title: Oxidative modification of human ceruloplasmin induced by a catechol neurotoxin, salsolinol.
abstract: 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.
authors.affiliation: Department of Biomedical Science, Cheongju University, Cheongju 28160, Korea.
authors.forename: Seung-Sub
authors.initials: SS
authors.lastname: Kim
authors.affiliation: School of Interdisciplinary Studies, Korea University, Seoul 02841, Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Kang
authors.affiliation: Department of Biomedical Science, Cheongju University, Cheongju 28160, Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D002396:Catechols / Q000737:chemistry / Q000378:metabolism*; D002570:Ceruloplasmin / Q000737:chemistry / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D028561:Transition Elements / Q000737:chemistry / Q000378:metabolism
chemical_list: D002396:Catechols; D016166:Free Radical Scavengers; D007546:Isoquinolines; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D028561:Transition Elements; C036617:salsolinol; D002570:Ceruloplasmin; C034221:catechol