Proteínas relacionadas con el metabolismo del hierro corporal
DOI:
https://doi.org/10.17533/udea.penh.v18n1a08Palabras clave:
hierro, proteínas de unión al hierro, expresión génica, oxidación-reducción, homeostasis, deficiencia de hierroResumen
Antecedentes: el hierro es uno de los minerales más estudiados; existe amplia información en cuanto a su metabolismo, función, interacciones y regulación; sin embargo, los estudios y análisis realizados se basan en proteínas específicas y pocos integran, en un solo texto, las características de estas moléculas relacionadas con el metabolismo del hierro corporal. Objetivo: profundizar en los aspectos moleculares, metabólicos y de modulación de las proteínas que participan en la homeostasis del hierro y en sus interacciones. Materiales y métodos: se hizo una búsqueda sistemática de información en bases de datos científicas de artículos sobre el tema, publicados entre 2006 y 2016. Resultados: la homeostasis del hierro corporal, es un proceso complejo y altamente regulado por diferentes moléculas que participan de manera integrada en su metabolismo; en los últimos años han surgido nuevas proteínas, algunas de ellas participan en el transporte de otros nutrientes y se les ha encontrado relación con el control humoral y celular del hierro; además, involucran la participación de varios órganos, tejidos y sistemas. Esta revisión incluye proteínas encargadas de facilitar el aprovechamiento biológico del nutriente, así como aquellas que protegen a las células de toxicidad por exceso de este mineral.
Descargas
Citas
Goforth JB, Anderson SA, Nizzi CP, Eisenstein RS. Multiple determinants within iron-responsive elements dictate iron regulatory protein binding and regulatory hierarchy. RNA. 2009;16:154-69.
Campillos M, Cases I, Hentze MW, Sanchez M. SIREs: searching for iron-responsive elements. Nucleic Acids Res. 2010;38:W360-7.
GenBank. Full=Cytoplasmic aconitate hydratase; Short=Aconitase; AltName: Full=Citrate hydro-lyase; AltName: Full=Ferritin repressor protein; AltName: Full=Iron regulatory protein 1; Short=IRP1; AltName: Full=Iron-responsive element-binding protein 1; Short=IRE-BP UniProtKB/Swiss-Prot: Q01059.1 [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/Q01059.1
Kaptain S, Downey WE, Tang C, Philpott A, Haile D, Orloff DG, et al. A regulated RNA binding protein also possesses aconitase activity. Proc Natl Acad Sci. USA. 1991;88:10109-13.
Xu X, Persson HL, Richardson DR. Molecular pharmacology of the interaction of anthracyclines with iron. Mol Pharmacol. 2005;68:261-71.
Phillips JD, Kinikini DV, Yu Y, Guo B, Leibold EA. Differential regulation of IRP1 and IRP2 by nitric oxide in rat hepatoma cells. Blood. 1996;87:2983-92.
Galy B, Ferring-Appel D, Becker C, Gretz N, Gröne H-J, Schümann K, et al. Iron regulatory proteins control a mucosal block to intestinal iron absorption. Cell Rep. 2013;3:844-57.
GenBank. RecName: Full=Iron-responsive element-binding protein 2; Short=IRE-BP 2; AltName: Full=Iron regulatory protein 2; Short=IRP2. UniProtKB/Swiss-Prot: P48200.3. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/P48200.3
MacKenzie EL, Iwasaki K, Tsuji Y. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Signal. 2008;10:997-1030.
Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434:365-81.
Anderson GJ, Vulpe CD. Mammalian iron transport. Cell Mol Life Sci. 2009;66:3241-61.
Piccinelli P, Samuelsson T. Evolution of the iron-responsive element. RNA. 2007;13:952-66.
Linder MC. Mobilization of stored iron in mammals: A review. Nutrients. 2013;5:4022-50.
Montalbetti N, Simonin A, Simonin C, Awale M, Reymond JL, Hediger MA. Discovery and characterization of a novel noncompetitive inhibitor of the divalent metal transporter DMT1/SLC11A2. Biochem Pharmacol. 2015; 96:216-24.
