Advanced SearchSearch Tips
Oxidative modification of human ceruloplasmin induced by a catechol neurotoxin, salsolinol
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 49, Issue 1,  2016, pp.45-50
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.1.103
 Title & Authors
Oxidative modification of human ceruloplasmin induced by a catechol neurotoxin, salsolinol
Kim, Seung-Sub; Kang, Jae Yoon; Kang, Jung Hoon;
  PDF(new window)
Salsolinol (SAL), a compound derived from dopamine metabolism, is the most probable neurotoxin involved in the pathogenesis of Parkinson's disease (PD). In this study, we investigated the modification and inactivation of human ceruloplasmin (hCP) induced by SAL. Incubation of hCP with SAL increased the protein aggregation and enzyme inactivation in a dose-dependent manner. Reactive oxygen species scavengers and copper chelators inhibited the SAL-mediated hCP modification and inactivation. The formation of dityrosine was detected in SAL-mediated hCP aggregates. Amino acid analysis post the exposure of hCP to SAL revealed that aspartate, histidine, lysine, threonine and tyrosine residues were particularly sensitive. Since hCP is a major copper transport protein, oxidative damage of hCP by SAL may induce perturbation of the copper transport system, which subsequently leads to deleterious conditions in cells. This study of the mechanism by which ceruloplasmin is modified by salsolinol may provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD. [BMB Reports 2016; 49(1): 45-50]
Ceruloplasmin;Copper;Reactive oxygen species;Salsolinol;
 Cited by
Olasode B, Niger JJ (2001) Idiopathic Parkinson's disease: a review of clinical types and pathology. Med 10, 116-120

Scott TR, Netsky MG (1961) The pathology of Parkinson's syndrome: a critical review. Int J Neurol 2, 51-60

Ikeda H, Markey CJ, Markey SP (1993) Search for neurotoxins structurally related to 1-methyl-4-phenylpyridine (MPP+) in the pathogenesis of Parkinson's disease. Brain Res 575, 285-298 crossref(new window)

Moser A, Kompf D (1992) Presence of methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines, derivatives of the neurotoxin isoquinoline, in parkinsonian lumbar CSF. Life Sciences 50, 1885-1891 crossref(new window)

Niwa T, Takeda T, Yoshizumi H et al (1991) Presence of 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoqui-noline and 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydro-isoquinoline, novel endogenous amines, in parkinsonian and normal human brains. Biochem Biophys Res Commun 177, 603-609 crossref(new window)

Ohta S, Kohno M, Makino Y et al (1987) Tetrahydroisoquinoline and 1-methyl-tetrahydroisoquinoline are present in the human brain: relation to Parkinson's disease. Biomed Res 8, 453-456

Naoi M, Maruyama W, Akao Y and Yi H (2002) Dopamine-derived endogenous N-methyl-(R)-salsolinol: its role in Parkinson's disease. Neurotoxicol Teratol 24, 579-591 crossref(new window)

Naoi M, Marayama W, Dostert P et al (1996) A novel enzyme enantio-selectively synthesizes (R)salsolinol, a precursor of a dopaminergic neurotoxin, N-methyl(R)salsolinol. Neurosci Lett 212, 183-186 crossref(new window)

Deng Y, Luan Y, Qing H et al (2008) The formation of catechol isoquinolines in PC12 cells exposed to manganese. Neurosci Lett 444, 122-126 crossref(new window)

Jamal M, Ameno K, Ameno S et al (2003) In Vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats. Alcohol Clin Exp Res 27, 79S-84S crossref(new window)

Jamal M, Ameno K, Kubota T et al (2003) In vivo formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis. Alcohol Alcohol 38, 197-201 crossref(new window)

Wang R, Qing H, Liu XQ et al (2008) Iron contributes to the formation of catechol isoquinolines and oxidative toxicity induced by overdose dopamine in dopaminergic SH-SY5Y cells. Neurosci Bull 24, 125-132 crossref(new window)

Mravec B (2006) Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments. Physiol Res 55, 353-364

