title: Proteomic analysis reveals a protective role for DJ-1 during 6-hydroxydopamine-induced cell death.
abstract: Loss-of-function mutations in the DJ-1/PARK7 gene are responsible for early-onset autosomal-recessive Parkinson's disease. DJ-1 is implicated in the protection of neurons from oxidative stress by scavenging hydrogen peroxide and regulating the transcriptional activity of multiple pathways. Here, we attempted to identify the protein profiles modulated by DJ-1 in MN9D dopaminergic neurons following 6-hydroxydopamine (6-OHDA) treatment. We found that reactive oxygen species (ROS) levels increased in DJ-1-deficient cells that were either untreated or subjected to 6-OHDA treatment. The incidence of apoptosis after 6-OHDA treatment was increased in DJ-1 knockdown cells. Using these cells, we then performed two-dimensional gel electrophoresis in conjunction with mass spectrometry to assess changes in protein profiles before and after 6-OHDA treatment. Several protein spots were positively or negatively altered in DJ-1-deficient cells with or without 6-OHDA. Among the altered proteins, immunoblot analysis confirmed an increase in galectin-7 and a decrease in peroxiredoxin-6 in DJ-1 knockdown cells. Moreover, transcriptional levels of putative p53 target proteins, including selenophosphate synthetase 1 and glycogen phosphorylase, were increased in the DJ-1 knockdown cells. Taken together, our data suggest that increases in pro-apoptotic proteins and decreases in anti-apoptotic proteins render DJ-1 knockdown cells more susceptible to oxidative stress.
authors.affiliation: Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea.
authors.forename: Su-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yun-Jong
authors.initials: YJ
authors.lastname: Park
authors.forename: Young J
authors.initials: YJ
authors.lastname: Oh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D019610:Cytoprotection; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D040901:Proteomics; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D016627:Oxidopamine; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1