title: Induction of reactive oxygen species by bisphenol A and abrogation of bisphenol A-induced cell injury by DJ-1.
abstract: DJ-1 was first identified as an activated ras-dependent oncogene. DJ-1 is related to male fertility, and its expression in sperm decreases in response to exposure to a number of reproductive toxicants. DJ-1 has been associated with the onset of familial Parkinson's disease (PD) in humans, and has been found to have activity against oxidative damage by eliminating reactive oxygen species (ROS). In this study, we investigated the role of DJ-1 in oxidative stresses by administration of bisphenol A (BPA), which has been reported to induce oxidative stress in rodents, to male mice and cultured cells. In male mice, we found that BPA significantly increased the expression level of DJ-1 in the sperm and brain. In cultured Neuro2a and GC1 cells, we found that BPA induced ROS production and significantly compromised mitochondrial function concomitant with elevated expression and oxidization of DJ-1. DJ-1 was found to maintain the complex I activity against BPA-induced oxidative stress after the localization in mitochondria. The results showed that DJ-1 plays a role in the prevention of mitochondrial injury-induced cell death.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Graduate School of Agriculture, Hokkaido University, Sapporo 060-0812, Japan. hiro@pharm.hokudai.ac.jp
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ooe
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taira
authors.forename: Sanae M M
authors.initials: SM
authors.lastname: Iguchi-Ariga
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D054464:Peroxiredoxins; D010636:Phenols / Q000633:toxicity*; D000071617:Protein Deglycase DJ-1; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D016166:Free Radical Scavengers; D015513:Oncogene Proteins; D054464:Peroxiredoxins; D010636:Phenols; D000071617:Protein Deglycase DJ-1; C503466:PARK7 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds