Expression of iron homeostasis proteins in the spinal cord in experimental autoimmune encephalomyelitis and their implications for iron accumulation

Neurobiology of Disease

Volumn 81, Issue , 2015, Pages 93-107

  Zarruk, Juan G ^a   Berard, Jennifer L ^a   Passos dos Santos, Rosmarini ^a   Kroner, Antje ^a   Lee, Jaekwon ^b   Arosio, Paolo ^c   David, Samuel ^a  

^a RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b UNIVERSITY OF NEBRASKA LINCOLN   (United States)

^c UNIVERSITY OF BRESCIA   (Italy)

Author keywords

Ceruloplasmin; Experimental autoimmune encephalomyelitis; Ferroportin; Hepcidin; Iron; Iron efflux; Iron influx; Macrophage; Microglia; MS

Indexed keywords

CD71 ANTIGEN; CERULOPLASMIN; HEPCIDIN; HEPHAESTIN; IRON; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; UNCLASSIFIED DRUG; ZINC TRANSPORTER; ZRT IRT LIKE PROTEIN 14; CATION TRANSPORT PROTEIN; CD11B ANTIGEN; FERRITIN; FREUND ADJUVANT; GLIAL FIBRILLARY ACIDIC PROTEIN; HEPH PROTEIN, MOUSE; MEMBRANE PROTEIN; METAL TRANSPORTING PROTEIN 1; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; MYELIN OLIGODENDROCYTE GLYCOPROTEIN (35-55); NERVE PROTEIN; PEPTIDE FRAGMENT; SOLUTE CARRIER FAMILY 11- (PROTON-COUPLED DIVALENT METAL ION TRANSPORTERS), MEMBER 2; TFRC PROTEIN, MOUSE; TPPP PROTEIN, MOUSE; TRANSFERRIN RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CONTROLLED STUDY; DISEASE COURSE; DISEASE DURATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FEMALE; IRON METABOLISM; IRON STORAGE; IRON TRANSPORT; MACROPHAGE; MOUSE; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; ANIMAL; C57BL MOUSE; CHEMICALLY INDUCED; COMPLICATION; DISEASE MODEL; GENETICS; IRON METABOLISM DISORDERS; METABOLISM; MITOCHONDRION; PATHOLOGY; SPINAL CORD; TIME FACTOR; ULTRASTRUCTURE;

ANIMALS; ANTIGENS, CD11B; CATION TRANSPORT PROTEINS; CERULOPLASMIN; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; FERRITINS; FREUND'S ADJUVANT; GLIAL FIBRILLARY ACIDIC PROTEIN; HEPCIDINS; IRON; IRON METABOLISM DISORDERS; MEMBRANE PROTEINS; MICE; MICE, INBRED C57BL; MITOCHONDRIA; MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; NERVE TISSUE PROTEINS; PEPTIDE FRAGMENTS; RECEPTORS, TRANSFERRIN; SPINAL CORD; TIME FACTORS;

EID: 84935903463     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2015.02.001     Document Type: Article

References (64)

