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Oxygen Radical-Mediated Oxidation of Serotonin: Potential Relationship to Neurodegenerative Diseases

  • Monika Z. Wrona
  • Zhaoliang Yang
  • Jolanta Waskiewicz
  • Glenn Dryhurst
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

Oxygen free radicals have been implicated as a pathoetiological factor in aging1–5 and in a number of neurodegenerative brain disorders such as Alzheimer’s Disease,1,6–9 Parkinson’s Disease,10–12 transient cerebral ischemia13 and as a result of methamphetamine14–16 and ethanol17 abuse. The brain appears to be particularly vulnerable to oxygen radical-mediated damage, often referred to as oxidative stress, because of several biochemical features that include high oxygen consumption, high iron content of some brain regions,4 relatively low levels of protective enzymes and antioxidants such as the tocopherols,5 and high content of peroxidizable polyunsaturated fatty acids associated with lipid membranes. It seems to be rather widely accepted that oxygen radicals formed in the central nervous system (CNS) limit their damage to lipids, proteins and nucleic acids.5,7–13,18 However, it is of relevance to note that in all of the neurodegenerative brain disorders noted previously the serotonergic, noradrenergic and/or dopaminergic systems are seriously damaged. The neurotransmitters employed by these systems, 5-hydroxytryptamine (5-HT; serotonin), norepinephrine (NE), and dopamine (DA) are all very easily oxidized species.19–22 Thus, it seems likely that these neurotransmitters are also prime targets for oxygen radical-mediated oxidation. Accordingly, a major focus of research in this laboratory is to explore the hypothesis that the aberrant oxidative metabolites of these neurotransmitters might include endotoxins that contribute to the degenerative processes.23–26

Keywords

Ascorbic Acid GABAB Receptor Mediate Oxidation Incidental Lewy Body Disease System Degeneration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    M.A. Smith, L.M. Sayre, V.M. Monnier and G. Perry, Radical AGEing in Alzheimer’s Disease, Trends Neurosci., 18: 172–176 (1995).PubMedCrossRefGoogle Scholar
  2. 2.
    C.P. LeBel and S.C. Bondy, Oxidative damage and cerebral aging, Prog. Neurobiol, 38:601–609 (1992).PubMedCrossRefGoogle Scholar
  3. 3.
    C.W. Olanow, A radical hypothesis for neurodegeneration, Trends Neurosci., 16: 439–444 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    M. Gerlach, D. Ben-Shachar, P. Riederer and M.B.H. Yondim, Altered brain metabolism of iron as a cause of neurodegenerative disease? J. Neurochem., 63: 793–807 (1994).PubMedCrossRefGoogle Scholar
  5. 5.
    B. Halliwell and J.M.C. Gutteridge, Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts, Arch. Biochem. Biophys., 246: 501–514 (1986).PubMedCrossRefGoogle Scholar
  6. 6.
    R. A. Nixon and A.M. Cataldo, Free radicals, proteolysis and degeneration of neurons in Alzheimer’s Disease: how essential is the β-amyloid link? Neurobiol. Aging 15: 463–469 (1994).PubMedCrossRefGoogle Scholar
  7. 7.
    C.D. Smith, J.M. Carney, P.E. Starke-Reed, C.N. Oliver, E.R. Stadtman, R.A. Floyd and W.R. Markesbery, Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer’s Disease, Proc. Nat. Acad. Sci. U.S.A., 88: 10540–10543 (1991).CrossRefGoogle Scholar
  8. 8.
    K. Hensley, J.M. Carney, M.P. Mattson, M. Aksenova, M. Harris, J.F. Wu, R.A. Floyd and D.A. Butterfield, A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer’s Disease, Proc. Nat. Acad. Sci. U.S.A., 91: 3270–3274 (1994).CrossRefGoogle Scholar
  9. 9.
    K.V. Subbarao, J.S. Richardson and L.C. Ang, Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro, J. Neurochem., 55: 342–345 (1990).PubMedCrossRefGoogle Scholar
  10. 10.
    D.T. Dexter, C.J. Carter, F.R. Wells, F. Javoy-Agid, P. Jenner and C.D. Marsden, Basal lipid peroxidation in substantia nigra is increased in Parkinson’s Disease, J. Neurochem., 52: 381–389 (1987).CrossRefGoogle Scholar
  11. 11.
