title: Oxidation and interaction of DJ-1 with 20S proteasome in the erythrocytes of early stage Parkinson's disease patients.
abstract: Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress. Here, using specific antibodies against Cys-106-oxidized DJ-1 (oxDJ-1), it was found that the levels of oxDJ-1 in the erythrocytes of unmedicated PD patients (n = 88) were higher than in those of medicated PD patients (n = 62) and healthy control subjects (n = 33). Elevated oxDJ-1 levels were also observed in a non-human primate PD model. Biochemical analysis of oxDJ-1 in erythrocyte lysates showed that oxDJ-1 formed dimer and polymer forms, and that the latter interacts with 20S proteasome. These results clearly indicate a biochemical alteration in the blood of PD patients, which could be utilized as an early diagnosis marker for PD.
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.|National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Akazawa-Ogawa
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Department of Neurology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Saigoh
authors.affiliation: Hamamatsu Pharma Research Inc., Hamamatsu 431-2103, Japan.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Itoh
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Sutou
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Mayuka
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mita
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Mototada
authors.initials: M
authors.lastname: Shichiri
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hisahara
authors.affiliation: Hara Clinic, Ikeda, Osaka 563-0025, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Department of Neurology, National Hospital Organization Toneyama National Hospital, Toyonaka, Osaka 560-8552, Japan.
authors.forename: Harutoshi
authors.initials: H
authors.lastname: Fujimura
authors.affiliation: Hamamatsu Pharma Research Inc., Hamamatsu 431-2103, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamatsu
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hagihara
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-0041, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.affiliation: Department of Neurology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
authors.affiliation: Department of Neurology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.affiliation: Systems Life Sciences laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Noguchi
mesh_terms: D000368:Aged; D000818:Animals; D003545:Cysteine / Q000737:chemistry; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1 / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D007980:Levodopa; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D046988:Proteasome Endopeptidase Complex; D003545:Cysteine