:e35461.
129. Nilsen T.W., Graveley B.R. Expansion of the eukaryotic proteome by alternative splicing. Nature 2010, 463:457-463.
130. Martins R., Silva B., Proenca D., Faustino P. Differential HFE gene expression is regulated by alternative splicing in human tissues. PLoS One 2011, 6:e17542.
131. Silva B., Ferreira J., Santos V., Baldaia C., Serejo F., Faustino P. The soluble form of HFE protein regulates hephaestin mRNA expression in the duodenum through an endocytosis-dependent mechanism. Biochim. Biophys. Acta 2014, 1842:2298-2305.
132. Tabuchi M., Tanaka N., Nishida-Kitayama J., Ohno H., Kishi F. Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol. Biol. Cell 2002, 13:4371-4387.
133. Patel B.N., Dunn R.J., David S. Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain. J. Biol. Chem. 2000, 275:4305-4310.
134. Anderson C.P., Shen M., Eisenstein R.S., Leibold E.A. Mammalian iron metabolism and its control by iron regulatory proteins. Biochim. Biophys. Acta 2012, 1823:1468-1483.
135. Samaniego F., Chin J., Iwai K., Rouault T.A., Klausner R.D. Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation. J. Biol. Chem. 1994, 269:30904-30910.
136. DeRusso P.A., Philpott C.C., Iwai K., Mostowski H.S., Klausner R.D., Rouault T.A. Expression of a constitutive mutant of iron regulatory protein 1 abolishes iron homeostasis in mammalian cells. J. Biol. Chem. 1995, 270:15451-15454.
137. Johnson D.C., Dean D.R., Smith A.D., Johnson M.K. Structure, function, and formation of biological iron-sulfur clusters. Annu. Rev. Biochem. 2005, 74:247-281.
138. Wallander M.L., Leibold E.A., Eisenstein R.S. Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim. Biophys. Acta 2006, 1763:668-689.
139. Guo B., Phillips J.D., Yu Y., Leibold E.A. Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J. Biol. Chem. 1995, 270:21645-21651.
140. Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.W., Kinch L.N., Li Q., Grishin N.V., Bruick R.K. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science 2009, 326:722-726.
141. Moroishi T., Nishiyama M., Takeda Y., Iwai K., Nakayama K.I. The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo. Cell Metab. 2011, 14:339-351.
142. Sammarco M.C., Ditch S., Banerjee A., Grabczyk E. Ferritin L and H subunits are differentially regulated on a post-transcriptional level. J. Biol. Chem. 2008, 283:4578-4587.
143. Lymboussaki A., Pignatti E., Montosi G., Garuti C., Haile D.J., Pietrangelo A. The role of the iron responsive element in the control of ferroportin1/IREG1/MTP1 gene expression. J. Hepatol. 2003, 39:710-715.
144. Casey J.L., Koeller D.M., Ramin V.C., Klausner R.D., Harford J.B. Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3' untranslated region of the mRNA. EMBO J. 1989, 8:3693-3699.
145. Gunshin H., Allerson C.R., Polycarpou-Schwarz M., Rofts A., Rogers J.T., Kishi F., Hentze M.W., Rouault T.A., Andrews N.C., Hediger M.A. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett. 2001, 509:309-316.
146. Ambros V. microRNAs: tiny regulators with great potential. Cell 2001, 107:823-826.
147. He L., Hannon G.J. MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 2004, 5:522-531.
148. Davis M., Clarke S. Influence of microRNA on the maintenance of human iron metabolism. Nutrients 2013, 5:2611-2628.
149. Zumbrennen-Bullough K.B., Wu Q., Core A.B., Canali S., Chen W., Theurl I., Meynard D., Babitt J.L. MicroRNA-130a is up-regulated in mouse liver by iron deficiency and targets the bone morphogenetic protein (BMP) receptor ALK2 to attenuate BMP signaling and hepcidin transcription. J. Biol. Chem. 2014, 289:23796-23808.
150. Joshi H.P., Subramanian I.V., Schnettler E.K., Ghosh G., Rupaimoole R., Evans C., Saluja M., Jing Y., Cristina I., Roy S., Zeng Y., Shah V.H., Sood A.K., Ramakrishnan S. Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:5331-5336.
151. Asci R., Vallefuoco F., Andolfo I., Bruno M., De Falco L., Iolascon A. Transferrin receptor 2 gene regulation by microRNA 221 in SH-SY5Y cells treated with MPP(+) as Parkinson's disease cellular model. Neurosci. Res. 2013, 77:121-127.
