DJ-1 modulates the expression of Cu/Zn-superoxide dismutase-1 through the Erk1/2–Elk1 pathway in neuroprotection
Article first published online: 27 JUL 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 4, pages 591–599, October 2011
How to Cite
Wang, Z., Liu, J., Chen, S., Wang, Y., Cao, L., Zhang, Y., Kang, W., Li, H., Gui, Y., Chen, S. and Ding, J. (2011), DJ-1 modulates the expression of Cu/Zn-superoxide dismutase-1 through the Erk1/2–Elk1 pathway in neuroprotection. Ann Neurol., 70: 591–599. doi: 10.1002/ana.22514
- Issue published online: 25 OCT 2011
- Article first published online: 27 JUL 2011
- Accepted manuscript online: 7 JUN 2011 01:18PM EST
- Manuscript Accepted: 2 JUN 2011
- Manuscript Revised: 23 MAY 2011
- Manuscript Received: 20 JUL 2010
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.
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.
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.
Our studies suggest that DJ-1 regulates SOD1 expression through Erk1/2–Elk1 pathway in its protective response to oxidative insult. ANN NEUROL 2011