Open AccessDJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress
Author(s) -
Mohammad Parsanejad,
Noam Bourquard,
Dianbo Qu,
Yi Zhang,
Emma Huang,
Maxime W.C. Rousseaux,
Hossein Aleyasin,
Isabella Irrcher,
Steve Callaghan,
Dominique C. Vaillant,
Raymond H. Kim,
Ruth S. Slack,
Tak W. Mak,
Srinivasa T. Reddy,
Daniel Figeys,
David Park
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0106601
Subject(s) - oxidative stress , antioxidant , microbiology and biotechnology , oxidative phosphorylation , paraoxonase , in vivo , biology , chemistry , biochemistry , genetics
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.