Skip to main content

Neurotoxicity due to o-Quinones: Neuromelanin formation and possible mechanisms for o-Quinone detoxification

Neurotoxicity Research volume 1, pages 153–169 (1999)Cite this article

Abstract

o-Quinones are easily formed by oxidation of physiologically relevant catechols. These reactions mainly occur in two specialized cells, catecholaminergic neurons and melanocytes. Both types of cells are related ontogenetically, as they arise from the neural crest during the developmental differentiation. o-Quinones are used to form melanin, a protective pigment formed by different mechanisms in melanocytes and catecholaminergic neurons. However, the reactivity of these quinones makes their presence in the cytosol dangerous for the cell survival and these compounds have been proposed as degenerative and apoptotic agents. Thus, melanin-producing cells show several potential mechanisms to protect themselves against the noxious effects of o-quinones. In melanocytes, the most effective autoprotecting mechanisms are the existence of melanosomes as a confined site for melano-synthesis and the action of tyrosinase related protein 2 (TRP2) to derive L-dopachrome to 5,6-dihydroxy-indole-2-carboxylic acid minimizing the formation of 5,6-dihydroxyindole. In catecholaminergic neurons, recent data suggest that glutathione transferase (GST M2-2 isoenzyme) and macrophage migration inhibitory factor (MIF) are very effective in preventing long-lived formation of dopaminechrome and nora-drenochrome, although the detoxification reactions are different (conjugation to GSH or isomerization respectively). These mechanisms are less efficient for adrenochrome, although MIF and GST M1-1 could also catalyze similar reactions using this compound as substrate. In addition, the formation of adrenochrome is still under discussion, and adrenolutin formation could contribute to deactivate its harmful effects. The contribution of D-dopachrome tautomerase to these mechanisms is yet unknown, although in contrast to MIF, that enzyme does not recognize cate-cholaminechromes as substrates. Diaphorase could also be protective against quinones, since this enzyme catalyzes their bielectronic reduction back to catechols, thus preventing the formation of chrome species. This activity has been described in melanocytes and neurons, so that its contribution should be further investigated. In contrast to diaphorase, cytochrome P450 reductase should not be considered a protective enzyme, since its monoelectronic reduction of quinones leads to formation of semiquinones, that is even more noxious than the quinones.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Reference

  • Aroca, P., Solano, R, Garcia-Borron, J.C. and Lozano, J. A. (1990) Regulation of mammalian melanogenesis I. Partial purification and characterization of a dopachrome converting factor: dopachrome tautomerase.Biochim. Biophys. Acta,1035, 266–275.

    PubMed  CAS  Google Scholar 

  • Aroca, P., Solano, E, Garcia-Borron, J.C. and Lozano, J.A. (1991) Specificity of dopachrome tautomerase and inhibition by carboxylated indoles.Biochem. J.,277, 393–397.

    PubMed  CAS  Google Scholar 

  • Aroca, P., Solano, R, Salinas, C, Garcia-Borron, J.C. and Lozano, J.A. (1992) Regulation of the final phase of mammalian melanogenesis. The role of dopachrome tautomerase and the ratio between 5,6-dihydroxyindole-2-carboxylic acid and 5,6-dihydroxyindole.Eur.J. Biochem.,208, 155–163.

    PubMed  Article  CAS  Google Scholar 

  • Baez, S., Linderson, Y. and Segura-Aguilar, J. (1994) Superoxide dismutase and catalase prevent the formation of reactive oxygen species during reduction of cyclized dopa ortho-quinone by DT-diaphorase.Chem. Biol. Interact.,93, 103–116.

    PubMed  Article  CAS  Google Scholar 

  • Baez, S., Linderson, Y. and Segura-Aguilar, J. (1995) Superoxide dismutase and catalase enhance autooxidation during oneelectron reduction of aminochrome by NADPH-cytochrome P-450 reductase.Biochem. Mol. Med.,54, 12–18.

