Pediatric Neurology
Volume 25, Issue 2 , Pages 138-147 , August 2001

Iron overload, oxidative stress, and axonal dystrophy in brain disorders1

  • Chuang C Chiueh, PhD

      Affiliations

    • Unit on Neurodegeneration and Neuroprotection; Laboratory of Clinical Science, National Institute of Mental Health; National Institutes of Health; Bethesda, Maryland, USA
    • Corresponding Author InformationCommunications should be addressed to: Dr. Chiueh; NIMH; LCS; NIH 10/3D-41; Bethesda, MD 20892-1264

Received 9 November 2000 ,Accepted 20 February 2001.

References 

  1. Elejalde BR, de Elejalde MM, Lopez F. Hallervorden-Spatz disease. Clin Genet. 1979;16:1–18
  2. Taylor TD, Litt M, Kramer P, et al.  Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. [published erratum appears in Nat Genet 1997;16(1):109] Nat Genet. 1996;14:479–481
  3. Swaiman KF. Hallervorden-Spatz syndrome and brain iron metabolism. Arch Neurol. 1991;48:1285–1293
  4. Malandrini A, Fabrizi GM, Bartalucci P, et al.  Clinicopathological study of familial late infantile Hallervorden-Spatz disease (A particular form of neuroacanthocytosis). Childs Nerv Syst. 1996;12:155–160
  5. Arawaka S, Saito Y, Murayama S, Mori H. Lewy body in neurodegeneration with brain iron accumulation type 1 is immunoreactive for α-synuclein. Neurology. 1998;51:887–889
  6. Wakabayashi K, Fukushima T, Koide R, et al.  Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and Lewy body pathology. Acta Neuropathol (Berl). 2000;99:331–336
  7. Feliciani M, Curatolo P. Early clinical and imaging (high-field MRI) diagnosis of Hallervorden-Spatz disease. Neuroradiology. 1994;36:247–248
  8. Chiueh CC, Miyake H, Peng MT. Role of dopamine autoxidation, hydroxyl radical generation, and calcium overload in underlying mechanisms involved in MPTP-induced parkinsonism. Adv Neurol. 1993;60:251–258
  9. Gutteridge JM. Hydroxyl radicals, iron, oxidative stress, and neurodegeneration. Ann NY Acad Sci. 1994;738:201–213
  10. Sziraki I, Mohanakumar KP, Rauhala P, Kim HG, Yeh KJ, Chiueh CC. Manganese (A transition metal protects nigrostriatal neurons from oxidative stress in the iron-induced animal model of parkinsonism). Neuroscience. 1998;85:1101–1111
  11. Van Bergen P, Rauhala P, Spooner CM, Chiueh CC. Hemoglobin and iron-evoked oxidative stress in the brain (Protection by bile pigments, manganese and S-nitrosoglutathione). Free Radic Res. 1999;31:631–640
  12. Rauhala P, Khaldi A, Mohanakumar KP, Chiueh CC. Apparent role of hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside. Free Radic Biol Med. 1998;24:1065–1073
  13. Chiueh CC, Andoh T, Lai AR, Lai E, Krishna G. Neuroprotective strategies in Parkinson’s disease (Protection against progressive nigral injury induced by free radicals). Neurotoxicity Res. 2000;2:293–310
  14. Castelnau PA, Garrett RS, Palinski W, Witztum JL, Campbell IL, Powell HC. Abnormal iron deposition associated with lipid peroxidation in transgenic mice expressing interleukin-6 in the brain. J Neuropathol Exp Neurol. 1998;57:268–282
  15. Connor JR, Benkovic SA. Iron regulation in the brain (Histochemical, biochemical, and molecular considerations). Ann Neurol. 1992;32:S51–S61
  16. Moos T, Oates PS, Morgan EH. Iron-independent neuronal expression of transferrin receptor mRNA in the rat. Brain Res Mol Brain Res. 1999;72:231–234
  17. Boldt DH. New perspectives on iron (An introduction). Am J Med Sci. 1999;318:207–212
  18. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet. 1999;21:396–399