1. Arosio P., Levi S. Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim. Biophys. Acta 2010, 1800:783-792.
2. Bagnato F., Hametner S., Yao B., van Gelderen P., Merkle H., Cantor F.K., Lassmann H., Duyn J.H. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain 2011, 134:3602-3615.
3. Bakshi R., Benedict R.H., Bermel R.A., Caruthers S.D., Puli S.R., Tjoa C.W., Fabiano A.J., Jacobs L. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch. Neurol. 2002, 59:62-68.
4. Berard J.L., Wolak K., Fournier S., David S. Characterization of relapsing-remitting and chronic forms of experimental autoimmune encephalomyelitis in C57BL/6 mice. Glia 2010, 58:434-445.
5. Campbell G.R., Ziabreva I., Reeve A.K., Krishnan K.J., Reynolds R., Howell O., Lassmann H., Turnbull D.M., Mahad D.J. Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann. Neurol. 2011, 69:481-492.
6. Connor J.R., Menzies S.L. Relationship of iron to oligodendrocytes and myelination. Glia 1996, 17:83-93.
7. Connor J.R., Menzies S.L., Burdo J.R., Boyer P.J. Iron and iron management proteins in neurobiology. Pediatr. Neurol. 2001, 25:118-129.
8. Craelius W., Migdal M.W., Luessenhop C.P., Sugar A., Mihalakis I. Iron deposits surrounding multiple sclerosis plaques. Arch. Pathol. Lab. Med. 1982, 106:397-399.
9. Donovan A., Lima C.A., Pinkus J.L., Pinkus G.S., Zon L.I., Robine S., Andrews N.C. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 2005, 1:191-200.
10. Drysdale J., Arosio P., Invernizzi R., Cazzola M., Volz A., Corsi B., Biasiotto G., Levi S. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol. Dis. 2002, 29:376-383.
11. Fischer M.T., Sharma R., Lim J.L., Haider L., Frischer J.M., Drexhage J., Mahad D., Bradl M., van Horssen J., Lassmann H. NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain 2012, 135:886-899.
12. Forge J.K., Pedchenko T.V., LeVine S.M. Iron deposits in the central nervous system of SJL mice with experimental allergic encephalomyelitis. Life Sci. 1998, 63:2271-2284.
13. Garrick M.D., Dolan K.G., Horbinski C., Ghio A.J., Higgins D., Porubcin M., Moore E.G., Hainsworth L.N., Umbreit J.N., Conrad M.E., Feng L., Lis A., Roth J.A., Singleton S., Garrick L.M. DMT1: a mammalian transporter for multiple metals. Biometals 2003, 16:41-54.
14. Hadziahmetovic M., Dentchev T., Song Y., Haddad N., He X., Hahn P., Pratico D., Wen R., Harris Z.L., Lambris J.D., Beard J., Dunaief J.L. Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD. Invest. Ophthalmol. Vis. Sci. 2008, 49:2728-2736.
15. Haider L., Simeonidou C., Steinberger G., Hametner S., Grigoriadis N., Deretzi G., Kovacs G.G., Kutzelnigg A., Lassmann H., Frischer J.M. Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron. J. Neurol. Neurosurg. Psychiatry 2014, 85:1386-1395.
16. Hametner S., Wimmer I., Haider L., Pfeifenbring S., Bruck W., Lassmann H. Iron and neurodegeneration in the multiple sclerosis brain. Ann. Neurol. 2013, 74:848-861.
17. Höftberger R., Fink S., Aboul-Enein F., Botond G., Olah J., Berki T., Ovadi J., Lassmann H., Budka H., Kovacs G.G. Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis. Glia 2010, 58:1847-1857.
18. Jeong S.Y., David S. Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. J. Biol. Chem. 2003, 278:27144-27148.
19. Jeong S.Y., David S. Age-related changes in iron homeostasis and cell death in the cerebellum of ceruloplasmin-deficient mice. J. Neurosci. Off. J. Soc. Neurosci. 2006, 26:9810-9819.
20. Jeong S.Y., Rathore K.I., Schulz K., Ponka P., Arosio P., David S. Dysregulation of iron homeostasis in the CNS contributes to disease progression in a mouse model of amyotrophic lateral sclerosis. J. Neurosci. Off. J. Soc. Neurosci. 2009, 29:610-619.
21. Kalyvas A., David S. Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease. Neuron 2004, 41:323-335.
22. Kroner A., Greenhalgh A.D., Zarruk J.G., Passos dos Santos R., Gaestel M., David S. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron 2014, 83:1098-1116.
23. Lassmann H. Mechanisms of white matter damage in multiple sclerosis. Glia 2014, 62:1816-1830.
24. Lassmann H., van Horssen J., Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat. Rev. Neurol. 2012, 8:647-656.
25. Lawen A., Lane D.J. Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid. Redox Signal. 2013, 18:2473-2507.
26. 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.
27. LeVine S.M., Maiti S., Emerson M.R., Pedchenko T.V. Apoferritin attenuates experimental allergic encephalomyelitis in SJL mice. Dev. Neurosci. 2002, 24:177-183.
28. 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.
29. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25:402-408.
30. Mahad D., Lassmann H., Turnbull D. Review: mitochondria and disease progression in multiple sclerosis. Neuropathol. Appl. Neurobiol. 2008, 34:577-589.
31. Mahad D., Ziabreva I., Lassmann H., Turnbull D. Mitochondrial defects in acute multiple sclerosis lesions. Brain 2008, 131:1722-1735.
32. Mahad D.J., Ziabreva I., Campbell G., Lax N., White K., Hanson P.S., Lassmann H., Turnbull D.M. Mitochondrial changes within axons in multiple sclerosis. Brain 2009, 132:1161-1174.
33. McCarthy R.C., Kosman D.J. Ferroportin and exocytoplasmic ferroxidase activity are required for brain microvascular endothelial cell iron efflux. J. Biol. Chem. 2013, 288:17932-17940.
