title: DJ-1 mediates paraquat-induced dopaminergic neuronal cell death.
abstract: There are two causes of Parkinson's disease (PD): environmental insults and genetic mutations of PD-associated genes. Environmental insults and genetic mutations lead to mitochondrial dysfunction, and a combination of mitochondrial dysfunction and increased oxidative stress in dopaminergic neurons is thought to contribute to the pathogenesis of PD. Among the PD-associated genes, DJ-1 acts as a redox sensor for oxidative stress and has been also proposed to maintain mitochondrial complex I activity. To understand molecular functions of DJ-1 in the cell, we have generated DJ-1 null cells from the DJ-1(-/-) mouse embryos. Using these null cells, we investigated the susceptibility to an environmental toxin, paraquat, which is known to inhibit mitochondrial complex I. Interestingly, we found that DJ-1 null cells showed a resistance to paraquat-induced apoptosis, including reduced poly (ADP-ribose) polymerase and procaspase-3. Also DJ-1 null cells generated less superoxide than SN4741 cells by paraquat treatment. Consistent with the reduced paraquat sensitivity, DJ-1 null cells showed reduced complex I activity, which was partially rescued by ectopic DJ-I expression. In summary, our results suggest that DJ-1 is critical to maintain mitochondrial complex I and complex I could be a key target in interaction of paraquat toxicity and DJ-1 for giving rise to PD.
authors.affiliation: Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, South Korea. guswidia@cnu.ac.kr
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Heo
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Shim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Kang Sik
authors.initials: KS
authors.lastname: Seo
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Han
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.forename: Jin H
authors.initials: JH
authors.lastname: Son
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D005434:Flow Cytometry; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D010269:Paraquat / Q000633:toxicity*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054464:Peroxiredoxins; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism
chemical_list: D015513:Oncogene Proteins; D013481:Superoxides; D012313:RNA; D054464:Peroxiredoxins; D011065:Poly(ADP-ribose) Polymerases; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D053148:Caspase 3; D010269:Paraquat; D004298:Dopamine