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Dopamine thioethers: Formation in brain and neurotoxicity

Neurotoxicity Research volume 4, pages 663–669 (2002)Cite this article

Abstract

Dopamine (DA) oxidation is proposed to be a significant contributor to some forms of neurodegeneration, although the mechanisms are not fully resolved. Recent results from in vitro and in vivo models have suggested that some products of oxidized DA metabolized along the mercapturic acid pathway (MAP) may contribute to dopaminergic neurodegeneration. Here we review recent findings on the localization of MAP enzymes in human brain, as well as the concentration and neurotoxicity of their DA thioether products.

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Abbreviations

6-OHDA:

6-hydroxydopamine

AcNBCys:

N-acetyl-S-(4-nitrobenzyl)-l-cysteine

AD:

Alzheimer’s disease

CNAT:

cysteine S-conjugate N-acetyltransferase

CysDA:

5-S-cysteinyldopamine

DA:

dopamine

DLB:

Dementia with Lewy Bodies

DOPAC:

3,4-dihydroxyphenylacetic acid

DP:

dipeptidase

γ-GT:

γ-glutamyltranspeptidase

GSH:

glutathione

GSH-DA:

5-S-glutathionyldopamine

GST:

glutathione-S-transferase

HVA:

homovanilic acid

MAP:

mercapturic acid pathway

MerDA:

mercapturyldopamine

NBCys:

S-(4-nitrobenzyl)-l-cysteine

PD:

Parkinson’s disease

PMI:

post-mortem interval

TH:

tyrosine hydroxylase

References

  • Berman, S., Zigmond, M. and Hastings, T. (1996) “Modification of dopamine transporter function: effect of reactive oxygen species and dopamine”, J. Neurochem. 67, 593–600.

    PubMed  CAS  Google Scholar 

  • Campbell, J., Corrigall, A. and Kirsch, R. (1991) “Immunohistologic localization of alpha, mu, and pi class glutathione S-transferases in human tissue”, Cancer 67, 1608–1613.

    PubMed  Article  CAS  Google Scholar 

  • Carder, P., Hume, R., Fryer, A., Strange, R., Lauder, J. and Bell, J. (1990) “Glutathione S-transferase in human brain”, Neuropathol. Appl. Neurobiol. 16, 293–303.

    PubMed  Article  CAS  Google Scholar 

  • Clemens, J. and Phebus, L. (1988), “Dopamine depletion protects striatal neurons from ischemia-induced cell death”, Life Sci. 42, 707–713.

    PubMed  Article  CAS  Google Scholar 

  • Conway, K.A., Rochet, J.C., Bieganski, R.M. and Lansbury, P.T. (2001) “Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct”, Science 294, 1257–1258.

    Article  Google Scholar 

  • Dagnino-Subiabre, A., Cassels, B.K., Baez, S., Johansson, A.S., Mannervik, B. and Segura-Aguilar, J. (2000) “Glutathione transferase M2-2 catalyzes conjugation of dopamine and DOPA o-quinones”, Biochem. Biophys. Res. Commun. 274, 32–36.

    PubMed  Article  CAS  Google Scholar 

  • Davidson, C., Gow, A.J., Lee, T.H. and Ellinwood, E.H. (2001) “Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment”, Brain Res. Rev. 36, 1–22.

    PubMed  Article  CAS  Google Scholar 

  • Duffel, M. and Jakoby, W. (1982) “Cysteine-S-conjugate N-acetyltransferase from rat kidney microsomes”, Mol. Pharmacol. 21, 444–448.

    PubMed  CAS  Google Scholar 

  • Fleckenstein, A., Gibb, J. and Hanson, G. (2000) “Differential effects of stimulants on monoaminergic transporters: pharmacological consequences and implications for neurotoxicity”, Eur. J. Pharmacol. 406, 1–13.

    PubMed  Article  CAS  Google Scholar 

  • Fornstedt, B., Rosengren, E. and Carlsson, A. (1986) “Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa, and dopac in the brains of eight mammalian species”, Neuropharmacology 25, 451–454.