    P. Jenner, D.T. Dexter, J. Sian, A.H.V. Schapira and D.C. Marsden, Oxidative stress as a cause of nigral cell death in Parkinson’s Disease and incidental Lewy Body Disease, Ann. Neurol., (Suppl.), 32: S82–S87 (1992).PubMedCrossRefGoogle Scholar
  12. 12.
    P. Jenner, A.H.V. Schapira and CD. Marsden, New insights into the cause of Parkinson’s Disease, Neurology 42: 2241–2250 (1992).PubMedCrossRefGoogle Scholar
  13. 13.
    C.N. Oliver, P.E. Starke-Reed, E.R. Stadtman, G.J. Liu, J.M. Carney and R.A. Floyd, Oxidative damage to brain proteins, loss of glutamine synthetase activity and production of free radicals during ischemia/reperfusion-induced injury in gerbil brain, Proc. Nat. Acad. Sci. U.S.A., 87: 5144–5147 (1990).CrossRefGoogle Scholar
  14. 14.
    M.J. DeVito and G.C. Wagner, Methamphetamine-induced neuronal damage: a possible role for free radicals, Neuropharmacology 28: 1145–1150 (1989).CrossRefGoogle Scholar
  15. 15.
    L.S. Seiden and G. Vosmer, Formation of 6-hydroxydopamine in caudate nucleus of the rat after a single large dose of methylamphetamine, Pharmacol. Biochem. Behav., 21: 29–31 (1984).PubMedCrossRefGoogle Scholar
  16. 16.
    D.L. Commins, K.J. Axt, G. Vosmer and L.S. Seiden, 5,6-Dihydroxytryptamine, a serotonergic neurotoxin is formed endogenously in the rat brain, Brain Res., 403: 7–14 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    C. Montoliu, S. Vallés, J. Renau-Piqueras and C. Guerri, Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption, J. Neurochem., 63: 1855–1862 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    B. Halliwell, Reactive oxygen species and the central nervous system, J. Neurochem., 59: 1609–1623 (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    M.Z. Wrona and G. Dry hurst, Electrochemical oxidation of 5-hydroxytryptamine in aqueous solution at physiological pH, Bioorg. Chem., 18: 291–317 (1990).CrossRefGoogle Scholar
  20. 20.
    M.Z. Wrona and G. Dryhurst, Interactions of 5-hydroxytryptamine with oxidative enzymes, Biochem. Pharmacol, 41: 1145–1162 (1991).PubMedCrossRefGoogle Scholar
  21. 21.
    F. Zhang and G. Dryhurst, Oxidation chemistry of dopamine: possible insights into the age-dependent loss of dopaminergic nigrostriatal neurons, Bioorg. Chem., 21: 392–410 (1993).CrossRefGoogle Scholar
  22. 22.
    M.Z. Wrona, F. Zhang and G. Dryhurst, Electrochemical oxidations of central nervous system indoleamines, catecholamines and alkaloids. Potential significance into neurodegenerative diseases, J. Chin. Chem. Soc., 41: 231–249 (1994).Google Scholar
  23. 23.
    F. Zhang and G. Dryhurst, Effects of L-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson’s Disease, J. Med. Chem., 37: 1084–1098 (1994).PubMedCrossRefGoogle Scholar
  24. 24.
    M.Z. Wrona, Z. Yang, M. McAdams, S. O’Connor-Coates and G. Dryhurst, Hydroxyl radical-mediated oxidation of serotonin: potential insights into the neurotoxicity of methamphetamine, J. Neurochem., 64: 1390–1400 (1995).PubMedCrossRefGoogle Scholar
  25. 25.
    K-S. Wong, R.N. Goyal, M.Z. Wrona, C.L. Blank and G. Dryhurst, 7-S-Glutathionyl-tryptamine-4,5-dione: a possible aberrant metabolite of serotonin, Biochem. Pharmacol., 46: 1637–1652 (1993).PubMedCrossRefGoogle Scholar
  26. 26.
    M.Z. Wrona, R.N. Goyal, D. Turk, C.L. Blank and G. Dryhurst, 5,5′-Dihydroxy-4,4′-bitryptamine: a potentially aberrant neurotoxic metabolite of serotonin, J. Neurochem., 59: 1392–1398 (1992).PubMedCrossRefGoogle Scholar
  27. 27.
    P. Davies and A.F.J. Maloney, Selective loss of cerebral cholinergic neurons in Alzheimer’s Disease, Lancet 2: 1403 (1976).PubMedCrossRefGoogle Scholar
  28. 28.
