Distribution of oxidized DJ-1 in Parkinson's disease-related sites in the brain and in the peripheral tissues: effects of aging and a neurotoxin.

ABSTRACT

DJ-1 plays an important role in antioxidant defenses, and a reactive cysteine at position 106 (Cys106) of DJ-1, a critical residue of its biological function, is oxidized under oxidative stress. DJ-1 oxidation has been reported in patients with Parkinson's disease (PD), but the relationship between DJ-1 oxidation and PD is still unclear. In the present study using specific antibody for Cys106-oxidized DJ-1 (oxDJ-1), we analyzed oxDJ-1 levels in the brain and peripheral tissues in young and aged mice and in a mouse model of PD induced using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). OxDJ-1 levels in the brain, heart, and skeletal muscle were high compared with other tissues. In the brain, oxDJ-1 was detected in PD-related brain sites such as the substantia nigra (SN) of the midbrain, olfactory bulb (OB), and striatum. In aged wild-type mice, oxDJ-1 levels in the OB, striatum, and heart tended to decrease, while those in the skeletal muscle increased significantly. Expression of dopamine-metabolizing enzymes significantly increased in the SN and OB of aged DJ-1-/- mice, accompanied by a complementary increase in glutathione peroxidase 1. MPTP treatment concordantly changed oxDJ-1 levels in PD-related brain sites and heart. These results indicate that the effects of physiological metabolism, aging, and neurotoxin change oxDJ-1 levels in PD-related brain sites, heart, and skeletal muscle where mitochondrial load is high, suggesting a substantial role of DJ-1 in antioxidant defenses and/or dopamine metabolism in these tissues.