152. Shpyleva S., Pogribna M., Cozart C., Bryant M.S., Muskhelishvili L., Tryndyak V.P., Ross S.A., Beland F.A., Pogribny I.P. Interstrain differences in the progression of nonalcoholic steatohepatitis to fibrosis in mice are associated with altered hepatic iron metabolism. J. Nutr. Biochem. 2014, 25:1235-1242.
153. Weitz S.H., Gong M., Barr I., Weiss S., Guo F. Processing of microRNA primary transcripts requires heme in mammalian cells. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:1861-1866.
154. Li Y., Lin L., Li Z., Ye X., Xiong K., Aryal B., Xu Z., Paroo Z., Liu Q., He C., Jin P. Iron homeostasis regulates the activity of the microRNA pathway through poly(C)-binding protein 2. Cell Metab. 2012, 15:895-904.
155. Seidah N.G., Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat. Rev. Drug Discov. 2012, 11:367-383.
156. Guillemot J., Canuel M., Essalmani R., Prat A., Seidah N.G. Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin. Hepatology 2013, 57:2514-2524.
157. Gagliardo B., Kubat N., Faye A., Jaouen M., Durel B., Deschemin J.C., Canonne-Hergaux F., Sari M.A., Vaulont S. Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process. J. Hepatol. 2009, 50:394-401.
158. Andrews N.C. Disorders of iron metabolism. N. Engl. J. Med. 1999, 341:1986-1995.
159. Deugnier Y., Turlin B. Pathology of hepatic iron overload. World J. Gastroenterol. 2007, 13:4755-4760.
160. Clark S.F. Iron deficiency anemia. Nutr. Clin. Pract. 2008, 23:128-141.
161. Weiss G., Goodnough L.T. Anemia of chronic disease. N. Engl. J. Med. 2005, 352:1011-1023.
162. Beutler E. Iron storage disease: facts, fiction and progress. Blood Cells Mol. Dis. 2007, 39:140-147.
163. Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 2010, 139:393-408. (408 e391-392).
164. Feder J.N., Gnirke A., Thomas W., Tsuchihashi Z., Ruddy D.A., Basava A., Dormishian F., Domingo R., Ellis M.C., Fullan A., Hinton L.M., Jones N.L., Kimmel B.E., Kronmal G.S., Lauer P., Lee V.K., Loeb D.B., Mapa F.A., McClelland E., Meyer N.C., Mintier G.A., Moeller N., Moore T., Morikang E., Prass C.E., Quintana L., Starnes S.M., Schatzman R.C., Brunke K.J., Drayna D.T., Risch N.J., Bacon B.R., Wolff R.K. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 1996, 13:399-408.
165. Roetto A., Papanikolaou G., Politou M., Alberti F., Girelli D., Christakis J., Loukopoulos D., Camaschella C. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat. Genet. 2003, 33:21-22.
166. Papanikolaou G., Samuels M.E., Ludwig E.H., MacDonald M.L., Franchini P.L., Dube M.P., Andres L., MacFarlane J., Sakellaropoulos N., Politou M., Nemeth E., Thompson J., Risler J.K., Zaborowska C., Babakaiff R., Radomski C.C., Pape T.D., Davidas O., Christakis J., Brissot P., Lockitch G., Ganz T., Hayden M.R., Goldberg Y.P. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat. Genet. 2004, 36:77-82.
167. Sham R.L., Phatak P.D., West C., Lee P., Andrews C., Beutler E. Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features. Blood Cells Mol. Dis. 2005, 34:157-161.
168. Camaschella C., Roetto A., Cali A., De Gobbi M., Garozzo G., Carella M., Majorano N., Totaro A., Gasparini P. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat. Genet. 2000, 25:14-15.
169. Adams P.C., Reboussin D.M., Barton J.C., McLaren C.E., Eckfeldt J.H., McLaren G.D., Dawkins F.W., Acton R.T., Harris E.L., Gordeuk V.R., Leiendecker-Foster C., Speechley M., Snively B.M., Holup J.L., Thomson E., Sholinsky P. Hemochromatosis and iron-overload screening in a racially diverse population. N. Engl. J. Med. 2005, 352:1769-1778.
170. Merryweather-Clarke A.T., Pointon J.J., Shearman J.D., Robson K.J. Global prevalence of putative haemochromatosis mutations. J. Med. Genet. 1997, 34:275-278.
171. Feder J.N., Tsuchihashi Z., Irrinki A., Lee V.K., Mapa F.A., Morikang E., Prass C.E., Starnes S.M., Wolff R.K., Parkkila S., Sly W.S., Schatzman R.C. The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J. Biol. Chem. 1997, 272:14025-14028.