GenBank. RecName: Full=Proton-coupled folate transporter; AltName: Full=G21; AltName: Full=Heme carrier protein 1; Alt-Name: Full=PCFT/HCP1; AltName: Full=Solute carrier family 46 member 1. UniProtKB/Swiss-Prot: Q96NT5.1. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/Q96NT5.1
GenBank. SLC11A2 protein [Homo sapiens]. GenBank: AAH02592.1. 2005. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/AAH02592.1
Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, et al. Identification of an intestinal heme transporter. Cell. 2005;122:789-801.
Gropper S, Smith J. Essential trace and ultratrace minerals. In: Sareen S, ed. Advanced nutrition and human metabolism. 6 ed. Belmont: Wadsworth Cengage Learning; 2013. p. 484-5.
Le Blanc S, Garrick MD, Arredondo M. Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism. Am J Physiol. Cell Physiol. 2012;302:C1780-5.
Khan AA, Quigley JG. Heme and FLVCR-related transporter families SLC48 and SLC49. Mol Aspects Med. 2013;34:669-82.
GenBank. RecName: Full=Heme oxygenase 1; Short=HO-. UniProtKB/Swiss-Prot: P09601.1. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/P09601.1
GenBank. RecName: Full=Heme oxygenase 2; Short=HO-2. UniProtKB/Swiss-Prot: P30519.2. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/P30519.2
West AR, Oates PS. Mechanisms of heme iron absorption: Current questions and controversies. World J Gastroenterol. 2008;14:4101-10.
Ayuso P, Agúndez JAG, Alonso-Navarro H, Martínez C, Benito-León J, Ortega-Cubero S, et al. Heme oxygenase 1 and 2 common genetic variants and risk for essential tremor. Medicine. 2015;94:e968.
Doré S, Sampei K, Goto S, Alkayed NJ, Guastella D, Blackshaw S, et al. Heme oxygenase-2 is neuroprotective in cerebral ischemia. Mol Med. 1999;5:656-63.
Ma B, Day JP, Phillips H, Slootsky B, Tolosano E, Doré S. Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage. J Neuroinflammation. 2016;13:26.
Garrick MD. Human iron transporters. Genes Nutr. 2011;6:45-54.
Mackenzie B, Takanaga H, Hubert N, Rolfs A, Hediger MA. Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1). Biochem J. 2007;403:59-69.
Kühn LC. Iron regulatory proteins and their role in controlling iron metabolism. Metallomics. 2015;7:232-43.
Camaschella C, Pagani A. Iron and erythropoiesis: a dual relationship. Int J Hematol. 2011;93:21-6.
Iolascon A, Camaschella C, Pospisilova D, Piscopo C, Tchernia G, Beaumont C. Natural history of recessive inheritance of DMT1 mutations. J Pediatr. 2008;152:136-9.
GenBank. transferrin [Homo sapiens]. GenBank: ABI97197.1. 2006. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/ABI97197.1
Gkouvatsos K, Papanikolaou G, Pantopoulos K. Regulation of iron transport and the role of transferrin. Biochim Biophys Acta. 2011;188-202.
Byrne CD. Fatty liver: role of inflammation and fatty acid nutrition. Prostaglandins Leukot Essent Fat Acids. 2010;82:265-71.
Yang R, Zhou Z, Sun G, Gao Y, Xu J. Ferritin, a novel vehicle for iron supplementation and food nutritional factors encapsulation. Trends Food Sci Technol. 2015;44:189-200.
Li L, Fang CJ, Ryan JC, Niemi EC, Lebron JA, Bjorkman PJ, et al. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc Natl Acad Sci. 2010;107:3505-10.
Arosio P, Levi S. Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta. 2010;1800:783-92.
Wachter A. Gene regulation by structured mRNA elements. Trends Genet. 2014;30:172-81.
Aydemir F, Jenkitkasemwong S, Gulec S, Knutson MD. Iron loading increases ferroportin heterogeneous nuclear RNA and mRNA levels in murine J774 macrophages. J Nutr. 2009;139:434-8.