  19. Moos T, Trinder D, Morgan EH. Cellular distribution of ferric iron, ferritin, transferrin and divalent metal transporter 1 (DMT1) in substantia nigra and basal ganglia of normal and β2-microglobulin deficient mouse brain. Cell Mol Biol (Noisy-le-grand). 2000;46:549–561
  20. Harrison PM, Arosio P. The ferritins (Molecular properties, iron storage function and cellular regulation). Biochim Biophys Acta. 1996;1275:161–203
  21. Lin F, Girotti AW. Elevated ferritin production, iron containment, and oxidant resistance in hemin-treated leukemia cells. Arch Biochem Biophys. 1997;346:131–141
  22. Garner B, Roberg K, Brunk UT. Endogenous ferritin protects cells with iron-laden lysosomes against oxidative stress. Free Radic Res. 1998;29:103–114
  23. Oberle S, Polte T, Abate A, Podhaisky HP, Schroder H. Aspirin increases ferritin synthesis in endothelial cells (A novel antioxidant pathway). Circ Res. 1998;82:1016–1020
  24. Rouault TA, Haile DJ, Downey WE, et al.  An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein. Biometals. 1992;5:131–140
  25. Crichton RR, Ward RJ. Iron species in iron homeostasis and toxicity. Analyst. 1995;120:693–697
  26. Williams K, Wilson MA, Bressler J. Regulation and developmental expression of the divalent metal-ion transporter in the rat brain. Cell Mol Biol (Noisy-le-grand). 2000;46:563–571
  27. Sziraki I, Rauhala P, Koh KK, van Bergen P, Chiueh CC. Implications for atypical antioxidative properties of manganese in iron-induced brain lipid peroxidation and copper-dependent low density lipoprotein conjugation. Neurotoxicology. 1999;20:455–466
  28. Bondy SC, Guo SX. Lead potentiates iron-induced formation of reactive oxygen species. Toxicol Lett. 1996;87:109–112
  29. Mohanakumar KP, de Bartolomeis A, Wu RM, et al.  Ferrous-citrate complex and nigral degeneration (Evidence for free-radical formation and lipid peroxidation). Ann NY Acad Sci. 1994;738:392–399
  30. Rauhala P, Mohanakumar KP, Sziraki I, Lin AM, Chiueh CC. S-nitrosothiols and nitric oxide, but not sodium nitroprusside, protect nigrostriatal dopamine neurons against iron-induced oxidative stress in vivo. Synapse. 1996;23:58–60
  31. Mohanakumar KP, Hanbauer I, Chiueh CC. Neuroprotection by nitric oxide against hydroxyl radical-induced nigral neurotoxicity. J Chem Neuroanat. 1998;14:195–205
  32. Rauhala P, Chiueh CC. Effects of atypical antioxidative agents, S-nitrosoglutathione and manganese, on brain lipid peroxidation induced by iron leaking from tissue disruption. Ann NY Acad Sci. 2000;899:238–254
  33. Smith SL, Scherch HM, Hall ED. Protective effects of tirilazad mesylate and metabolite U-89678 against blood-brain barrier damage after subarachnoid hemorrhage and lipid peroxidative neuronal injury. J Neurosurg. 1996;84:229–233
  34. Torri C, Cafe C, Adinolfi D, et al.  Synaptosomal iron-dependent lipid peroxidation inhibition after subarachnoid hemorrhage by lazaroid in vivo treatment. Mol Chem Neuropathol. 1997;30:15–24
  35. Chiueh CC. Neuroprotective properties of nitric oxide. Ann NY Acad Sci. 1999;890:301–311
  36. Chiueh CC, Rauhala P. The redox pathway of S-nitrosoglutathione, glutathione and nitric oxide in cell to neuron communications. Free Radical Res. 1999;31:641–650
  37. Rauhala P, Lin AM, Chiueh CC. Neuroprotection by S-nitrosoglutathione of brain dopamine neurons from oxidative stress. FASEB J. 1998;12:165–173
  38. Andoh T, Lee SY, Chiueh CC. Preconditioning regulation of bcl-2 and p66shc by human NOS1 enhances tolerance to oxidative stress. FASEB J. 2000;14:2144–2146
