An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

eLife

Volumn 5, Issue NOVEMBER2016, 2016, Pages

  Lakhal Littleton, Samira ^a   Wolna, Magda ^a   Chung, Yu Jin ^a   Christian, Helen C ^a   Heather, Lisa C ^a   Brescia, Marcella ^a   Ball, Vicky ^a   Diaz, Rebeca ^b   Santos, Ana ^b   Biggs, Daniel ^b   Clarke, Kieran ^a   Davies, Benjamin ^b   Robbins, Peter A ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACONITATE HYDRATASE; FERRITIN; FERROPORTIN; HEMOGLOBIN; HEPCIDIN; IRON; MULTIENZYME COMPLEX; CATION TRANSPORT PROTEIN; METAL TRANSPORTING PROTEIN 1;

ADULT; ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDIAC MUSCLE CELL; CINE MAGNETIC RESONANCE IMAGING; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GENE DELETION; GENE EXPRESSION; HEART; HEART FUNCTION; HEART PERFORMANCE; HEART VENTRICLE EJECTION; HOMEOSTASIS; IMMUNOHISTOCHEMISTRY; IRON DEFICIENCY; IRON HOMEOSTASIS; MALE; MOUSE; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; SURVIVAL; TRANSMISSION ELECTRON MICROSCOPY; UPREGULATION; ANIMAL; GENE INACTIVATION; GENE TARGETING; GENETICS; METABOLISM;

ANIMALS; CATION TRANSPORT PROTEINS; GENE KNOCK-IN TECHNIQUES; GENE KNOCKOUT TECHNIQUES; HEPCIDINS; HOMEOSTASIS; IRON; MICE; MYOCYTES, CARDIAC;

EID: 85006930176     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.19804     Document Type: Article

References (57)

1. Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ. 2001. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. European Heart Journal 22:2171-2179. doi:10.1053/euhj.2001.2822,PMID:11913479
2. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lu¨ scher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P, FAIR-HF Trial Investigators. 2009. Ferric carboxymaltose in patients with heart failure and iron deficiency. New England Journal of Medicine 361:2436-2448. doi:10.1056/NEJMoa0908355,PMID:19920054
3. Ashrafian H, Frenneaux MP, Opie LH. 2007. Metabolic mechanisms in heart failure. Circulation 116:434-448. doi:10.1161/CIRCULATIONAHA.107.702795,PMID:17646594
4. Avni T, Leibovici L, Gafter-Gvili A. 2012. Iron supplementation for the treatment of chronic heart failure and iron deficiency: systematic review and meta-analysis. European Journal of Heart Failure 14:423-429. doi:10.1093/eurjhf/hfs017,PMID:22348897
5. Bastin J, Drakesmith H, Rees M, Sargent I, Townsend A. 2006. Localisation of proteins of iron metabolism in the human placenta and liver. British Journal of Haematology 134:532-543. doi:10.1111/j.1365-2141.2006.06216.x,PMID:16856887
6. Beaubien G, Schäfer MK, Weihe E, Dong W, Chrétien M, Seidah NG, Day R. 1995. The distinct gene expression of the pro-hormone convertases in the rat heart suggests potential substrates. Cell & Tissue Research 279:539-549. doi:10.1007/BF00318166,PMID:7736551
7. Belke DD, Larsen TS, Gibbs EM, Severson DL. 2000. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. American Journal of Physiology Endocrinology and Metabolism 279:E1104-E1113. PMID: 11052966
8. Brooks KJ, Hargreaves IP, Bates TE. 2000. Nitric-oxide-induced inhibition of mitochondrial complexes following aglycaemic hypoxia in neonatal cortical rat brain slices. Developmental Neuroscience 22:359-365. doi:10.1159/000017461,PMID:11111151
9. Camaschella C. 2005. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106:3710-3717. doi:10.1182/blood-2005-05-1857,PMID:16030190
10. Comín-Colet J, Enjuanes C, González G, Torrens A, Cladellas M, Meroño O, Ribas N, Ruiz S, Gómez M, Verdú JM, Bruguera J. 2013. Iron deficiency is a key determinant of health-related quality of life in patients with chronic heart failure regardless of anaemia status. European Journal of Heart Failure 15:1164-1172. doi:10.1093/eurjhf/hft083,PMID:23703106
11. Dallman PR. 1986. Biochemical basis for the manifestations of iron deficiency. Annual Review of Nutrition 6:13-40. doi:10.1146/annurev.nu.06.070186.000305,PMID:3524613
12. De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, Gouya L, Camaschella C, Beaumont C. 2013. Iron refractory iron deficiency anemia. Haematologica 98:845-853. doi:10.3324/haematol.2012.075515,PMID:23729726
13. Dhur A, Galan P, Hercberg S. 1989. Effects of different degrees of iron deficiency on cytochrome P450 complex and pentose phosphate pathway dehydrogenases in the rat. Journal of Nutrition 119:40-47. PMID: 2492336
14. Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC. 2005. The iron exporter ferroportin/ Slc40a1 is essential for iron homeostasis. Cell Metabolism 1:191-200. doi:10.1016/j.cmet.2005.01.003,PMID:16054062
15. Drakesmith H, Schimanski LM, Ormerod E, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR. 2005. Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 106:1092-1097. doi:10.1182/blood-2005-02-0561,PMID:15831700
16. Evans P, Cindrova-Davies T, Muttukrishna S, Burton GJ, Porter J, Jauniaux E. 2011. Hepcidin and iron species distribution inside the first-trimester human gestational sac. Molecular Human Reproduction 17:227-232. doi:10.1093/molehr/gaq101,PMID:21177636
17. Ezekowitz JA, McAlister FA, Armstrong PW. 2003. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation 107:223-225. doi:10.1161/01.CIR.0000052622.51963.FC,PMID:12538418
18. Ganz T. 2005. Cellular iron: ferroportin is the only way out. Cell Metabolism 1:155-157. doi:10.1016/j.cmet.2005.02.005,PMID:16054057
19. Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, Frishman WH. 2014. Cardiac involvement in hemochromatosis. Cardiology in Review 22:56-68. doi:10.1097/CRD.0b013e3182a67805,PMID:24503941
