title: DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.
abstract: Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Parsanejad
authors.affiliation: Department of Medicine and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at Univeristy of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Noam
authors.initials: N
authors.lastname: Bourquard
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dianbo
authors.initials: D
authors.lastname: Qu
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: En
authors.initials: E
authors.lastname: Huang
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Maxime W C
authors.initials: MW
authors.lastname: Rousseaux
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Hossein
authors.initials: H
authors.lastname: Aleyasin
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Ophthalmology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Isabella
authors.initials: I
authors.lastname: Irrcher
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Callaghan
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dominique C
authors.initials: DC
authors.lastname: Vaillant
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, Canada.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Kim
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Slack
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, Canada.
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Department of Medicine and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at Univeristy of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
authors.affiliation: Ottawa Institute of Systems Biology (OISB), University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada; Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Korea.
authors.forename: David S
authors.initials: DS
authors.lastname: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000096:biosynthesis* / Q000235:genetics; D002470:Cell Survival; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D000071617:Protein Deglycase DJ-1
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D043303:Aryldialkylphosphatase