Rochette L, Gudjoncik A, Guenancia C, Zeller M, Cottin Y, Vergely C. The iron-regulatory hormone hepcidin: A possible therapeutic target? Pharmacol. Ther. 2015;146:35-52.
Watt RK. The many faces of the octahedral ferritin protein. Biometals. 2011;24:489-500.
Girelli D, Corrocher R, Bisceglia L, Olivieri O, De Franceschi L, Zelante L, et al. 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. 1995;86:4050-3.
Lenzhofer M, Schroedl F, Trost A, Kaser-Eichberger A, Wiedemann H, Strohmaier C, et al. Aqueous humor ferritin in hereditary hyperferritinemia cataract syndrome. Optom Vis Sci. 2015;92:S40-7.
GenBank. Full=Transferrin receptor protein 1; Short=TR; Short=TfR; Short=TfR1; Short=Trfr; AltName: Full=T9; AltName: Full=p90; AltName: CD_antigen=CD71; Contains: RecName: Full=Transferrin receptor protein 1, serum form; Short=sTfR.NCBI Reference Sequence: NP_001121620.1 2015. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/NP_001121620.1
Beaumont C, Vaulont S. Iron homeostasis. In: Beaumont C, Beris P, Beuzard Y, Brugnara C, eds. ESH Handbook on disorders of iron metabolism. París: European School of Haematology; 2009. p. 488-511.
Yersin A, Osada T, Ikai A. Exploring transferrin-receptor interactions at the single-molecule level. Biophys J. 2008;94:230-40.
Pagani A, Vieillevoye M, Nai A, Rausa M, Ladli M, Lacombe C, et al. Regulation of cell surface transferrin receptor-2 by irondependent cleavage and release of a soluble form. Haematologica. 2015;100:458-65.
Worthen CA, Enns CA. The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body. Front Pharmacol. 2014;5:34.
GenBank. HFE [Homo sapiens]. GenBank: CAB07442.1. 2008. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/CAB07442.1
Aisen P. Transferrin receptor 1. Int J Biochem Cell Biol. 2004;36:2137-43.
Balesaria S, Hanif R, Salama M, Raja K, Bayele HK, McArdle H, et al. Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron. Haematologica. 2012;97:671-9.
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. Mol. Basis Dis. 2014;1842:2298-305.
GenBank. SLC40A1 solute carrier family 40 (iron-regulated transporter), member 1 [Homo sapiens]. GenBank: CAB07442.12015. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/gene/30061
Rice AE, Mendez MJ, Hokanson CA, Rees DC, Bjorkman PJ. Investigation of the biophysical and cell biological properties of ferroportin, a multipass integral membrane protein iron exporter. J Mol Biol. 2009;386:717-32.
Cianetti L, Gabbianelli M, Sposi NM. Ferroportin and erythroid cells: an update. Adv Hematol. 2010; Article ID 404173. Doi: http://dx.doi.org/10.1155/2010/404173. [citado mayo de 2015]. Disponible en: http://www.hindawi.com/journals/ah/2010/404173/
Liu X-B, Yang F, Haile DJ. Functional consequences of ferroportin 1 mutations. Blood Cells Mol Dis. 2005;35:33-46.
De Domenico I, Ward DM, Musci G, Kaplan J. Evidence for the multimeric structure of ferroportin. Blood. 2007;109:2205-9.
Le Gac G, Ka C, Joubrel R, Gourlaouen I, Lehn P, Mornon J-P, et al. Structure-function analysis of the human ferroportin iron exporter (SLC40A1): Effect of hemochromatosis type 4 disease mutations and identification of critical residues. Hum Mutat. 2013;34:1371-80.
Ward DM, Kaplan J. Ferroportin-mediated iron transport: Expression and regulation. Biochim Biophys Acta. Mol Cell Res. 2012;1823:1426-33.
De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI, et al. The molecular mechanism of hepcidinmediated ferroportin down-regulation. Mol Biol Cell. 2007;18:2569-78.
De Domenico I, Lo E, Ward DM, Kaplan J. Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2. Proc Natl Acad Sci. 2009;106:3800-5.