20. Ichiki T, Boerrigter G, Huntley BK, Sangaralingham SJ, McKie PM, Harty GJ, Harders GE, Burnett JC. 2013. Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis. AJP: Regulatory, Integrative and Comparative Physiology 304:R102-R109. doi:10.1152/ajpregu.00233.2012
21. Jankowska EA, Kasztura M, Sokolski M, Bronisz M, Nawrocka S, Oleśkowska-Florek W, Zymliński R, Biegus J, Siwołowski P, Banasiak W, Anker SD, Filippatos G, Cleland JG, Ponikowski P. 2014. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. European Heart Journal 35:2468-2476. doi:10.1093/eurheartj/ehu235,PMID:24927731
22. Kakinuma Y, Miyauchi T, Yuki K, Murakoshi N, Goto K, Yamaguchi I. 2000. Mitochondrial dysfunction of cardiomyocytes causing impairment of cellular energy metabolism induces apoptosis, and concomitant increase in cardiac endothelin-1 expression. Journal of Cardiovascular Pharmacology 36:S201-204. doi:10.1097/00005344-200036051-00061,PMID:11078377
23. Kato T, Niizuma S, Inuzuka Y, Kawashima T, Okuda J, Tamaki Y, Iwanaga Y, Narazaki M, Matsuda T, Soga T, Kita T, Kimura T, Shioi T. 2010. Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circulation: Heart Failure 3:420-430. doi:10.1161/CIRCHEARTFAILURE.109.888479,PMID:20176713
24. Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA. 2013. Iron deficiency in chronic heart failure: an international pooled analysis. American Heart Journal 165:575-582. doi:10.1016/j.ahj.2013.01.017,PMID:23537975
25. Kulaksiz H, Theilig F, Bachmann S, Gehrke SG, Rost D, Janetzko A, Cetin Y, Stremmel W. 2005. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. Journal of Endocrinology 184:361-370. doi:10.1677/joe.1.05729,PMID:15684344
26. Lakhal-Littleton S, Wolna M, Carr CA, Miller JJ, Christian HC, Ball V, Santos A, Diaz R, Biggs D, Stillion R, Holdship P, Larner F, Tyler DJ, Clarke K, Davies B, Robbins PA. 2015. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function. Proceedings of the National Academy of Sciences 112:3164-3169. doi:10.1073/pnas.1422373112,PMID:25713362
27. Liu P, Jenkins NA, Copeland NG. 2003. A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Research 13:476-484. doi:10.1101/gr.749203,PMID:12618378
28. McCarthy RC, Kosman DJ. 2014. Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells. PLoS One 9:e89003. doi:10.1371/journal.pone.0089003,PMID:24533165
29. McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, Miret S, Bomford A, Peters TJ, Farzaneh F, Hediger MA, Hentze MW, Simpson RJ. 2000. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Molecular Cell 5:299-309. doi:10.1016/S1097-2765(00)80425-6,PMID:10882071
30. Merle U, Fein E, Gehrke SG, Stremmel W, Kulaksiz H. 2007. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology 148:2663-2668. doi:10.1210/en.2006-1331,PMID:17363462
31. Meyer J. 2008. Iron-sulfur protein folds, iron-sulfur chemistry, and evolution. JBIC Journal of Biological Inorganic Chemistry 13:157-170. doi:10.1007/s00775-007-0318-7,PMID:17992543
32. Moos T, Rosengren Nielsen T. 2006. Ferroportin in the postnatal rat brain: implications for axonal transport and neuronal export of iron. Seminars in Pediatric Neurology 13:149-157. doi:10.1016/j.spen.2006.08.003,PMID:17101453
33. Musallam KM, Cappellini MD, Wood JC, Taher AT. 2012. Iron overload in non-transfusion-dependent thalassemia: a clinical perspective. Blood Reviews 26 Suppl 1:S16-19. doi:10.1016/S0268-960X(12)70006-1,PMID:22631036
34. Nanas JN, Matsouka C, Karageorgopoulos D, Leonti A, Tsolakis E, Drakos SG, Tsagalou EP, Maroulidis GD, Alexopoulos GP, Kanakakis JE, Anastasiou-Nana MI. 2006. Etiology of anemia in patients with advanced heart failure. Journal of the American College of Cardiology 48:2485-2489. doi:10.1016/j.jacc.2006.08.034,PMID:17174186
35. Nemeth E, Ganz T. 2014. Anemia of inflammation. Hematology/Oncology Clinics of North America 28:671-681. doi:10.1016/j.hoc.2014.04.005,PMID:25064707
36. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090-2093. doi:10.1126/science.1104742,PMID:15514116
37. Noetzli LJ, Carson SM, Nord AS, Coates TD, Wood JC. 2008. Longitudinal analysis of heart and liver iron in thalassemia major. Blood 112:2973-2978. doi:10.1182/blood-2008-04-148767,PMID:18650452
