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.

Natrium Benzoate Alleviates Neuronal Apoptosis via the DJ-1-Related Anti-oxidative Stress Pathway Involving Akt Phosphorylation in a Rat Model of Traumatic Spinal Cord Injury

“…Additionally, excessive oxDJ-1 enables cells to commit to apoptosis (Cao et al, 2014). In patients and animal models of PD, oxDJ-1 was increased in unmedicated PD, while drug therapy lowered oxDJ-1 levels, suggesting oxDJ-1 played an important role in PD and was a potential biomarker for PD (Saito, 2014; Saito et al, 2014; Mita et al, 2018; Yamagishi et al, 2018). Thus, we also tested the expression of oxDJ-1 and found that oxDJ-1 was significantly increased after t-SCI induction.…”

The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson’s Disease

“…The recessive PD gene FBXO7 encodes a component of the E3 Ub ligase, the reduced expression of which leads to deficient parkin translocation to damaged mitochondria, decreased Mfn ubiqutination, and impaired mitophagy [108]. The loss of function mutations of the DJ-1 gene is associated with recessive early-onset familial PD and late-onset sporadic PD [109]. The gene encodes the 189-amino-acid DJ-1 protein, with studies having demonstrated greater DJ-1 oxidative damage and elevated DJ-1 protein levels in postmortem brains of sporadic PD patients [110].…”

IL‐1β/IL‐1R1 signaling induced by intranasal lipopolysaccharide infusion regulates alpha‐Synuclein pathology in the olfactory bulb, substantia nigra and striatum

“…The OB, SN and striatum tissues of the brain were removed in icecold conditions and stored at −80°C until further use. The methods for brain dissection have been described previously (38). The OB, SN and striatum tissues were then used for Western blot.…”