    PubMed  Article  CAS  Google Scholar 

  • Baez, S., Segura-Aguilar, J., Widersten, M., Johansson, A.S. and Mannervik, B. (1997) Glutathione transferases catalyse the detoxification of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes.Biochem. J.,324, 25–28.

    PubMed  CAS  Google Scholar 

  • Battyani, Z., Xerri, L., Hassoun, J., Bonerandi, J. and Grob, J. (1993) Tyrosinase gene expression in human tissues.Pigment Cell Res.,6, 400–405.

    PubMed  Article  CAS  Google Scholar 

  • Beal, M.R, Kowall, N.W., Ellison, D.W., Mazurek, M.R, Swartz, K.J. and Martin, J.B. (1986) Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid.Nature,321, 168–171.

    PubMed  Article  CAS  Google Scholar 

  • Ben-Shachar, D., Zuk, R. and Glinka, Y. (1995) Dopamine neurotoxicity: inhibition of mitochondrial respiration.J. Neurochem.,64, 718–723.

    PubMed  CAS  Google Scholar 

  • Bentley, R. and Campbell, I.M. (1974) Biological reactions of quinones. In:The Chemistry of the Quininoid Compounds. Part I, Patai (Ed.) John Wiley & Sons, London, pp. 683–736.

    Google Scholar 

  • Berlett, B.S. and Stadtman, E.R. (1997) Protein oxidation in aging, disease, and oxidative stress.J. Biol. Chem.,272, 20313–20316.

    PubMed  Article  CAS  Google Scholar 

  • Blocki, R, Schlievert, P. and Wackett, L. (1992) Rat liver protein linking chemical and immunological detoxification systems.Nature,360, 269–270.

    PubMed  Article  CAS  Google Scholar 

  • Bloom, B.R. and Bennett, B. (1966) Mechanism of a reactionin vitro associated with delay-type Hypersensitivity.Science,153, 80–82.

    PubMed  Article  CAS  Google Scholar 

  • Breathnach, A. (1988) Extra-cutaneous melanin.Pigment Cell Res.,1, 234–237.

    PubMed  Article  CAS  Google Scholar 

  • Carstam, R., Brinck, C, Hindemith-Augustsson, A., Rorsman, H. and Rosengren, E. (1991) The neuromelanin of the human substantia nigra.Biochim. Biophys. Acta,1097, 152–160.

    PubMed  CAS  Google Scholar 

  • Chedekel, M.R., Land, E.J., Thompson, A. and Truscott, T.G. (1984) Early steps in the free radical polymerisation of 3,4-dihydroxyphenylalanine (Dopa) into melanin.J. Chem. Soc. Chem. Commun., 1170–1172.

  • Comstock, K.E., Widersten, M., Hao, X.Y., Henner, D.W. and Mannervik, B. (1994) A comparison of the enzymatic and physicochemical properties of human glutathione transferase M4-4 and three other human Mu class enzymes.Arch. Biochem. Biophys.,311, 487–495.

    PubMed  Article  CAS  Google Scholar 

  • Cooksey, C.J., Garratt, P.J., Land, E.J, Pavel, S., Ramsden, C.A., Riley, PA. and Smit, N.P.M. (1997) Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase.J. Biol. Chem.,272, 26226–26235.

    PubMed  Article  CAS  Google Scholar 

  • D’Amato, R.J., Lipman, Z.P. and Snyder, S.H. (1986) Selectivity of the Parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin.Science,231, 987–989.

    PubMed  Article  CAS  Google Scholar 

  • Dietrich, R. and Erwin, V. (1980) Biogenic amine aldehydes condensation products: tetrahydropapaverolines and tryptolines.Ann. Rev. Pharm. Toxicol.,20, 55–80.

    Article  Google Scholar 

  • D’Ischia, M. and Prota, G. (1997) Biosynthesis, structure and function of neuromelanin and its relation to Parkinson’s disease.Pigment Cell Res.,10, 370–376.

