Skip to main content

Model neuromelanins as antioxidative agents during lipid peroxidation

Abstract

The oxidative pathway of dopamine metabolism in the human brain leads to formation and accumulation of neuromelanin in the cytoplasm of most nigrostriatal dopaminergic neurons. The physiological significance of neuromelanin and its contribution to the neurodegenerative processes underlying Parkinson’s disease are still controversial.

The effect of model neuromelanins on Fe(II)/ascorbate-induced lipid peroxidation in micelles of linoleic acid and in lecithin liposomes was determined. Synthetic neuromelanins were obtained from dopamine (DA), 5-S-cysteinyldopamine (CysDA) or from equimolar mixture of these precursors. Thiobarbituric acid test and reverse-phase HPLC, used for measurements of primary and secondary oxidation products, showed that all melanins tested significantly suppressed peroxidation of both, linoleic acid and liposomal lecithin. The inhibitory effect of CysDA-melanin was lower than of DA/CysDA-melanin and DA-melanin. All the melanins were able to reduce linoleic acid hydroperoxides to their stable hydroxy derivatives. The results obtained suggest that neuromelanin can act as natural antioxidant. The fatty acid hydroperoxide-reducing ability demonstrated for the model neuromelanins appears to be involved in the mechanism of antioxidative activity of neuromelanin.

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

Reference

  • Bangham, A.D., Hill, M.W. and Miller, N.G.A. (1974) Preparation and use of liposomes as models of biological membranes. In:Methods in Membrane Biology (Ed. Korn, E.D.), Plenum Press, New York, London, pp. 1–68.

    Google Scholar 

  • Ben-Shachar, D., Riederer, P. and Youdim, M.B.H. (1991) Iron-melanin interaction and lipid peroxidation: implications for Parkinson’s disease.J. Neurochem. 57, 1609–1614.

    PubMed  Article  CAS  Google Scholar 

  • Buege, J. and Aust, S.D. (1978) Microsomal lipid peroxidation.Methods Enzymol. 52C, 302–310.

    Article  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 

  • Cheng, EC, Kuo, J.S., Chia, L.G. and Dryhurst, G. (1996) Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homo vanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson’s disease.J. Neural Transm. 103, 433–446.

    PubMed  Article  CAS  Google Scholar 

  • Dexter, D.T., Carter, C.J., Wells, F.R., Javoy-Agid, E, Agid, Y, Lees, A.J., Jenner, P. and Marsden, CD. (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease.J. Neurochem. 52, 381–389.

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Enochs, W.S., Sarna, T., Zecca, L., Riley, P.A. and Swartz, H.M. (1994) The roles of neuromelanin, binding of metal ions, and oxidative cytotoxicity in the pathogenesis of Parkinson’s disease: a hypothesis.J. Neural Transm. 7, 83–100.

    Article  CAS  Google Scholar 

  • Fahn, S. and Cohen, G. (1992) The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it.Ann. Neurol. 32, 804–812.

    PubMed  Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Gibian, M. and Vandenberg, P. (1987) Product yield in oxygenation of linoleate by soybean lipoxygenase: the value of the molar extinction coefficient in the spectrophotometric assay.Anal. Biochem. 163, 343–349.

    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. (1979) On the origin and significance of neuromelanin.Arch. Pathol. Lab. Med. 103, 359–362.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Ito, S., Fujita, K., Yoshioka, M., Sienko, D. and Nagatsu, T. (1986) Identification of 5-S- and 2-S-cysteinyldopamine and 5-S-glutathionyldopamine formed from dopamine by high-performance liquid chromatography with electrochemical detection.J. Chromatogr. 375, 134–140.

    Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Kastner, A., Hirsch, E.C., Lejeune, O., Javoy-Agid, E, 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.

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Marsden, C.D. (1983) Neuromelanin and Parkinson’s disease.J. Neural Transm. Suppl. 19, 121–141.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Odh, G., 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  Google Scholar 

  • Okun, M.R. (1997) The role of peroxidase in neuromelanin synthesis: a review.Physiol. Chem. Phys. Med. NMR 29, 15–22.

    PubMed  CAS  Google Scholar 

  • Porebska-Budny, M., Sakina, N.L., Stepien, K.B., Dontsov, A.E. and Wilczok, T. (1992) Antioxidative activity of synthetic melanins. Cardiolipin liposome model.Biochim. Biophys. Acta 1116, 11–16.

    PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Rodgers, A.D. and Curzon, G. (1975) Melanin formation by human brainin vitro.J. Neurochem. 24, 1123–1129.

    PubMed  Article  CAS  Google Scholar 

  • Rosei, M.A., Blarzino, C, Foppoli, C, Mosca, L. and Coccia, R. (1994) Lipoxygenase-catalyzed oxidation of catecholamines.Biochem. Biophys. Res. Commun. 200, 344–350.

    PubMed  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 

  • Shen, X.M. and Dryhurst, G. (1996) Further insights into the influence of L-cysteine on the oxidation chemistry of dopamine: reaction pathways of potential relevance to Parkinson’s disease.Chem. Res. Toxicol. 9, 751–763.

    PubMed  Article  CAS  Google Scholar 

  • Smythies, J. (1996) On the function of neuromelanin.Proc. R. Soc. Lond. B 263, 487–489.

    Article  CAS  Google Scholar 

  • Stepien, K. and Wilczok, T. (1994) Antioxidant activity of model neuromelanins in the process of lipid peroxidation.Current Topics Biophys. 18, 135–138.

    CAS  Google Scholar 

  • Stepien, K., Porebska-Budny, M., Hollek, A.M. and Wilczok, T. (1992) The inhibiting effect of catechola mine-melanins on UV-induced lecithin peroxidation.J. Photochem. Photobiol. B: Biol. 15, 223–231.

    Article  CAS  Google Scholar 

  • Stepien, K., Zajdel, A., Swierczek, G., Wilczok, A. and Wilczok, T. (1998) Reduction of 13-hydroperoxy-9,ll-octadecadienoic acid by dopamine-melanin.Biochem. Biophys. Res. Commun. 244, 781–784.

    PubMed  Article  CAS  Google Scholar 

  • Tse, D.C.S., McCreery, R.L. and Adams, R.N. (1976) Potential oxidative pathways of brain catecholamines.J. Med. Chem. 19, 37–40.

    PubMed  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., Shima, T., Stroppolo, A., Goj, C, Battiston, G.A., Gerbasi, R., Sarna, T. and Swartz, H.M. (1996) Interaction of neuromelanin and iron in substantia nigra and other areas of human brain.Neuroscience. 73, 407–415.

    PubMed  Article  CAS  Google Scholar 

  • Zhang, F. and Dryhurst, G. (1994) 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, 1084–1090.

    PubMed  Article  CAS  Google Scholar 

  • Zhang, F. and Dryhurst, G. (1995) Reactions of cysteine and cysteinyl derivatives with dopamine-o-quinone and further insights into the oxidation chemistry of 5-S-cysteinyldopamine: potential relevance to idiopathic Parkinson’s disease.Chem. Res. Toxicol. 9, 751–763.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Tadeusz Wilczok.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wilczok, T., Stepien, K., Dzierzega-Lecznar, A. et al. Model neuromelanins as antioxidative agents during lipid peroxidation. neurotox res 1, 141–147 (1999). https://doi.org/10.1007/BF03033277

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033277

Keywords

  • Lipid
  • Neuromelanin
  • Peroxidation