Wanpen S, Govitrapong P, Shavali S et al (2004) Salsolinol, a dopamine-derived tetrahydroisoquinoline, induces cell death by causing oxidative stress in dopaminergic SH-SY5Y cells, and the said effect is attenuated by metallothionein. Brain Res 1005, 67-76 crossref(new window)

Kang JH (2013) Salsolinol, a catechol neurotoxin, induces oxidative modification of cytochrome c. BMB Rep 46, 119-123 crossref(new window)

Kang JH (2007) Salsolinol, a tetrahydroisoquinoline catechol neurotoxin, induces human Cu,Zn-superoxidie dismutase modificaiton. J Biochem Mol Biol 40, 684-689 crossref(new window)

Rouault TA and Cooperman S (2006) Brain iron metabolism. Semin Padiatr Neurol 13, 142-148 crossref(new window)

Harris ZL, Takahashi Y, Miyajima H et al (1995) Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc Natl Acad Sci U S A 92, 2539-2543 crossref(new window)

Kim KS, Choi SY, Kwon HY et al (2002) The ceruloplasmin and hydrogen peroxide system induces alpha-synuclein aggregation in vitro. Biochimie 84, 625-631 crossref(new window)

Boll MC (2008) Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases. Neurochem Res 33, 1717-1723 crossref(new window)

Boll MC, Sotelo J, Otero E et al (1999) Reduced ferroxidase activity in the cerebrospinal fluid from patients with Parkinson's disease. Neurosci lett 265, 155-158 crossref(new window)

Olivieri S, Conti A, Iannaccone S et al (2011) Ceruloplasmin oxidation, a feature of Parkinson's disease CSF, inhibits ferroxidase activity and promotes cellular iron retention. J Neurosci 31, 18568-18577 crossref(new window)

Martinez-Hemandez R, Montes S, Higuera-Calleja J et al (2011) Plasma ceruloplasmin ferroxidase activity correlates with the nigral sonographic area in Parkinson's disease patients: a pilot study. Neurochem Res 36, 2111-2115 crossref(new window)

Bharucha KJ, Friedman JK, Vincent AS and Ross ED (2008) Lower serum ceruloplasmin levels correlate with younger age of onset in Parkinson's disease. J Neurol 255, 1957-1962 crossref(new window)

Torsdottir G, kristinsson J, Sveinbjornsdottir S et al (1999) Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharmacol Toxical 85, 239-243 crossref(new window)

Jin L, Wang J, Zhao L et al (2011) Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson's disease. Brain 134, 50-58 crossref(new window)

Jin L, Wang J, Jin H et al (2012) Nigral iron deposition occurs across motor phenotypes of Parkinson's disease. Eur J Neurol 19, 969-976 crossref(new window)

Torsdottir G, Sveinbjornsdottir S, Kristinsson J et al (2006) Ceruloplasmin and superoxide dismutase (SOD1) in Parkinson's disease: a follow-up study. J Neurol Sci 241, 53-58 crossref(new window)

Osaki S, Johnson DA and Frieden E (1966) The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. J Boil Chem 241, 2746-2751

Levine RL, Williams JA, Stadtman ER and Shacter E (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 233, 346-357 crossref(new window)

Kang JH (2004) Modification of Cu,Zn-superoxide dismutase by oxidized catecholamines. J Biochem Mol Biol 37, 325-329 crossref(new window)

Kim SM and Kang JH (1997) Peroxidative activity of human Cu,Zn-superoxide dismutase. Mol Cells 7, 120-124

Choi SY, Kwon HY, Kwon OB and Kang JH (1999) Hydrogen peroxide-mediated Cu,Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine. Biochim Biophys Acta 1472, 651-657 crossref(new window)

Halliwell B and Gutteridge JMC (2007) Free Radicals in Biology and Medicine, Oxford, New York.