    PubMed  Article  CAS  Google Scholar 

  • Fornstedt, B., Brun, A., Ropsengren, E. and Carlsson, A. (1989) The apparent autooxidation rate of catechols in dopamine-rich regions of human brains increases with the degree of depigmentation of substantia nigra.J. Neural. Transm.1(P-D section) 279–295.

    Article  CAS  Google Scholar 

  • Goldgeier, M., Klein, L., Klein-Angerer, S., Moellmann, G. and Nordlund, J. (1984) The distribution of melanocytes in the leptomeninges of the human brain.J. Invest. Dermatol,82, 235–238.

    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 

  • Haavik, J., Almas, B. and Flatmark, T. (1997) Generation of reactive oxygen species by tyrosine hydroxylase, a possible contribution to the degeneration of dopaminergic neurons?J. Neurochem.,68, 328–332.

    CAS  Google Scholar 

  • Haavik, J. (1997) L-DOPA is a substrate for tyrosine hydroxylase.J. Neurochem.,69, 1720–1728.

    PubMed  CAS  Article  Google Scholar 

  • Haglund, L., Kohler, C., Haaparanta, T., Goldstein, M. and Gustafsson, J.A. (1984) Presence of NADPH-cytochrome P-450 reductase in central catecholaminergic neurons.Nature,307, 259–262.

    PubMed  Article  CAS  Google Scholar 

  • Hastings, T.G. (1995) Enzymatic oxidation of dopamine: The role of prostaglandin H synthase.J. Neurochem.,64, 919–924.

    PubMed  CAS  Google Scholar 

  • Hirsch, E., Graybiel, A.N. and Agid, Y.A. (1988) Melanized dopaminergic neurons are differentially suceptible to degeneration in Parkinson’s disease.Nature,334, 345–348.

    PubMed  Article  CAS  Google Scholar 

  • Hirsch, E.C., Brandel, J.P., Galle, P., Javoy-Agid, F. and Agid, Y. (1991) Iron and aluminium increase in the substantia nigra of patients with Parkinson’s disease: a X-ray microanalysis.J. Neurochem,56, 446–451.

    PubMed  Article  CAS  Google Scholar 

  • Hope, B.T., Michael, G.J., Knigge, K.M. and Vicent, S.R. (1991) Neuronal NADPH diaphorase is a nitric oxide synthase.Proc. Natl. Acad. Sci. USA,88, 2811–2814.

    PubMed  Article  CAS  Google Scholar 

  • Inoue, S., Hasegawa, K., Ito, S., Ozeki, H., Solano, R, Jimenez-Cervantes, C, Wakamatsu, K. and Fujita, K. (1995) Antimelanoma effect of 4-S-cysteaminyIcatechol, an activated form of 4-S-cysteaminylphenol.Cancer Res.,55, 2603–2607.

    PubMed  CAS  Google Scholar 

  • Jaiswal, A.K. (1994) NAD(P)H: quinone oxidoreductasel (DT diaphorase) specifically prevents the formation of benzo[a]-pyrene quinone-DNA adducts generated by cytochrome P4501A1 and P450 reductase.Proc. Natl. Acad. Sci. USA,91, 8413–8417.

    PubMed  Article  Google Scholar 

  • Jenner, P., Dexter, D.T., Sian, J., Schapira, A.H.V. and Marsden, CD. (1992) Oxidative stress as a cause of neuronal death in Parkinson’s disease and incidental Lewy body disease.Ann. Neuro.32, S82-S87.

    Article  CAS  Google Scholar 

  • Jimenez-Cervantes, C, Solano, E, Kobayashi, T., Urabe, K., Hearing, V.J., Lozano, J.A. and Garcia-Borron, J.C. (1994) A new enzymatic function in the melanogenic pathway: The DHICA oxidase activity of tyrosinase related protein 1 (TRP-1).J. Biol. Chem.,269, 17993–18001.

