Elevation of oxidized DJ-1 in the brain and erythrocytes of Parkinson disease model animals.
DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been reported undergo oxidation preferentially at the 106th cysteine residue (Cys-106) under oxidative stress. Recently, it has been found that the levels of oxidized DJ-1 in erythrocytes of unmedicated PD patients are markedly higher than those in medicated PD patients and healthy subjects. In the present study, we examined the changes in oxidized DJ-1 levels in the brain and erythrocytes of PD animal models using specific antibodies against Cys-106-oxidized DJ-1. Treatment with PD model compounds such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine significantly elevated the levels of oxidized DJ-1 in erythrocytes. Immunohistochemical analysis also revealed that the number of oxidized DJ-1 antibody-positive cells in the substantia nigra of MPTP-treated mouse increased in a dose-dependent manner. These results suggest that the oxidative modification of DJ-1 in the brain and erythrocytes is involved in the pathogenesis of PD in animal models.
Akazawa
Yoko Ogawa
YO
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, Japan.
Saito
Yoshiro
Y
Hamakubo
Takao
T
Masuo
Yoshinori
Y
Yoshida
Yasukazu
Y
Nishio
Keiko
K
Shichiri
Mototada
M
Miyasaka
Tomohiro
T
Iwanari
Hiroko
H
Mochizuki
Yasuhiro
Y
Kodama
Tatsuhiko
T
Noguchi
Noriko
N
Niki
Etsuo
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D051381:Rats; D013997:Time Factors
D002395:Catecholamines; D015513:Oncogene Proteins; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1