    PubMed  Article  CAS  Google Scholar 

  • Fornstedt, B., Rosengren, E. and Carlsson, A. (1989) “The apparent autoxidation rate of catechols in dopamine-rich regions of human brains increases with degree of depigmentation of substantia nigra”, J. Neural. Transm. 1, 279–295.

    Article  CAS  Google Scholar 

  • Fornstedt, B., Pileblad, E. and Carlsson, A. (1990) “In vivo autoxidation of dopamine in guinea pig striatum increases with age”, J. Neurochem. 55, 655–659.

    PubMed  Article  CAS  Google Scholar 

  • Graham, D.G. (1978) “Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones”, Mol. Pharmacol. 14, 633–643.

    PubMed  CAS  Google Scholar 

  • Graham, D.G., Tiffany, S.M., Bell, Jr. W.R. and Gutknecht, G.F. (1978) “Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro”, Mol. Pharmacol. 14, 644–653.

    PubMed  CAS  Google Scholar 

  • Graham, D., Picklo, M., Zhang, J., Amarnath, V. and Montine, T. (2000) “Role of quinones in catechol neurotoxicity”, In: Creveling, C.R. ed, Role of Catechol Quinone Species in Cellular Toxicity (E.P. Graham Publishing Co., Mountain Home, TN), pp. 11–30.

    Google Scholar 

  • Hanigan, M. and Frierson, H. (1996) “Immunohistochemical detection of γ-glutamyl transpeptidase in normal human tissue”, J. Histochem. Cytochem. 44, 1101–1108.

    PubMed  CAS  Google Scholar 

  • Johnson, J., Barbary, A., Kornguth, S., Brugge, J. and Siegel, F. (1993) “Glutathione S-tranferase isoenzymes in rat brain neurons and glia”, J. Neurosci. 13, 2013–2023.

    PubMed  CAS  Google Scholar 

  • Li, H., Shen, X.M. and Dryhurst, G. (1998) “Brain mitochondria catalyze the oxidation of 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1) to intermediates that irreversibly inhibit complex I and scavenge glutathione: potential relevance to the pathogenesis of Parkinson’s disease”, J. Neurochem. 71, 2049–2062.

    PubMed  CAS  Article  Google Scholar 

  • Louis, E., Klatka, L.A., Liu, Y. and Fahn, S. (1997) “Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson’s disease”, Neurology 48, 376–380.

    PubMed  CAS  Google Scholar 

  • McKeith, I.G., Perry, E.K. and Perry, R.H. (1999) “Report of the second dementia with Lewy body international workshop: diagnosis and treatment. Consortium on dementia with Lewy bodies”, Neurology 53, 902–905.

    PubMed  CAS  Google Scholar 

  • Miller, D.M., Buettner, G.R. and Aust, S.D. (1990) “Transition metals as catalysts of ‘autoxidation’ reactions”, Free Radic. Biol. Med. 8, 95–108.

    PubMed  Article  CAS  Google Scholar 

  • Miller, R.T., Lau, S.S. and Monks, T.J. (1995) “Metabolism of 5-(glutathion-S-yl)-α-methyldopamine following intracerebroventricular administration to male Sprague-Dawley rats”, Chem. Res. Toxicol. 8, 634–641.

    PubMed  Article  CAS  Google Scholar 

  • Monks, T.J. and Lau, S.S. (1992) “Toxicology of quinonethioethers”, Crit. Rev. Toxicol. 22, 243–270.

    PubMed  Article  CAS  Google Scholar 

  • Montine, T.J., Farris, D.B. and Graham, D.G. (1995) “Covalent crosslinking of neurofilament proteins by oxidized catechols as a potential mechanism of Lewy body formation”, J. Neuropathol. Exp. Neurol. 54, 311–319

    PubMed  Article  CAS  Google Scholar 

  • Parkinson, A. (2001) “Biotransformation of Xenobiotics” In: Klaassen, C., ed, Casarett & Doull’s Toxicology (McGraw-Hill, New York, NY), pp. 133–224.

    Google Scholar 

  • Picklo, M.J., Amaranth, V., Graham, D.G. and Montine, T.J. (1999) “Endogenous catechol thioethers may be pro-oxidant or antioxidant”, Free Radio. Biol. Med. 27, 271–277.