    E.K. Perry, R.H. Perry, G. Blessed and B.E. Tomlinson, Necropsy evidence of cerebral cholinergic deficits in senile dementia, Lancet 1: 189 (1977).PubMedCrossRefGoogle Scholar
  29. 29.
    D.M. Bowen, S.J. Allen, J.S. Benton, M.J. Goodhart, E.A. Haan, A.M. Palmer, N.R. Sims, C.C.T. Smith, J.A. Spillane, M.M. Esiri, D. Neary, J.S. Snowden, G.K. Wilcock and A.N. Davison, Biochemical assessment of serotonergic and cholinergic dysfunction in cerebral atrophy in Alzheimer’s Disease, J. Neurochem., 41: 266–272 (1983).PubMedCrossRefGoogle Scholar
  30. 30.
    A.M. Palmer and D.M. Bowen, Neurochemical basis of dementia of the Alzheimer type: contribution of postmortem and antemortem studies, in: Biological Markers in Dementia of Alzheimer Type, C. Fowler, L.A. Carlson, C.G. Gottfries and B. Winblad, Eds., Smith-Gordon, London, 1990.Google Scholar
  31. 31.
    A.M. Palmer, P.T. Francis, D.M. Bowen, J.S. Benton, D. Neary, D.M.A. Mann and J.S. Snowden, Catecholaminergic neurones assessed ante-mortem in Alzheimer’s Disease, Brain Res., 414: 365–375 (1987).PubMedCrossRefGoogle Scholar
  32. 32.
    D.M.A. Mann, P.O. Yates and J. Hawkes, The noradrenergic system in Alzheimer and multi-infarct dementias, J. Neurol. Neurosurg. Psychiatry 45:113–119 (1982).PubMedCrossRefGoogle Scholar
  33. 33.
    B.E. Tomlinson, D. Irving and G. Blessed, Cell loss in locus ceruleus in senile dementia of the Alzheimer type, J. Neurol. Sci., 49: 418–421 (1981).CrossRefGoogle Scholar
  34. 34.
    T. Yamamoto and A. Hirano, Nucleus raphe dorsalis in Alzheimer’s Disease: neurofibrillary tangles and loss of large neurones, Ann. Neurol., 17: 573–577 (1985).PubMedCrossRefGoogle Scholar
  35. 35.
    A.M. Palmer, P.T. Francis, J.S. Benton, N.R. Sims, D.M.A. Mann, D. Neary, J.S. Snowden and D.M. Bowen, Presynaptic serotonergic dysfunction in patients with Alzheimer’s Disease, Brain Res., 48: 8–15 (1987).Google Scholar
  36. 36.
    D.M.A. Mann, P.O. Yates and B. Marcyniuk, Dopaminergic neurotransmitter systems in Alzheimer’s Disease and Down’s Syndrome in middle age, J. Neurol. Neurosurg. Psychiatry 50: 341–344 (1987).PubMedCrossRefGoogle Scholar
  37. 37.
    A.W. Proctor, A.M. Palmer, P.T. Francis, S.L. Lowe, D. Neary, D.M.A. Mann and D.M. Bowen, Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer’s Disease, J. Neurochem., 50: 790–802 (1988).CrossRefGoogle Scholar
  38. 38.
    B.T. Hyman, G.W. Van Hoesen and A. Damasio, Alzheimer’s Disease: Glutamate depletion in the hippocampal perforant pathway zone, Ann. Neurol., 22: 37–40 (1987).PubMedCrossRefGoogle Scholar
  39. 39.
    B.M. Hubbard and J.M. Anderson, Age-related variation in the neuron content of the cerebral cortex in senile dementia of the Alzheimer type, Neuropath. Appl. Neurobiol., 11: 309–382 (1985).CrossRefGoogle Scholar
  40. 40.
    M.J. Ball, Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with aging and dementia, Acta Neuropath., 37: 111–118 (1977).PubMedCrossRefGoogle Scholar
  41. 41.
    D.M.A. Mann, Neuropathological and neurochemical aspects of Alzheimer’s Disease, in: Psychopharmacology of the Aging Nervous System, L.L. Iversen, S.D. Iversen and S.H. Snyder, Eds.; Plenum Press, New York, 1988, pp. 1–67.Google Scholar
  42. 42.