172. Lawless M.W., Mankan A.K., White M., O'Dwyer M.J., Norris S. Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmic reticulum stress responses. BMC Cell Biol. 2007, 8:30.
173. Pinto J.P., Ramos P., de Almeida S.F., Oliveira S., Breda L., Michalak M., Porto G., Rivella S., de Sousa M. Protective role of calreticulin in HFE hemochromatosis. Free Radic. Biol. Med. 2008, 44:99-108.
174. Walsh A., Dixon J.L., Ramm G.A., Hewett D.G., Lincoln D.J., Anderson G.J., Subramaniam V.N., Dodemaide J., Cavanaugh J.A., Bassett M.L., Powell L.W. The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis. Clin. Gastroenterol. Hepatol. 2006, 4:1403-1410.
175. Alvarez-Coca-Gonzalez J., Moreno-Carralero M.I., Martinez-Perez J., Mendez M., Garcia-Ros M., Moran-Jimenez M.J. The hereditary hyperferritinemia-cataract syndrome: a family study. Eur. J. Pediatr. 2010, 169:1553-1555.
176. Kono S. Aceruloplasminemia: an update. Int. Rev. Neurobiol. 2013, 110:125-151.
177. Aslan D., Crain K., Beutler E. A new case of human atransferrinemia with a previously undescribed mutation in the transferrin gene. Acta Haematol. 2007, 118:244-247.
178. Beghe C., Wilson A., Ershler W.B. Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature. Am. J. Med. 2004, 116(Suppl. 7A):3S-10S.
179. Haas J.D., Brownlie T.T. Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J. Nutr. 2001, 131:676S-688S. (discussion 688S-690S).
180. Beard J.L. Iron biology in immune function, muscle metabolism and neuronal functioning. J. Nutr. 2001, 131:568S-579S. (discussion 580S).
181. Hartman K.R., Barker J.A. Microcytic anemia with iron malabsorption: an inherited disorder of iron metabolism. Am. J. Hematol. 1996, 51:269-275.
182. Finberg K.E., Heeney M.M., Campagna D.R., Aydinok Y., Pearson H.A., Hartman K.R., Mayo M.M., Samuel S.M., Strouse J.J., Markianos K., Andrews N.C., Fleming M.D. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat. Genet. 2008, 40:569-571.
183. Castoldi M., Vujic Spasic M., Altamura S., Elmen J., Lindow M., Kiss J., Stolte J., Sparla R., D'Alessandro L.A., Klingmuller U., Fleming R.E., Longerich T., Grone H.J., Benes V., Kauppinen S., Hentze M.W., Muckenthaler M.U. The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice. J. Clin. Invest. 2011, 121:1386-1396.
184. Schaar D.G., Medina D.J., Moore D.F., Strair R.K., Ting Y. miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation. Exp. Hematol. 2009, 37:245-255.
185. Yoshioka Y., Kosaka N., Ochiya T., Kato T. Micromanaging Iron Homeostasis: hypoxia-inducible micro-RNA-210 suppresses iron homeostasis-related proteins. J. Biol. Chem. 2012, 287:34110-34119.
186. Liao Y., Du X., Lonnerdal B. miR-214 regulates lactoferrin expression and pro-apoptotic function in mammary epithelial cells. J. Nutr. 2010, 140:1552-1556.
187. Liao Y., Lonnerdal B. miR-584 mediates post-transcriptional expression of lactoferrin receptor in Caco-2 cells and in mouse small intestine during the perinatal period. Int. J. Biochem. Cell Biol. 2010, 42:1363-1369.
188. Andolfo I., De Falco L., Asci R., Russo R., Colucci S., Gorrese M., Zollo M., Iolascon A. Regulation of divalent metal transporter 1 (DMT1) non-IRE isoform by the microRNA Let-7d in erythroid cells. Haematologica 2010, 95:1244-1252.
189. Hou W., Tian Q., Steuerwald N.M., Schrum L.W., Bonkovsky H.L. The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes. Biochim. Biophys. Acta 2012, 1819:1113-1122.
190. Hou W., Tian Q., Zheng J., Bonkovsky H.L. MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins. Hepatology 2010, 51:1494-1504.
191. Shpyleva S.I., Tryndyak V.P., Kovalchuk O., Starlard-Davenport A., Chekhun V.F., Beland F.A., Pogribny I.P. Role of ferritin alterations in human breast cancer cells. Breast Cancer Res. Treat. 2011, 126:63-71.
192. Sangokoya C., Doss J.F., Chi J.T. Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin. PLoS Genet. 2013, 9:e1003408.