Oxidized metabolites of dopamine known as dopamine quinone derivatives are thought to play a pivotal role in the degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease. Although such quinone derivatives are usually produced via the autoxidation of catecholamines, tyrosinase, which is a key enzyme in melanin biosynthesis via the production of DOPA and subsequent molecules, can potentially accelerate the induction of catecholamine quinone derivatives by its oxidase activity. We have developed neuronal cell lines in which the expression of human tyrosinase was inducible. Overexpression of tyrosinase resulted in increased intracellular dopamine content in association with the formation of melanin pigments in neuronal somata, which eventually causes apoptotic cell death. This cellular model will provide a useful tool for detailed analyses of the neurotoxicity of oxidized catechol metabolites.
References
[1]
Sayre, LM; Smith, MA; Perry, G. Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr. Med. Chem？2001, 8, 721–738.
[2]
Jenner, P. Oxidative stress in Parkinson's disease. Ann Neurol？2003, 53(Suppl 3), S26–S36.
[3]
Kikuchi, A; Takeda, A; Onodera, H; Kimpara, T; Hisanaga, K; Sato, N; Nunomura, A; Castellani, RJ; Perry, G; Smith, MA; Itoyama, Y. Systemic increase of oxidative nucleic acid damage in Parkinson's disease and multiple system atrophy. Neurobiol. Dis？2002, 9, 244–248.
[4]
Cavalieri, EL; Li, KM; Balu, N; Saeed, M; Devanesan, P; Higginbotham, S; Zhao, J; Gross, ML; Rogan, EG. Catechol ortho-quinones: The electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis？2002, 23, 1071–1077.
[5]
Ben-Shachar, D; Zuk, R; Glinka, Y. Dopamine neurotoxicity: Inhibition of mitochondrial respiration. J. Neurochem？1995, 64, 718–723.
[6]
Stokes, AH; Hastings, TG; Vrana, KE. Cytotoxic and genotoxic potential of dopamine. J. Neurosci. Res？1999, 55, 659–665.
[7]
Smythies, J; Galzigna, L. The oxidative metabolism of catecholamines in the brain: A review. Biochim. Biophys. Acta？1998, 1380, 159–162.
[8]
Xu, Y; Stokes, AH; Roskoski, R; Vrana, KE. Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. J. Neurosci. Res？1998, 54, 691–697.
[9]
Bolton, JL; Trush, MA; Penning, TM; Dryhurst, G; Monks, TJ. Role of quinones in toxicology. Chem. Res. Toxicol？2000, 13, 135–160.
[10]
Asanuma, M; Miyazaki, I; Ogawa, N. Dopamine- or l-DOPA-induced neurotoxicity: The role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease. Neurotox Res？2003, 5, 165–176.
Conway, KA; Rochet, JC; Bieganski, RM; Lansbury, PT. Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science？2001, 294, 1346–1349.
[13]
Norris, EH; Giasson, BI; Hodara, R; Xu, S; Trojanowski, JQ; Ischiropoulos, H; Lee, VM. Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome-mediated conformational alterations. J. Biol. Chem？2005, 280, 21212–21219.
[14]
Paris, I; Cardenas, S; Lozano, J; Perez-Pastene, C; Graumann, R; Riveros, A; Caviedes, P; Segura-Aguilar, J. Aminochrome as a preclinical experimental model to study degeneration of dopaminergic neurons in Parkinson's disease. Neurotox. Res？2007, 12, 125–134.
[15]
Robb, DA. Tyrosinase; CRC Press: Boca Raton, FL, USA, 1984; Volume 2, pp. 207–241.
[16]
Korner, A; Pawelek, J. Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science？1982, 217, 1163–1165.
[17]
Sanchez-Ferrer, A; Rodriguez-Lopez, JN; Garcia-Canovas, F; Garcia-Carmona, F. Tyrosinase: A comprehensive review of its mechanism. Biochim. Biophys. Acta？1995, 1247, 1–11.
[18]
Miranda, M; Botti, D; Bonfigli, A; Ventura, T; Arcadi, A. Tyrosinase-like activity in normal human substantia nigra. Gen. Pharmacol？1984, 15, 541–544.
[19]
Miranda, M; Botti, D. Harding-passey mouse-melanoma tyrosinase inactivation by reaction products and activation by L-epinephrine. Gen. Pharmacol？1983, 14, 231–237.
[20]
Takeda, A; Tomita, Y; Matsunaga, J; Tagami, H; Shibahara, S. Molecular basis of tyrosinase-negative oculocutaneous albinism. A single base mutation in the tyrosinase gene causing arginine to glutamine substitution at position 59. J. Biol. Chem？1990, 265, 17792–17797.