    PubMed  CAS  Google Scholar 

  • Kastner, A., Hirsch, C, Lejeune, O., Javoy-Agid, R, Rascol, O. and Agid, Y. (1992) Is the vulnerability of neurons in the substantia nigra of patients with Parkinson’s disease related to their neuromelanin content?J. Neurochem.,59, 1080–1089.

    Article  CAS  Google Scholar 

  • King, T.E. (1982) Ubiquinone proteins in cardiac mitochondria. In ‘Function of Quinones in Energy Conserving Systems’ (edited by B.L. Trumpower). Academic press, New York, pp. 3–25.

    Google Scholar 

  • Kobayashi, T., Urabe, K., Winder, A., Jimenez-Cervantes, C, Imokawa, G., Brewington, T., Solano, E, Garcia-Borron, J.C. and Hearing, V.J. (1994) Tyrosinase Related Protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis.EMBOJ.13, 5818–5825.

    CAS  Google Scholar 

  • Korytowski, W.L., Sarna, T. and Zareba, M. (1995) Antioxidant action of neuromelanin. The mechanism of inhibitory effect on lipid peroxidation.Arch. Biochem. Biophys.319, 142–148.

    CAS  Google Scholar 

  • Le Douarin, N.M. (1982)The Neural Crest. Cambridge. Cambridge University Press.

    Google Scholar 

  • Lerner, A. and Fitzpatrick, T.B. (1950) Biochemistry of melanin formation.Physiol. Rev.,30, 91–126.

    PubMed  CAS  Google Scholar 

  • Lind, C, Hochstem, P. and Ernster, L. (1982) DT-diaphorase as a quinone reductase: a cellular control device against semiquinone and superoxide formation.Arch. Biochem. Biophys.,216, 33–40.

    Article  Google Scholar 

  • Linderson, Y, Baez, S. and Segura-Aguilar, J. (1994) The protective effect of superoxide dismutase and catalase against formation of reactive oxygen species during reduction of cyclized norepinephrine ortho-quinone by DT-diaphorase.Biochim. Biophys. Acta,1200, 197–204.

    PubMed  CAS  Google Scholar 

  • Mann, D.M.A. and Yates, P.O. (1983) Possible role of neuromelanin in the pathogenesis of Parkinson’s disease.Mech. Aging Dev.,21, 193–203.

    PubMed  Article  CAS  Google Scholar 

  • Mannervik, B., Awasthi, Y.C., Board, P.G., Hayes, J.D., Di Ilio, C, Ketterer, B., Listowsky, I., Morgenstern, R., Muramatsu, M., Pearson, W.R., Pickett, C.B., Sato, K., Widersten, M. and Wolf, C.R. (1992) Nomenclature for human glutathione transferases.Biochem. J.,282, 305–308.

    PubMed  CAS  Google Scholar 

  • Matsunaga, J., Sinha, D., Pannell, L., Santis, C, Solano, E, Wistow, G. and Hearing, V.J. (1999) Enzyme activity of macrophage migration inhibitory factor (MIF) towards oxidized catecholamines.J. Biol. Chem.,274, 3268–3271.

    PubMed  Article  CAS  Google Scholar 

  • Mattammal, M.B., Strong, R., Lakshmi, V.M., Chung, H.D. and Stephenson, A.H. (1995) Prostaglandin H synthetasemediated metabolism of dopamine: implication for Parkinson’s disease.J. Neurochem.,64, 1645–1654.

    PubMed  CAS  Google Scholar 

  • Mikayama, T, Nakano, T, Gomi, H., Nakagawa, Y, Liu, Y, Sato, M., Iwamatsu, A., Ishii, Y, Weiser, W.Y and Ishizaka, K. (1993) Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor.Proc. Natl. Acad. Sci. USA,90, 10056–10060.

    PubMed  Article  CAS  Google Scholar 

  • Miranda, M., Botti, D., Bonfigli, A., Ventura, T. and Arcadi, A. (1984) Tyrosinase-like activity in normal human substantia nigra.Gen. Pharmacol,15, 541–544.