  39. Chiueh CC, Andoh T. Nitric oxide (·NO) production through transfection and induction of NOS1 increases tolerance to 1-methyl-4-phenylpyrodinium (Mpp+)-induced neurotoxicity. (abstract) Soc Neurosci. 2000;26:10
  40. Lingor P, Unsicker K, Krieglstein K. GDNF and NT-4 protect midbrain dopaminergic neurons from toxic damage by iron and nitric oxide. Exp Neurol. 2000;163:55–62
  41. Schmidt J, Mertz K, Morgan JI. Regulation of heme oxygenase-1 expression by dopamine in cultured C6 glioma and primary astrocytes. Brain Res Mol Brain Res. 1999;73:50–59
  42. Xie CX, Mattson MP, Lovell MA, Yokel RA. Intraneuronal aluminum potentiates iron-induced oxidative stress in cultured rat hippocampal neurons. Brain Res. 1996;743:271–277
  43. Yang EY, Guo-Ross SX, Bondy SC. The stabilization of ferrous iron by a toxic β-amyloid fragment and by an aluminum salt. Brain Res. 1999;839:221–226
  44. Hawkins V, Shen Q, Chiueh CC. Kynostatin and 17β-estradiol prevent the apoptotic death of human neuroblastoma cells exposed to HIV-1 protease. J Biomed Sci. 1999;6:433–438
  45. Wang ZJ, Lam KW, Lam TT, Tso MO. Iron-induced apoptosis in the photoreceptor cells of rats. Invest Ophthalmol Vis Sci. 1998;39:631–633
  46. Sohn J, Yoon YH. Iron-induced cytotoxicity in cultured rat retinal neurons. Korean J Ophthalmol. 1998;12:77–84
  47. Yonekawa M, Okabe T, Asamoto Y, Ohta M. A case of hereditary ceruloplasmin deficiency with iron deposition in the brain associated with chorea, dementia, diabetes mellitus and retinal pigmentation (Administration of fresh-frozen human plasma). Eur Neurol. 1999;42:157–162
  48. Willmore LJ, Sypert GW, Munson JB. Recurrent seizures induced by cortical iron injection (A model of posttraumatic epilepsy). Ann Neurol. 1978;4:329–336
  49. Hammond EJ, Ramsay RE, Villarreal HJ, Wilder BJ. Effects of intracortical injection of blood and blood components on the electrocorticogram. Epilepsia. 1980;21:3–14
  50. Willmore LJ, Triggs WJ, Gray JD. The role of iron-induced hippocampal peroxidation in acute epileptogenesis. Brain Res. 1986;382:422–426
  51. Kabuto H, Yokoi I, Habu H, Willmore LJ, Mori A, Ogawa N. Reduction in nitric oxide synthase activity with development of an epileptogenic focus induced by ferric chloride in the rat brain. Epilepsy Res. 1996;25:65–68
  52. Csernansky JG, Csernansky CA, Bonnet KA, Hollister LE. Dopaminergic supersensitivity follows ferric chloride-induced limbic seizures. Biol Psychiatry. 1985;20:723–733
  53. Thomas CE, Ohlweiler DF, Taylor VL, Schmidt CJ. Radical trapping and inhibition of iron-dependent CNS damage by cyclic nitrone spin traps. J Neurochem. 1997;68:1173–1182
  54. Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation. Epilepsia. 1998;39:237–243
  55. Moos T, Morgan EH. Transferrin and transferrin receptor function in brain barrier systems. Cell Mol Neurobiol. 2000;20:77–95
  56. Chiueh CC, Murphy DL, Miyake H, Lang K, Tulsi PK, Huang SJ. Hydroxyl free radical (·OH) formation reflected by salicylate hydroxylation and neuromelanin. In vivo markers for oxidant injury of nigral neurons. Ann NY Acad Sci. 1993;679:370–375
  57. Rothwell NJ, Strijbos PJ. Cytokines in neurodegeneration and repair. Int J Dev Neurosci. 1995;13:179–185
  58. Sziraki I, Rauhala P, Chiueh CC. Novel protective effect of manganese against ferrous citrate-induced lipid peroxidation and nigrostriatal neurodegeneration in vivo. Brain Res. 1995;698:285–287
  59. Ying W, Han SK, Miller JW, Swanson RA. Acidosis potentiates oxidative neuronal death by multiple mechanisms. J Neurochem. 1999;73:1549–1556
  60. Porter JB, Huehns ER. The toxic effects of desferrioxamine. Baillieres Clin Haematol. 1989;2:459–474