38. Oexle H, Gnaiger E, Weiss G. 1999. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation. Biochimica Et Biophysica Acta (BBA)-Bioenergetics 1413:99-107. doi:10.1016/S0005-2728(99)00088-2,PMID:10556622
39. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh T, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD, CONFIRM-HF Investigators. 2015. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. European Heart Journal 36:657-668. doi:10.1093/eurheartj/ehu385,PMID:25176939
40. Qiao B, Sugianto P, Fung E, Del-Castillo-Rueda A, Moran-Jimenez MJ, Ganz T, Nemeth E. 2012. Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination. Cell Metabolism 15:918-924. doi:10.1016/j.cmet.2012.03.018,PMID:22682227
41. Rouault T, Klausner R. 1997. Regulation of iron metabolism in eukaryotes. Current Topics in Cellular Regulation 35:1-19. doi:10.1016/s0070-2137(97)80001-5,PMID:9192174
42. Rouault TA. 2006. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nature Chemical Biology 2:406-414. doi:10.1038/nchembio807,PMID:16850017
43. Rouault TA. 2013. Iron metabolism in the CNS: implications for neurodegenerative diseases. Nature Reviews Neuroscience 14:551-564. doi:10.1038/nrn3453,PMID:23820773
44. Schimanski LM, Drakesmith H, Merryweather-Clarke AT, Viprakasit V, Edwards JP, Sweetland E, Bastin JM, Cowley D, Chinthammitr Y, Robson KJ, Townsend AR. 2005. In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations. Blood 105:4096-4102. doi:10.1182/blood-2004-11-4502,PMID:15692071
45. Schönekess BO, Allard MF, Henning SL, Wambolt RB, Lopaschuk GD. 1997. Contribution of glycogen and exogenous glucose to glucose metabolism during ischemia in the hypertrophied rat heart. Circulation Research 81:540-549. doi:10.1161/01.RES.81.4.540,PMID:9314835
46. Silvestri L, Pagani A, Camaschella C. 2008. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood 111:924-931. doi:10.1182/blood-2007-07-100677,PMID:17938254
47. Simonis G, Mueller K, Schwarz P, Wiedemann S, Adler G, Strasser RH, Kulaksiz H. 2010. The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction. Peptides 31:1786-1790. doi:10.1016/j.peptides.2010.05.013,PMID:20553779
48. Solomon EI, Decker A, Lehnert N. 2003. Non-heme iron enzymes: contrasts to heme catalysis. PNAS 100:3589-3594. doi:10.1073/pnas.0336792100,PMID:12598659
49. Sono M, Roach MP, Coulter ED, Dawson JH. 1996. Heme-containing oxygenases. Chemical Reviews 96:2841-2888. doi:10.1021/cr9500500,PMID:11848843
50. Suzuki H, Toba K, Kato K, Ozawa T, Tomosugi N, Higuchi M, Kusuyama T, Iso Y, Kobayashi N, Yokoyama S, Fukuda N, Saitoh H, Akazawa K, Aizawa Y. 2009. Serum hepcidin-20 is elevated during the acute phase of myocardial infarction. The Tohoku Journal of Experimental Medicine 218:93-98. doi:10.1620/tjem.218.93,PMID:19478464
51. Tanne Z, Coleman R, Nahir M, Shomrat D, Finberg JP, Youdim MB. 1994. Ultrastructural and cytochemical changes in the heart of iron-deficient rats. Biochemical Pharmacology 47:1759-1766. doi:10.1016/0006-2952(94)90303-4,PMID:8204092
52. Valore EV, Ganz T. 2008. Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin. Blood Cells, Molecules, and Diseases 40:132-138. doi:10.1016/j.bcmd.2007.07.009
53. Walter PB, Knutson MD, Paler-Martinez A, Lee S, Xu Y, Viteri FE, Ames BN. 2002. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. PNAS 99:2264-2269. doi:10.1073/pnas.261708798,PMID:11854522
54. Ward DM, Kaplan J. 2012. Ferroportin-mediated iron transport: expression and regulation. Biochimica Et Biophysica Acta 1823:1426-1433. doi:10.1016/j.bbamcr.2012.03.004,PMID:22440327
55. Wolff NA, Liu W, Fenton RA, Lee WK, Thévenod F, Smith CP. 2011. Ferroportin 1 is expressed basolaterally in rat kidney proximal tubule cells and iron excess increases its membrane trafficking. Journal of Cellular and Molecular Medicine 15:209-219. doi:10.1111/j.1582-4934.2009.00985.x,PMID:20015204
56. Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. 2015. Lethal cardiomyopathy in mice lacking transferrin receptor in the heart. Cell Reports 13:533-545. doi:10.1016/j.celrep.2015.09.023,PMID:26456827
57. Zhang L, Lu D, Zhang W, Quan X, Dong W, Xu Y, Zhang L. 2012. Cardioprotection by Hepc1 in cTnT(R141W) transgenic mice. Transgenic Research 21:867-878. doi:10.1007/s11248-011-9582-y,PMID:22198484