Abstract
Loss of function mutations of Park7/DJ-1 gene increase the susceptibility of dopaminergic cells to reactive oxygen species and cause early onset familial Parkinson disease (PD). However, the mechanisms underlying dopaminergic neuron loss related to DJ-1 mutation remain undefined. Therefore, it is important to find the new mechanisms underlying the antioxidative functions of DJ-1. Methods: DJ-1 knockdown cells and DJ-1 knockout mice were used to elucidate the mechanisms underlying the antioxidative stress of DJ-1. Preliminary study of the saliva from PD patients and controls was used to confirm our findings obtained from the above studies. Results: Our experiments showed that DJ-1 interacted with Erk1/2 and was required for the nuclear translocation of Erk1/2 upon oxidative stimulation. The translocation of Erk1/2 activated Elk1 and sequentially promoted superoxide dismutase1 (SOD1) expression. The nuclear translocation of Erk1/2, the activation of Elk1, and the ensuing upregulation of SOD1 were all suppressed in DJ-1 knockdown cells and DJ-1 null mice treated with oxidative insult. Furthermore, reintroduction of SOD1 into DJ-1 knockdown cells protected them against oxidative stress. Finally, in the preliminary study, we found close correlation between the protein levels of DJ-1 and SOD1 in the saliva samples from different stages of PD patients. Interpretation: Our studies suggest that DJ-1 regulates SOD1 expression through Erk1/2-Elk1 pathway in its protective response to oxidative insult.
Original language | English (US) |
---|---|
Pages (from-to) | 591-599 |
Number of pages | 9 |
Journal | Annals of neurology |
Volume | 70 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2011 |
ASJC Scopus subject areas
- Neurology
- Clinical Neurology