    PubMed  CAS  Google Scholar 

  • Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A. (1987) Restriction patterns of model DNA treated with 5,6-dihydroxyindole, a potent cytotoxic intermediate of melanin synthesis: effect of UV irradiation.Mutagenesis,2, 45–50.

    PubMed  Article  CAS  Google Scholar 

  • Nagatsu, T. and Yoshida, M. (1988) An endogenous substance of brain, tetrahydroisoquinoline, produces Parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the negrostriatal regions.Neuroscience Lett.,87, 178–182.

    Article  CAS  Google Scholar 

  • Niwa, T, Takeda, N., Kaneda, N., Hashizume, Y and Nagatsu, T. (1987) Presence of tetrahydroisoquinoline in Parkinson and in normal human brain.Biochem. Biophys. Res. Commun.,144, 1084–1089.

    PubMed  Article  CAS  Google Scholar 

  • Odh, G., Hindemith, A., Rosengren, A.M., Rosengren, E. and Rorsman, H. (1993) Isolation of a new tautomerase monitored by the conversion of D-dopachrome to 5,6-dihydroxyindole.Biochem. Biophys. Res. Commun., 1993,197, 619–624.

    Article  CAS  Google Scholar 

  • Odh, C, Carstam, R., Paulson, J., Wittbjer, A., Rosengren, E. and Rorsman, H. (1994) Neuromelanin of the human substantia nigra: A mixed-type melanin.J. Neurochem.,62, 2030–2036.

    PubMed  CAS  Article  Google Scholar 

  • Offen, D., Ziv, I., Gorodin, S., Barzilay, A., Malik, Z. and Melamed, E. (1995) Dopamine-induced programmed cell death in mouse thymocytes.Biochim. Biophys. Acta,1268, 171–177.

    PubMed  Article  Google Scholar 

  • Offen, D., Ziv, I., Barzilai, A., Gorodin, S., Glater, E., Hochman, A. and Melamed, E. (1997) Dopamine-melanin induces apoptosis in PC12 cells; possible implications for the etiology of Parkinson’s disease.Neurochem. Int.,31, 207–216.

    PubMed  Article  CAS  Google Scholar 

  • Okun, M.R., Donnelan, B., Edelstein, L.M., Lever, W.F. and Or, N. (1971) Peroxidase-dependent oxidation of tyrosine and dopa to melanin in neurons.Histochimie,25, 289–296.

    PubMed  Article  CAS  Google Scholar 

  • Palumbo, A., D’Ischia, M., Misuraca, G., De Martino, L. and Prota, G. (1995) Iron and peroxide-dependent conjugation of dopamine with cysteine: oxidative routes to the novel brain metabolite 5-S-cysteinyldopamine.Biochim. Biophys. Acta,1245, 255–261.

    PubMed  Google Scholar 

  • Pawelek, J. and Lerner, A. (1978) 5,6-dihydroxyindole is a melanin precursor showing potent cytotoxicity.Nature,276, 627–628.

    Article  CAS  Google Scholar 

  • Pearce, R.K., Owen, A., Daniel, S., Jenner, P. and Marsden, CD. (1997) Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease.J. Neural. Transm.,104, 661–677.

    PubMed  Article  CAS  Google Scholar 

  • Prota, G. (1988) Progress in the chemistry of melanins and related metabolites.Med. Res. Rev.,8, 525–556.

    PubMed  Article  CAS  Google Scholar 

  • Prota, G. (1992)Melanin and Melanogenesis (Academic Press, San Diego, California).

    Google Scholar 

  • Prota, G., D’Ischia, M. and Napolitano, A. (1998). The chemistry of melanin and related metabolites (Chapter 24). In ‘The pigmentary system’. Oxford Univ. Press, pp. 307–332.

  • Rabey, J.M. and Hefti, F. (1990) Neuromelanin synthesis in rat and human substantia nigra.J. Neural. Transm. Park. Dis. Dement. Sect.,2, 1–14.