  61. Marciani MG, Cianciulli P, Stefani N, et al.  Toxic effects of high-dose deferoxamine treatment in patients with iron overload (An electrophysiological study of cerebral and visual function). Haematologica. 1991;76:131–134
  62. Samuni A, Mitchell JB, DeGraff W, Krishna CM, Samuni U, Russo A. Nitroxide SOD-mimics. modes of action. Free Radic Res Commun. 1991;12/13:187–194
  63. Batinic-Haberle I, Liochev SI, Spasojevic I, Fridovich I. A potent superoxide dismutase mimic (Manganese β-octabromo-meso-tetrakis-(N-methylpyridinium-4-yl) porphyrin). Arch Biochem Biophys. 1997;343:225–233
  64. Brurok H, Ardenkjaer-Larsen JH, Hansson G, et al.  Manganese dipyridoxyl diphosphate (MRI contrast agent with antioxidative and cardioprotective properties?). Biochem Biophys Res Commun. 1999;254:768–772
  65. Salvemini D, Wang ZQ, Zweier JL, et al.  A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science. 1999;286:304–306
  66. Klivenyi P, St. Clair D, Wermer M, et al.  Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiol Dis. 1998;5:253–258
  67. Huang TT, Carlson EJ, Raineri I, Gillespie AM, Kozy H, Epstein CJ. The use of transgenic and mutant mice to study oxygen free radical metabolism. Ann NY Acad Sci. 1999;893:95–112
  68. Liu Y, Kato H, Nakata N, Kogure K. Temporal profile of heat shock protein 70 synthesis in ischemic tolerance induced by preconditioning ischemia in rat hippocampus. Neuroscience. 1993;56:921–927
  69. Emerson MR, Samson FE, Pazdernik TL. Effects of hypoxia preconditioning on expression of metallothionein-1,2 and heme oxygenase-1 before and after kainic acid-induced seizures. Cell Mol Biol (Noisy-le-grand). 2000;46:619–626
  70. Kaya H, Delibas N, Serteser M, Ulukaya E, Ozkaya O. The effect of melatonin on lipid peroxidation during radiotherapy in female rats. Strahlenther Onkol. 1999;175:285–288
  71. Lin AM, Ho L. Melatonin suppresses iron-induced neurodegeneration in rat brain. Free Radic Biol Med. 2000;28:904–911
  72. Kitani K, Kanai S, Ivy GO, Carrillo MC. Assessing the effects of deprenyl on longevity and antioxidant defenses in different animal models. Ann NY Acad Sci. 1998;854:291–306
  73. Tang YP, Ma YL, Chao CC, Chen KY, Lee EH. Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (−)-deprenyl and melatonin treatments. J Neurosci Res. 1998;53:593–604
  74. Wu RM, Murphy DL, Chiueh CC. Neuronal protective and rescue effects of deprenyl against Mpp+ dopaminergic toxicity. J Neural Transm Gen Sect. 1995;100:53–61
  75. Slooter AJ, Bronzova J, Witteman JC, Van Broeckhoven C, Hofman A, van Duijn CM. Estrogen use and early onset Alzheimer’s disease (A population-based study). J Neurol Neurosurg Psychiatry. 1999;67:779–781
  76. McCarty MF. Vascular nitric oxide, sex hormone replacement, and fish oil may help to prevent Alzheimer’s disease by suppressing synthesis of acute-phase cytokines. Med Hypotheses. 1999;53:369–374
  77. Marder K, Sano M. Estrogen to treat Alzheimer’s disease (Too little, too late? So what’s a woman to do?). Neurology. 2000;54:2035–2037
  78. Wilson ME, Dubal DB, Wise PM. Estradiol protects against injury-induced cell death in cortical explant cultures (A role for estrogen receptors). Brain Res. 2000;873:235–242
  79. Bolli R. The late phase of preconditioning. Circ Res. 2000;87:972–983
  80. Chiueh CC. Dopamine in the extrapyramidal motor function. A study based upon the MPTP-induced primate model of parkinsonism. Ann NY Acad Sci. 1988;515:226–238

PII: S0887-8994(01)00266-1

Pediatric Neurology
Volume 25, Issue 2 , Pages 138-147 , August 2001