Davies KJ, Delsignore ME and Lin SW (1987) Protein damage and degradation by oxygen radicals. II. Modification of amino acids. J Biol Chem 262, 9902-9907

Goldstein S and Czapski G (1987) Mechanism of reduction of bleomycin-Cu(II) by CO2- and oxidation of bleomycin-Cu(I) by H2O2 in the absence and presence of DNA. Int J Radiation Biol Related Stud Phys Chem Med 51, 693-706 crossref(new window)

Gutteridge JM and Halliwell B (1982) The role of the superoxide and hydroxyl radicals in the degradation of DNA and deoxyribose induced by a copper-phenanthroline complex. Biochem Pharmacol 31, 2801-2805 crossref(new window)

Imlay JA, Chin SM and Linn S (1988) Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240, 640-642 crossref(new window)

Schweigert N, Zehnder AJ and Eggen RI (2001) Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. Environ Microbiol 3, 81-91 crossref(new window)

Li Q, Aubrey MT, Christion T and Free BM (1997) Differential inhibition of DNA synthesis in human T cells by the cigarette tar components hydroquinone and catechol. Fundam Appl Toxicol 38, 158-165 crossref(new window)

Zaitseva I, Zaitsev V, Card G et al (1996) The X-ray structure of human serum ceruloplasmin at 3.1 Å: nature of the copper centres. J Biol Inorg Chem 1, 15-23 crossref(new window)

Malmstom BG (1982) Enzymology of oxygen. Ann Rev Biochem 51, 21-59 crossref(new window)

Bento I, Peixoto C, Zaisev VN and Lindley PF (2007) Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites. Acta Cryst 63, 240-248

Choi SY, Kwon HY, Kwon OB et al (2000) Fragmentation of human ceruloplasmin induced by hydrogen peroxide. Biochimie 82, 175-180 crossref(new window)

Kang JH, Kim KS, Choi SY et al (2001) Oxidative modification of human ceruloplasmin by peroxyl radicals. Biochim Biophys Acta 1568, 30-36 crossref(new window)

Montes S, Rivera-Mancia S, Diaz-Ruiz A, Tristan-Lopez L and Rios C (2014) Copper and copper proteins in Parkinson's disease. Oxid Med Cell Longev 2014, 147251-147266 crossref(new window)

Surh YJ, Jung YJ, Jung JH, Lee JS and Yoon HR (2002) Iron enhancement of oxidative DNA damage and neuronal cell death induced by salsolinol. J Toxicol Environ Health Part A 65, 473-488 crossref(new window)

Jung YJ and Surh YJ (2001) Oxidative DNA damage and cytotoxicity induced by copper-stimulated redox cycling of salsolinol, a neurotoxic tetrahydroisoquinoline alkaloid. Free Radic Biol Med 30, 1407-1417 crossref(new window)

Wanpen S, Govitrapong P, Shavali S, Sangchot PM and Ebadi M (2004) Salsolinol, a dopamine-derived tetrahydroisoquinoline, induces cell death by causing oxidative stress in dopaminergic SH-SY5Y cells, and the said effect is attenuated by metallothionein. Brain Res 1005, 67-76 crossref(new window)

Maruyama W, Sobuc G, Matsubara K et al (1997) A dopaminergic neurotoxin, 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydro-isoquinoline, N-methyl(R)salsolinol, and its oxidation product, 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion, accumulate in the nigro-striatal system of the human brain. Neurosci Lett 223, 61-64 crossref(new window)

Maruyama W, Abe T, Tohgi H, Dostert P and Naoi M (1996) A dopaminergic neurotoxin, (R)-N-methylsalsolinol, increases in Parkinsonian cerebrospinal fluid. Ann Neurol 40, 119-122 crossref(new window)

Smith PK, Krohn RI, Hermanson GT et al (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150, 76-85 crossref(new window)

Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685 crossref(new window)

Sato M, Gitlin JD (1991) Mechanisms of copper incorporation during the biosynthesis of human ceruloplasmin. J Biol Chem 266, 5128-5134

Kang JH (2013) Modification and inactivation of Cu,Zn-superoxidee dismutase. BMB Rep 46, 555-560 crossref(new window)

Levine RL (1982) Rapid benchtop method of alkaline hydrolysis of proteins. J Chromatogr 236, 496-498 crossref(new window)