    PubMed  Article  CAS  Google Scholar 

  • Reiderer, P., Sofic, E., Rausch, W.D., Schmidt, B., Reynolds, G.P., Jellinger, K. and Youdum, M.B.H. (1989) Transition metals, ferritin, glutathione and ascorbic acid in Parkinsonian brain.J. Neurochem.,52, 515–520.

    Article  Google Scholar 

  • Reinemer, P., Dirr, H.W., Ladenstein, R., Schaffer, J., Gallay, O. and Huber, R. (1991) The three-dimensional structure of class Pi glutathione-S-transferase in complex with glutathione sulfonate at 2.3a resolution.EMBO J.,10, 1997–2005.

    PubMed  CAS  Google Scholar 

  • Riley, P.A. (1992) Materia melanica: Further Dark Thoughts.Pigment Cell Res.,5, 101–106.

    PubMed  Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Rosengren, E., Bucala, R., Arnan, P., Jacobsson, L., Odh, G., Metz, C.N. and Rorsman, H. (1996) The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction.Mol. Med.,2, 143–149.

    PubMed  CAS  Google Scholar 

  • Salazar, M., Sokoloski, T.D. and Patil, P.N. (1978) Binding of dopaminergic drugs by the neuromelanin of the substantia nigra, synthetic melanins and melanin granules.Fed. Proc,36, 2403–2407.

    Google Scholar 

  • Salinas, C, Garcia-Borron, J.C, Solano, F. and Lozano, J.A. (1994) Dopachrome tautomerase decreases the binding of indolic melanogenesis intermediates to proteins.Biochim. Biophys. Acta,1204, 53–60.

    PubMed  CAS  Google Scholar 

  • Schultzberg, M., Segura-Aguilar, J. and Lind, C. (1988) Distribution of DT-diaphorase in the rat brain: biochemical and immunohistochemical studies.Neuroscience,27, 55–57.

    Article  Google Scholar 

  • Segura-Aguilar, J., Baez, S., Widersten, M., Welch, C.J. and Mannervik, B. (1997) Human class Mu glutathione transferase, in particular isoenzyme M2-2, catalyze detoxification of the dopamine metabolite aminochrome.J. Biol. Chetn.,272, 5727–5731.

    Article  CAS  Google Scholar 

  • Smythies, J. (1996). On the function of neuromelanin.Proc. R. Soc. London B,263, 491–496.

    Article  Google Scholar 

  • Smythies, J. and Galzigna, L. (1998) The oxidative metabolism of catecholamines in the brain: a review.Biochim. Biophys. Acta,1380, 159–162.

    PubMed  CAS  Google Scholar 

  • Solano, F. (1993). Biochemistry of mammalian pigmentation: enzymatic regulation of melanogenesis. In ‘Cell and Tissue Culture Models in Dermatological Research’ (1993) (Bernd, A., Bereiter-Hahn, J., Hevert, F. and Holzmann, H. Eds.) Springer-Verlag, Berlin, pp. 135–147.

    Google Scholar 

  • Spina, M.B. and Cohen, G. (1989) Dopamine turnover and glutathione oxidation: Implications for Parkinson disease.Proc. Natl. Acad. Sci. USA,86, 1398–1400.

    PubMed  Article  CAS  Google Scholar 

  • Steel, K.P., Davidson, D.R. and Jackson, I.J. (1992) TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (C-kit ligand) is a survival factor.Development,115, 1111–1119.

    PubMed  CAS  Google Scholar 

  • Sun, H.W., Bernhagen, J., Bucala, R. and Lolis, E. (1996) Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor.Proc. Natl. Acad. Sci. USA,93, 5191–5196.

    PubMed  Article  CAS  Google Scholar 

  • Suzuki, M, Sugimoto, H., Tanaka, I. and Nishihira, J. (1997) Substrate specificity for isomerase activity of macrophage migration inhibitory factor and its inhibition by indole derivatives.J. Biochem (Tokyo),122, 1040–1045.