34. McCarthy R.C., Kosman D.J. Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells. PLoS One 2014, 9:e89003.
35. Meguro R., Asano Y., Odagiri S., Li C., Iwatsuki H., Shoumura K. Nonheme-iron histochemistry for light and electron microscopy: a historical, theoretical and technical review. Arch. Histol. Cytol. 2007, 70:1-19.
36. Mehta V., Pei W., Yang G., Li S., Swamy E., Boster A., Schmalbrock P., Pitt D. Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions. PLoS One 2013, 8:e57573.
37. Mitchell K.M., Dotson A.L., Cool K.M., Chakrabarty A., Benedict S.H., LeVine S.M. Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis. Mult. Scler. 2007, 13:1118-1126.
38. Mittal B., Doroudchi M.M., Jeong S.Y., Patel B.N., David S. Expression of a membrane-bound form of the ferroxidase ceruloplasmin by leptomeningeal cells. Glia 2003, 41:337-346.
39. Nam H., Wang C.Y., Zhang L., Zhang W., Hojyo S., Fukada T., Knutson M.D. ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders. Haematologica 2013, 98:1049-1057.
40. Nathoo N., Agrawal S., Wu Y., Haylock-Jacobs S., Yong V.W., Foniok T., Barnes S., Obenaus A., Dunn J.F. Susceptibility-weighted imaging in the experimental autoimmune encephalomyelitis model of multiple sclerosis indicates elevated deoxyhemoglobin, iron deposition and demyelination. Mult. Scler. 2013, 19:721-731.
41. Nedergaard M., Ransom B., Goldman S.A. New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci. 2003, 26:523-530.
42. Neema M., Arora A., Healy B.C., Guss Z.D., Brass S.D., Duan Y., Buckle G.J., Glanz B.I., Stazzone L., Khoury S.J., Weiner H.L., Guttmann C.R., Bakshi R. Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis. J. Neuroimaging 2009, 19:3-8.
43. 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.
44. 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.
45. Pandolfo M. Iron metabolism and mitochondrial abnormalities in Friedreich ataxia. Blood Cells Mol. Dis. 2002, 29:536-547. (discussion 548-552).
46. Patel B.N., Dunn R.J., Jeong S.Y., Zhu Q., Julien J.P., David S. Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. J. Neurosci. Off. J. Soc. Neurosci. 2002, 22:6578-6586.
47. Pedchenko T.V., LeVine S.M. Desferrioxamine suppresses experimental allergic encephalomyelitis induced by MBP in SJL mice. J. Neuroimmunol. 1998, 84:188-197.
48. Ponka P., Lok C.N. The transferrin receptor: role in health and disease. Int. J. Biochem. Cell Biol. 1999, 31:1111-1137.
49. Rathore K.I., Kerr B.J., Redensek A., Lopez-Vales R., Jeong S.Y., Ponka P., David S. Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage. J. Neurosci. Off. J. Soc. Neurosci. 2008, 28:12736-12747.
50. Rouault T.A. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat. Chem. Biol. 2006, 2:406-414.
51. Rouault T.A., Tong W.H. Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat. Rev. Mol. Cell Biol. 2005, 6:345-351.
52. Schonberg D.L., Goldstein E.Z., Sahinkaya F.R., Wei P., Popovich P.G., McTigue D.M. Ferritin stimulates oligodendrocyte genesis in the adult spinal cord and can be transferred from macrophages to NG2 cells in vivo. J. Neurosci. Off. J. Soc. Neurosci. 2012, 32:5374-5384.
53. Schuh C., Wimmer I., Hametner S., Haider L., Van Dam A.M., Liblau R.S., Smith K.J., Probert L., Binder C.J., Bauer J., Bradl M., Mahad D., Lassmann H. Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models. Acta Neuropathol. 2014, 128:247-266.
54. Schulz K., Vulpe C.D., Harris L.Z., David S. Iron efflux from oligodendrocytes is differentially regulated in gray and white matter. J. Neurosci. Off. J. Soc. Neurosci. 2011, 31:13301-13311.
55. Schulz K., Kroner A., David S. Iron efflux from astrocytes plays a role in remyelination. J. Neurosci. Off. J. Soc. Neurosci. 2012, 32:4841-4847.
56. Sindrilaru A., Peters T., Wieschalka S., Baican C., Baican A., Peter H., Hainzl A., Schatz S., Qi Y., Schlecht A., Weiss J.M., Wlaschek M., Sunderkotter C., Scharffetter-Kochanek K. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J. Clin. Invest. 2011, 121:985-997.
57. Singh N., Haldar S., Tripathi A.K., Horback K., Wong J., Sharma D., Beserra A., Suda S., Anbalagan C., Dev S., Mukhopadhyay C.K., Singh A. Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid. Redox Signal. 2014, 20:1324-1363.
58. Snyder A.M., Wang X., Patton S.M., Arosio P., Levi S., Earley C.J., Allen R.P., Connor J.R. Mitochondrial ferritin in the substantia nigra in restless legs syndrome. J. Neuropathol. Exp. Neurol. 2009, 68:1193-1199.
59. Stephenson E., Nathoo N., Mahjoub Y., Dunn J.F., Yong V.W. Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat. Rev. Neurol. 2014, 10:459-468.
60. Theil E.C. Ferritin: the protein nanocage and iron biomineral in health and in disease. Inorg. Chem. 2013, 52:12223-12233.
61. Todorich B., Pasquini J.M., Garcia C.I., Paez P.M., Connor J.R. Oligodendrocytes and myelination: the role of iron. Glia 2009, 57:467-478.
62. Vulpe C.D., Kuo Y.M., Murphy T.L., Cowley L., Askwith C., Libina N., Gitschier J., Anderson G.J. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat. Genet. 1999, 21:195-199.
63. Witte M.E., Mahad D.J., Lassmann H., van Horssen J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol. Med. 2014, 20:179-187.
64. Zecca L., Youdim M.B., Riederer P., Connor J.R., Crichton R.R. Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci. 2004, 5:863-873.