    Article  CAS  Google Scholar 

  • Rosengren, E., Linder-Eliasson, E. and Carlsson, A. (1985) “Detection of 5-S-cysteinyldopamine in human brain”, J. Neural. Transm. 63, 247–253.

    PubMed  Article  CAS  Google Scholar 

  • Sandoval, V., Riddle, E., Ugarte, Y., Hanson, G. and Fleckenstein, A. (2001) “Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model”, J. Neurosci. 21, 1413–1419.

    PubMed  CAS  Google Scholar 

  • Segura-Aguilar, J. and Lind, C. (1989) “On the mechanisms of the Mn3+-induced neurotoxicity of dopamine: prevention of quinone-derived oxygen toxicity by DT diaphorase and superoxide dismutase”, Chem. Biol. Interact. 72, 309–324

    PubMed  Article  CAS  Google Scholar 

  • Shen, X.M., Xia, B., Wrona, M.Z. and Dryhurst, G. (1996) “Synthesis, redox properties, in vivo formation, and neurobehavioral effects of N-acetylcysteinyl conjugates of dopamine: possible metabolites of relevance to Parkinson’s disease”, Chem. Res. Toxicol. 9, 1117–1126.

    PubMed  Article  CAS  Google Scholar 

  • Sian, J., Dexter, D.T. and Lees, A.J. (1994) “Glutathione related enzymes in brain in Parkinson’s disease”, Ann. Neurol. 36, 356–361.

    PubMed  Article  CAS  Google Scholar 

  • Sidell, K., Olson, S., Ou, J., Zhang, Y., Amarnath, V. and Montine, T. (2001) “Cysteine and mercapturate conjugates of oxidized dopamine are in human striatum but only the cysteine conjugate impedes dopamine trafficking in vitro and in vivo”, J. Neurochem 79, 510–521.

    PubMed  Article  CAS  Google Scholar 

  • Smythies, J. (2000) “The adrenochrome hypothesis of schizophrenia revisited”, Neurotox. Res. 4, 147–150.

    Article  Google Scholar 

  • Spencer, J.P.E., Jenner, P., Daniel, S.E., Lees, A.J., Marsden, D.C. and Halliwell, B. (1998) “Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease: possible mechanisms of formation involving reactive oxygen species”, J. Neurochem. 71, 2112–2122.

    PubMed  CAS  Google Scholar 

  • Spencer, J.P.E., Whitman, M., Jenner, P. and Halliwell, B. (2002) “5-S-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons”, J. Neurochem. 81, 122–129.

    PubMed  Article  CAS  Google Scholar 

  • Yamaguchi, T., Takei, N., Araki, K., Ishii, K., Nagano, T., Ichikawa, T. and Nawa, H. (2000) “Molecular characterization of a novel gamma-glutamyltranspeptidase homologue found in rat brain”, J. Biochem. 128, 101–106.

    PubMed  CAS  Google Scholar 

  • Zhang, J., Kravtsov, V., Amarnath, V., Picklo, M., Graham, D. and Montine, T. (2000) “Enhancement of dopaminergic neurotoxicty by the mercapturate of dopamine: relevance to Parkinson’s Disease”, J. Neurochem. 74, 970–978.

    PubMed  Article  CAS  Google Scholar 

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Affiliations

  1. Department of Pathology, University of Washington, Harborview Medical Center, Box 359791, 98104, Seattle, WA, USA

    Kathleen S. Montine, Kathrin R. Sidell, Jing Zhang & Thomas J. Montine

Authors
  1. Kathleen S. Montine
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  2. Kathrin R. Sidell
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  3. Jing Zhang
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  4. Thomas J. Montine
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Correspondence to Kathleen S. Montine.

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Montine, K.S., Sidell, K.R., Zhang, J. et al. Dopamine thioethers: Formation in brain and neurotoxicity. neurotox res 4, 663–669 (2002). https://doi.org/10.1080/1029842021000045435

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  • DOI: https://doi.org/10.1080/1029842021000045435

Keywords

  • Dopamine
  • Catecholamine
  • Glutathione
  • Mercapturic acid pathway