    C.B. Saper, B.H. Wainer and D.C. German, Axonal and transneuronal transport in the transmission of neurobiological disease: potential role in system degenerations, including Alzheimer’s Disease, Neuroscience 23: 389–398 (1987).PubMedCrossRefGoogle Scholar
  43. 43.
    J. Hardy, R. Adolfsson, L. Alafuzoff, G. Bucht, J. Marcusson, P. Nyberg, E. Perdahl, P. Wester and B. Winblad, Transmitter defecits in Alzheimer’s Disease, Neurochem. Int., 7: 545–563 (1985).PubMedCrossRefGoogle Scholar
  44. 44.
    L. Volicer, P.J. Langlais, W.R. Matson, K.A. Mark and P.H. Gamache, Serotonergic system in dementia of the Alzheimer type. Abnormal forms of 5-hydroxytryptophan and serotonin in cerebrospinal fluid, Arch. Neurol., 42: 1158–1161 (1985).PubMedCrossRefGoogle Scholar
  45. 45.
    A. Slivka and G. Cohen, Hydroxyl radical attack on dopamine, J. Biol. Chem., 260: 15466–15472 (1985).PubMedGoogle Scholar
  46. 46.
    M.J. Del Rio, C.V. Pardo, J. Pinxteren, W. DePotter, G. Ebinger and G. Vauquelin, Binding of serotonin and dopamine to serotonin binding proteins’ in bovine frontal cortex: evidence for iron-induced oxidative mechanisms, Eur. J. Pharmacol., 247: 11–23 (1993).CrossRefGoogle Scholar
  47. 47.
    S. Udenfriend, C.T. Clark, J. Axelrod and B.B. Brodie, Ascorbic acid in aromatic hydroxylation, J. Biol. Chem., 208: 731–738 (1954).PubMedGoogle Scholar
  48. 48.
    S. Singh, J-F. Jen and G. Dryhurst, Autoxidation of the indolic neurotoxin 5,6-dihydroxytryptamine, J. Org, Chem., 55: 1484–1489 (1990).CrossRefGoogle Scholar
  49. 49.
    S. Singh and G. Dryhurst, Further insights into the oxidation chemistry and biochemistry of the serotonergic neurotoxin 5,6-dihydroxytryptamine, J. Med. Chem., 33: 3035–3044 (1990).PubMedCrossRefGoogle Scholar
  50. 50.
    K-S. Wong and G. Dryhurst, Tryptamine-4,5-dione: properties and reactions with glutathione, Bioorg. Chem., 18: 253–264 (1990).CrossRefGoogle Scholar
  51. 51.
    H.G. Baumgarten, H.P. Klemm, L. Lachenmeyer, A Björklund, W. Lovenberg and H.G. Schlossberger, Mode and mechanism of action of neurotoxic indoleamines: a review and progress report, Ann. New York Acad. Sci., 305: 3–24 (1976).CrossRefGoogle Scholar
  52. 52.
    S. Singh, M.Z. Wrona and G. Dryhurst, Synthesis and reactivity of the putative neurotoxin tryptamine-4,5-dione, Bioorg. Chem., 35: 82–93 (1992).Google Scholar
  53. 53.
    Z. Fa, R.N. Goyal, C.L. Blank and G. Dryhurst, Oxidation chemistry of the central mammalian alkaloid l-methyl-6-hydroxy-l,2,3,4-tetrahdyro-β-carboline, J. Med. Chem., 35: 82–93 (1992).CrossRefGoogle Scholar
  54. 54.
    N. Bowery, GAB AB receptors and their significance in mammalian pharmacology, Trends Pharmacol. Sci., 10: 401–407 (1989).PubMedCrossRefGoogle Scholar
  55. 55.
    R. Spector and J. Eells, Deoxynucleoside and vitamin transport into the central nervous system, Fed. Proc., 43: 196–200 (1984).PubMedGoogle Scholar
  56. 56.
    A. Slivka, C. Mytilineou and G. Cohen, Histochemical evaluation of glutathione in brain, Brain Res., 409: 275–284 (1987).PubMedCrossRefGoogle Scholar
  57. 57.
    D.W. Choi, Ionic dependence of glutamate neurotoxicity, J. Neurosci., 7: 369–379 (1987).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Monika Z. Wrona
    • 1
  • Zhaoliang Yang
    • 1
  • Jolanta Waskiewicz
    • 1
  • Glenn Dryhurst
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of OklahomaNormanUSA

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