title: DJ-1 modulates the expression of Cu/Zn-superoxide dismutase-1 through the Erk1/2-Elk1 pathway in neuroprotection.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our studies suggest that DJ-1 regulates SOD1 expression through Erk1/2-Elk1 pathway in its protective response to oxidative insult.
authors.affiliation: Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Siyan
authors.initials: S
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenyan
authors.initials: W
authors.lastname: Kang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Gui
authors.forename: Shengdi
authors.initials: S
authors.lastname: Chen
authors.forename: Jianqing
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D012463:Saliva / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014162:Transfection; D014178:Translocation, Genetic; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C494112:ELK1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D050807:ets-Domain Protein Elk-1; D013482:Superoxide Dismutase; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1