De Domenico I, Vaughn MB, Li L, Bagley D, Musci G, Ward DM, et al. Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. EMBO J. 2006;25:5396-404.
Ganz T. The role of hepcidin in iron homeostasis. In: Yehuda S, Mostofsky DI, eds. Iron deficiency and overload: from basic biology to clinical medicine. New York: Humana Press; 2010. p. 51-64.
Hintze KJ, McClung JP. Hepcidin: a critical regulator of iron metabolism during hypoxia. Adv Hematol. 2011;2011:1-7.
Li YQ, Bai B, Cao XX, Yan H, Zhuang GH. Ferroportin 1 and hephaestin expression in BeWo cell line with different iron treatment. Cell Biochem Funct. 2012;30:249-55.
Vashchenko G, MacGillivray RTA. Multi-Copper oxidases and human iron metabolism. Nutrients. 2013;5:2289-313.
Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology. Am Soc Hematol Educ Progr. 2006;29-35. [citado mayo de 2015]. Disponible en: http://asheducationbook.hematologylibrary.org/content/2006/1/29.full.pdf+html
Fleming MD. The regulation of hepcidin and its effects on systemic and cellular iron metabolism. Hematology. Am Soc Hematol Educ Progr. 2008;151-8. [citado mayo de 2015]. Disponible en: http://asheducationbook.hematologylibrary.org/content/2008/1/151.long
Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007;18:394-400.
De Domenico I, Ward DM, Kaplan J. Hepcidin and ferroportin: the new players in iron metabolism. Semin Liver Dis. 2011;31:272-9.
Palaneeswari M S, Ganesh M, Karthikeyan T, Devi AJM, Mythili S V. Hepcidin–Minireview. J Clin Diagn Res. 2013;7:1767-71.
Rishi G, Wallace DF, Subramaniam VN. Hepcidin: regulation of the master iron regulator. Biosci Rep. 2015;35:1-12.
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;46:678-84.
Balesaria S, Ramesh B, McArdle H, Bayele HK, Srai SK. Divalent metal-dependent regulation of hepcidin expression by MTF-1. FEBS Lett. 2010;584:719-25.
Przybyszewska J, Zekanowska E. The role of hepcidin, ferroportin, HCP1, and DMT1 protein in iron absorption in the human digestive tract. Prz Gastroenterol. 2014;9:208-13.
Lane DJR, Bae DH, Merlot AM, Sahni S, Richardson DR. Duodenal cytochrome b (DCYTB) in iron metabolism: An update on function and regulation. Nutrients. 2015;7:2274-96.
GenBank. RecName: Full=Hemojuvelin; AltName: Full=Hemochromatosis type 2 protein; AltName: Full=RGM domain family member C; Flags: Precursor UniProtKB/Swiss-Prot: Q6ZVN8. [citado mayo de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/Q6ZVN8.1
Chifman J, Laubenbacher R, Torti S V. A systems biology approach to iron metabolism. In: Corey SJ, Kimmel M, Leonard JN, eds. A systems biology approach to iron metabolism. New York: Springer; 2014. p. 201-25.
Esquivia CM, Acevedo P. Hepcidina: su interacción con la hemojuvelina y su aporte en el diagnóstico de las enfermedades relacionadas con el metabolismo del hierro. Univ. Médica. 2012;53:382-94.
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;8:502-11.
Zhao N, Maxson JE, Zhang RH, Wahedi M, Enns CA, Zhang AS. Neogenin facilitates the induction of hepcidin expression by hemojuvelin in the liver. J Biol Chem. bc.M116.721191. 2016. [citado febrero de 2016]. Disponible en: http://www.jbc.org/content/early/2016/04/12/jbc.M116.721191.long
GenBank. Full=Ceruloplasmin; AltName: Full=Ferroxidase; Flags: Precursor . UniProtKB/Swiss-Prot: P00450.1. 2015. [citado agosto de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/P00450.1
Bento I, Peixoto C, Zaitsev VN, Lindley PF. Ceruloplasmin revisited: structural and functional roles of various metal cationbinding sites. Acta Crystallogr D Biol Crystallogr. 2007;63:240-8.
