A role for the Parkinson’s disease protein DJ-1 as a chaperone and antioxidant in the anhydrobiotic nematode Panagrolaimus superbus

Abstract

Mutations in the human DJ-1/PARK7 gene are associated with familial Parkinson's disease. DJ-1 belongs to a large, functionally diverse family with homologues in all biological kingdoms. Several activities have been demonstrated for DJ-1: an antioxidant protein, a redoxregulated molecular chaperone and a modulator of multiple cellular signalling pathways. The majority of functional studies have focussed on human DJ-1 (hDJ-1), but studies on DJ-1 homologues in Drosophila melanogaster, Caenorhabditis elegans, Dugesia japonica and Escherichia coli also provide evidence of a role for DJ-1 as an antioxidant. Here, we show that dehydration is a potent inducer of a dj-1 gene in the anhydrobiotic nematode Panagrolaimus superbus. Our secondary structure and homology modelling analyses shows that recombinant DJ-1 protein from P. superbus (PsuDJ-1.1) is a well-folded protein, which is similar in structure to the hDJ-1. PsuDJ-1.1 is a heat stable protein; with T 1/2 unfolding transition values of 76 and 70°C obtained from both circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) measurements respectively. We found that PsuDJ-1.1 is an efficient antioxidant that also functions as a 'holdase' molecular chaperone that can maintain its chaperone function in a reducing environment. In addition to its chaperone activity, PsuDJ-1.1 may also be an important non-enzymatic antioxidant, capable of providing protection to P. superbus from oxidative damage when the nematodes are in a desiccated, anhydrobiotic state.

Multiple genes contribute to anhydrobiosis (tolerance to extreme desiccation) in the nematode Panagrolaimus superbus

“…Organisms have developed adaptive mechanisms for cellular detoxification, including systems that repair or prevent damage caused by oxidants ( Michiels et al ., 1994 ). Among such defense systems in the anhydrobiotic nematode Panagrolaimus superbus are: protein DJ-1 ( Culleton et al , 2015 ), glutathione peroxidases (GP114) and peroxiredoxin (PER).…”

Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2

“…DJ-1 was first identified as an oncogene (2) and has since been described as a causative gene for early-onset Parkinson disease (3,4). Although DJ-1 has protease (5-7) or chaperone (8,9) activities, most studies have focused on its protective role against oxidative stress (10 -15). Knock-out of the DJ-1 gene enhances hydrogen peroxide (H 2 O 2 ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated cell death.…”

Bifunctional Chloroplastic DJ-1B from Arabidopsis thaliana is an Oxidation-Robust Holdase and a Glyoxalase Sensitive to H2O2

“…Remarkably, we observed that the thermostability of AtDJ-1B increases upon oxidation, which indicates that the oxidized form of AtDJ-1B is more likely than reduced AtDJ-1B to retain its chaperone activity under sustained heat stress. Other DJ-1 family members have also been shown to be highly thermostable, with a T M values ranging from 64 to 77 °C [36,51,52]. Here, we determined a comparatively lower T M for AtDJ-1B of 59.7 °C, and observe an increase in T M of approximately 8–10 °C for oxidized AtDJ-1B.…”