    CAS  Google Scholar 

  • Tief, K., Hahne, M., Schmidt, A. and Beermann, F. (1996) Tyrosinase, the key enzyme in melanin synthesis, is expressed in murine brain.Eur. J. Biochem.,241, 12–16.

    PubMed  Article  CAS  Google Scholar 

  • Tief, K., Schmidt, A. and Beermann, F. (1998) New evidences for the presence of tyrosinase in substantia nigra, forebrain and midbrain.Brain Res. Mol. Brain Res.,53, 307–310.

    PubMed  Article  CAS  Google Scholar 

  • Tsukamoto, K., Jackson, I.J., Urabe, K., Montague, P. and Hearing, V. (1992) A second tyrosinase related protein, TRP-2, is a melanogenic enzyme termed dopachrome tautomerase.EMBO J.,11, 519–526.

    PubMed  CAS  Google Scholar 

  • Urabe, K., Aroca, P., Tsukamoto, K., Mascagna, D., Palumbo, A., Prota, G. and Hearing, V.J. (1994) The inherent cytotoxicity of melanin precursors: a revision.Biochim. Biophys. Acta,1221, 272–278.

    PubMed  Article  CAS  Google Scholar 

  • Wakamatsu, K., Ito, S. and Nagatsu, T. (1991) Cysteinyldopamine is not incorporated into neuromelanin.Neuroscience Lett.,131, 57–60.

    Article  CAS  Google Scholar 

  • Wilczok, T, Stepien, K., Dzierzega-Lecznar, A., Zajdel, A. and Wilzok, A. (1998) Model neuromelanin as antioxidative agents during lipid peroxidation.INABIS’98 Internet World Congress, Neuroscience Section.

  • Youdim, M.B., Ben-Shachar, D. and Riederer, P. (1989) Is Parkinson’s disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration?.Acta Neurol. Scand.,126, 47–57.

    Article  CAS  Google Scholar 

  • Zareba, M., Bober, A., Korytowski, W., Zecca, L. and Sarna, T. (1995) The effect of a synthetic neuromelanin on yield of free hydroxyl radicals generated in model systems.Biochim. Biophys. Acta,1271, 343–348.

    PubMed  Google Scholar 

  • Zecca, L., Pietra, R., Goj, C, Mecacci, C, Radice, D. and Sabbioni, E. (1994) Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain.J. Neurochem., 1097–1101.

  • Zhang, F. and Dryhurst, G. (1994) Effects of L-cysteine and cysteinyl derivatives with dopamine-o-quinone and further insight into the oxidation chemistry of 5-S-cysteinyldopa-mine-potential relevance to idiopathic Parkinson’s disease.J. Med. Chem.,37, 1084–1098.

    PubMed  Article  CAS  Google Scholar 

  • Zhang, M., Aman, P., Grubb, A., Panagiopoulos, I., Hindemith, A., Rosengren, E. and Rorsman, H. (1995) Cloning and sequencing of a cDNA encoding rat D-dopa-chrome tautomerase.FEBS Lett.,373, 203–206.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Biochemistry and Molecular Biology B and Immunology, School of Medicine, University of Murcia, Apt. 4021, Campus de Espinardo, 30071, Murcia, Spain

    Francisco Solano & Jose C. García-Borrón

  2. Laboratory of Cell Biology, National Cancer Institute, NIH, 20892, MD, USA

    Vincent J. Hearing

Authors
  1. Francisco Solano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent J. Hearing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jose C. García-Borrón
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francisco Solano.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Solano, F., Hearing, V.J. & García-Borrón, J.C. Neurotoxicity due to o-Quinones: Neuromelanin formation and possible mechanisms for o-Quinone detoxification. neurotox res 1, 153–169 (1999). https://doi.org/10.1007/BF03033287

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033287

Keywords

  • o-Quinone
  • Neurotoxicity
  • Neuromelanin
  • Detoxification
  • Dopaquinone
  • Dopachrome
  • Catecholamines
  • Catecholaminechromes