Maio N, Polticelli F, De Francesco G, Rizzo G, Bonaccorsi di Patti MC, et al. Role of external loops of human ceruloplasmin in copper loading by ATP7B and Ccc2p. J Biol Chem. 2010;285:20507-13.
Miyajima H. Aceruloplasminemia. Neuropathology. 2015;35:83-90.
Das D, Tapryal N, Goswami SK, Fox PL, Mukhopadhyay CK. Regulation of ceruloplasmin in human hepatic cells by redox active copper: identification of a novel AP-1 site in the ceruloplasmin gene. Biochem J. 2007;402:135-41.
Chen H, Attieh ZK, Syed BA, Kuo Y, Stevens V, Fuqua BK, et al. Identification of Zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells. J Nutr. 2010;140:1728-35.
GenBank. hephaestin [Homo sapiens]. GenBank: CAC35365.2. 2008. [citado agosto de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/CAC35365.2
Wessling-Resnick M. Iron imports. III. Transfer of iron from the mucosa into circulation. Am J Physiol Gastrointest Liver Physiol. 2006;290:G1-6.
Anderson GJ, Frazer DM, McKie AT, Vulpe CD. The ceruloplasmin homolog hephaestin and the control of intestinal iron absorption. Blood Cells Mol Dis. 2002;29:367-75.
Chen H, Attieh ZK, Su T, Syed BA, Gao H, Alaeddine RM, et al. Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice. Blood. 2004;103:3933-9.
Yeh KY, Yeh M, Glass J. Interactions between ferroportin and hephaestin in rat enterocytes are reduced after iron ingestion. Gastroenterology. 2011;141:292-9.
GenBank. hephaestin isoform b [Homo sapiens]. NCBI Reference Sequence: NP_055614.1. 2015. [citado agosto de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/NP_055614.1
Prohaska JR. Impact of copper limitation on expression and function of multicopper oxidases (Ferroxidases). Adv Nutr. 2011;2:89-95.
GenBank. feline leukemia virus subgroup C receptor-related protein 1 [Homo sapiens]. NCBI Reference Sequence: NP_054772.1. 2015. [citado agosto de 2015]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/NP_054772.1
Chiabrando D, Vinchi F, Fiorito V, Mercurio S, Tolosano E. Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes. Front Pharmacol. 2014;5:61.
Gozzelino R, Arosio P. Iron homeostasis in health and disease. Int J Mol Sci. 2016;17:130.
GenBank. RecName: Full=Feline leukemia virus subgroup C receptor-related protein 2; AltName: Full=Calcium-chelate transporter; Short=CCT. UniProtKB/Swiss-Prot: Q9UPI3.1 2016. [citado febrero de 2016]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/Q9UPI3.1
GenBank. RecName: Full=Zinc transporter ZIP8; AltName: Full=BCG-induced integral membrane protein in monocyte clone 103 protein; AltName: Full=LIV-1 subfamily of ZIP zinc transporter 6; Short=LZT-Hs6; AltName: Full=Solute carrier family 39 member 8; AltName: Full= UniProtKB/Swiss-Prot: Q9UPI3.1. 2016. [citado febrero de 2016]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/Q9C0K1.1
Gen. RecName: Full=Zinc transporter ZIP14; AltName: Full=Factor for adipocyte differentiation 123; Short=FAD-123; AltName: Full=Solute carrier family 39 member 14; AltName: Full=Zrt- and Irt-like protein 14; Short=ZIP-14; Flags: Precursor. Uni-ProtKB/Swiss-Prot: Q75N73.1. 2016. [citado febrero de 2016]. Disponible en: http://www.ncbi.nlm.nih.gov/protein/Q75N73.1
Jenkitkasemwong S, Wang CY, MacKenzie B, Knutson MD. Physiologic implications of metal-ion transport by ZIP14 and ZIP8. BioMetals. 2012;25:643-55.
Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y. Regulators of Iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci. 2016;41:274-86.
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2024 Universidad de Antioquia