Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice

Proceedings of the National Academy of Sciences of the United States of America

Volumn 105, Issue 33, 2008, Pages 12028-12033

  Ghosh, Manik C ^a   Tong, Wing Hang ^a   Zhang, Deliang ^a   Ollivierre Wilson, Hayden ^a   Singh, Anamika ^a   Krishna, Murali C ^b   Mitchell, James B ^b   Rouault, Tracey A ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Anemia; Axonopathy; Ferritin; Iron sulfur cluster; Transferrin receptor

Indexed keywords

ACONITATE HYDRATASE; CD71 ANTIGEN; EMOXIPIN; FERRITIN; IRON REGULATORY FACTOR; IRON SULFUR PROTEIN; NITROXIDE; PROTEIN SUBUNIT; TEMPOL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DEGENERATIVE DISEASE; DIET; DISEASE ACTIVITY; DISEASE ASSOCIATION; DISEASE COURSE; GENE TARGETING; GENETIC TRANSCRIPTION; HOMEOSTASIS; HUMAN; HUMAN CELL; IRON METABOLISM; IRON RESPONSIVE ELEMENT; MICROCYTIC ANEMIA; MOUSE; NEUROMUSCULAR DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN SYNTHESIS;

ANIMALS; CELL LINE; CYCLIC N-OXIDES; DISEASE PROGRESSION; ENZYME ACTIVATION; HUMANS; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2; MICE; MICE, KNOCKOUT; MOLECULAR STRUCTURE; NEURODEGENERATIVE DISEASES; PROTEIN BINDING; RECEPTORS, TRANSFERRIN; SPIN LABELS;

ANIMALIA; MAMMALIA; MUS;

EID: 50149099153     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0805361105     Document Type: Article

References (36)

1. Rouault TA (2006) The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol 2:406-414.
2. Wallander ML, Leibold EA, Eisenstein RS (2006) Molecular control of vertebrate iron homeostasis by iron regulatory proteins. Biochim Biophys Acta 1763:668-689.
3. Hentze MW, Muckenthaler MU, Andrews NC (2004) Balancing acts: Molecular control of mammalian iron metabolism. Cell 117:285-297.
4. Dupuy J, et al. (2006) Crystal structure of human iron regulatory protein 1 as cytosolic aconitase. Structure 14:129-139.
5. Walden WE, et al. (2006) Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA. Science 314:1903-1908.
6. Meyron-Holtz EG, et al. (2004) Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J 23:386-395.
7. Cooperman SS, et al. (2005) Microcytic anemia, erythropoietic protoporphyria, and neurodegeneration in mice with targeted deletion of iron-regulatory protein 2. Blood 106:1084-1091.
8. Galy B, et al. (2005) Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood 106:2580-2589.
9. LaVaute T, et al. (2001) Targeted deletion of iron regulatory protein 2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet 27:209-214.
10. Smith SR, et al. (2004) Severity of neurodegeneration correlates with compromise of iron metabolism in mice with iron regulatory protein deficiencies. Ann NY Acad Sci 1012:65-83.
11. Galy B, et al. (2006) Iron homeostasis in the brain: Complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat Genet 38:967-969.
12. Ghosh MC, Ollivierre-Wilson H, Cooperman S, Rouault TA (2006) Reply to "Iron homeostasis in the brain: Complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse." Nat Genet 38:969-970.
13. Meyron-Holtz EG, Ghosh MC, Rouault TA (2004) Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306:2087-2090.
14. Smith SR, Ghosh MC, Ollivierre-Wilson H, Hang Tong W, Rouault TA (2006) Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development. Blood Cells Mol Dis 36:283-287.
15. Pantopoulos K, Hentze MW (1995) Rapid responses to oxidative stress mediated by iron regulatory protein. EMBO J 14:2917-2924.
16. Bouton C, Drapier JC (2003) Iron regulatory proteins as NO signal transducers. Sci STKE 2003:pe17.
17. Mitchell JB, et al. (2003) A low molecular weight antioxidant decreases weight and lowers tumor incidence. Free Radic Biol Med 34:93-102.
18. Schubert R, et al. (2004) Cancer chemoprevention by the antioxidant tempol in Atm-deficient mice. Hum Mol Genet 13:1793-1802.
19. Zhang QS, et al. (2008) Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice. Cancer Res 68:1601-1608.
20. Crawley JN (1999) Behavioral phenotyping of transgenic and knockout mice: Experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res 835:18-26.
21. Liou YC, et al. (2003) Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424:556-561.
22. Soule BP, et al. (2007) The chemistry and biology of nitroxide compounds. Free Radic Biol Med 42:1632-1650.
23. Hu G, Lyeth BG, Zhao X, Mitchell JB, Watson JC (2003) Neuroprotection by the stable nitroxide 3-carbamoyl-proxyl during reperfusion in a rat model of transient focal ischemia. J Neurosurg 98:393-396.
24. Tong WH, Rouault TA (2006) Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis. Cell Metab 3:199-210.
25. Trnka J, Blaikie FH, Smith RA, Murphy MP (2008) A mitochondria-targeted nitroxide is reduced to its hydroxylamine by ubiquinol in mitochondria. Free Radic Biol Med 44:1406-1419.
26. Bourdon E, et al. (2003) The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2. Blood Cells Mol Dis 31:247-255.
27. DePamphilis BV, Averill BA, Herskovitz T, Que LJ, Holm RH (1974) Synthetic analogs of the active sites of iron-sulfur proteins. VI. Spectral and redox characteristics of the tetranuclear clusters (Fe4S4(SR)4). 2-. J Am Chem Soc 96:4159-4167.
28. Drapier JC, Hirling H, Wietzerbin J, Kaldy P, Kuhn LC (1993) Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO J 12:3643-3649.
29. Soum E, Drapier JC (2003) Nitric oxide and peroxynitrite promote complete disruption of the [4Fe-4S] cluster of recombinant human iron regulatory protein 1. J Biol Inorg Chem 8:226-232.
30. Rouault TA, Cooperman S (2006) Brain iron metabolism. Semin Pediatr Neurol 13:142-148.
31. Metz JM, et al. (2004) A phase I study of topical Tempol for the prevention of alopecia induced by whole brain radiotherapy. Clin Cancer Res 10:6411-6417.
32. Coon KD, et al. (2006) Preliminary demonstration of an allelic association of the IREB2 gene with Alzheimer's disease. J Alzheimers Dis 9:225-233.
33. Hung RJ, et al. (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452:633-637.
34. Brew BJ (2007) Lost in translation: Again, another failed neuroprotection trial. Neurology 69:1308-1309.
35. Hyodo F, Matsumoto K, Matsumoto A, Mitchell JB, Krishna MC (2006) Probing the intracellular redox status of tumors with magnetic resonance imaging and redoxsensitive contrast agents. Cancer Res 66:9921-9928.
36. Zhang DL, Su D, Berczi A, Vargas A, Asard H (2006) An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes. Biochim Biophys Acta 1760:1903-1913.