[21]
Zecca, L; Tampellini, D; Gerlach, M; Riederer, P; Fariello, RG; Sulzer, D. Substantia nigra neuromelanin: Structure, synthesis, and molecular behaviour. Mol. Pathol？2001, 54, 414–418.
[22]
Xu, Y; Stokes, AH; Freeman, WM; Kumer, SC; Vogt, BA; Vrana, KE. Tyrosinase mRNA is expressed in human substantia nigra. Brain Res. Mol. Brain Res？1997, 45, 159–162.
[23]
Tief, K; Schmidt, A; Beermann, F. New evidence for presence of tyrosinase in substantia nigra, forebrain and midbrain. Brain Res. Mol. Brain Res？1998, 53, 307–310.
[24]
Greggio, E; Bergantino, E; Carter, D; Ahmad, R; Costin, GE; Hearing, VJ; Clarimon, J; Singleton, A; Eerola, J; Hellstrom, O; Tienari, PJ; Miller, DW; Beilina, A; Bubacco, L; Cookson, MR. Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease. J. Neurochem？2005, 93, 246–256.
[25]
Hasegawa, T; Matsuzaki-Kobayashi, M; Takeda, A; Sugeno, N; Kikuchi, A; Furukawa, K; Perry, G; Smith, MA; Itoyama, Y. Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: Implications for selective neurodegeneration in Parkinson's disease. FEBS Lett？2006, 580, 2147–2152.
[26]
Hasegawa, T; Matsuzaki, M; Takeda, A; Kikuchi, A; Furukawa, K; Shibahara, S; Itoyama, Y. Increased dopamine and its metabolites in SH-SY5Y neuroblastoma cells that express tyrosinase. J. Neurochem？2003, 87, 470–475.
[27]
Hasegawa, T; Treis, A; Patenge, N; Fiesel, FC; Springer, W; Kahle, PJ. Parkin protects against tyrosinase-mediated dopamine neurotoxicity by suppressing stress-activated protein kinase pathways. J. Neurochem？2008, 105, 1700–1715.
[28]
Hasegawa, T; Sugeno, N; Takeda, A; Matsuzaki-Kobayashi, M; Kikuchi, A; Furukawa, K; Miyagi, T; Itoyama, Y. Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites. FEBS Lett？2007, 581, 406–412.
[29]
Halaban, R; Cheng, E; Zhang, Y; Moellmann, G; Hanlon, D; Michalak, M; Setaluri, V; Hebert, DN. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proc. Natl. Acad. Sci. USA？1997, 94, 6210–6215.
[30]
Setaluri, V. Sorting and targeting of melanosomal membrane proteins: Signals, pathways, and mechanisms. Pigment Cell Res？2000, 13, 128–134.
[31]
Toyofuku, K; Wada, I; Hirosaki, K; Park, JS; Hori, Y; Jimbow, K. Promotion of tyrosinase folding in COS 7 cells by calnexin. J. Biochem. (Tokyo)？1999, 125, 82–89.
[32]
Orlow, SJ. Melanosomes are specialized members of the lysosomal lineage of organelles. J. Invest. Dermatol？1995, 105, 3–7.
[33]
Simmen, T; Schmidt, A; Hunziker, W; Beermann, F. The tyrosinase tail mediates sorting to the lysosomal compartment in MDCK cells via a di-leucine and a tyrosine-based signal. J Cell Sci？1999, 112, 45–53.
[34]
Tribl, F; Marcus, K; Meyer, HE; Bringmann, G; Gerlach, M; Riederer, P. Subcellular proteomics reveals neuromelanin granules to be a lysosome-related organelle. J. Neural. Transm？2006, 113, 741–749.
[35]
Vijayasaradhi, S; Xu, Y; Bouchard, B; Houghton, AN. Intracellular sorting and targeting of melanosomal membrane proteins: identification of signals for sorting of the human brown locus protein, gp75. J. Cell Biol？1995, 130, 807–820.
[36]
Singh, MV; Jimbow, K. Tyrosinase transfection produces melanin synthesis and growth retardation in glioma cells. Melanoma Res？1998, 8, 493–498.
[37]
Bouchard, B; Fuller, BB; Vijayasaradhi, S; Houghton, AN. Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. J. Exp. Med？1989, 169, 2029–2042.
[38]
Yamamoto, H; Takeuchi, S; Kudo, T; Sato, C; Takeuchi, T. Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA. Jpn. J. Genet？1989, 64, 121–135.
