DJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress

作者：Parsanejad Mohammad; Bourquard Noam; Qu Dianbo; Zhang Yi; Huang En; Rousseaux Maxime W C; Aleyasin Hossein; Irrcher Isabella; Callaghan Steve; Vaillant Dominique C; Kim Raymond H; Slack Ruth S; Mak Tak W; Reddy Srinivasa T; Figeys Daniel; Park David S^*

来源：PLos One, 2014, 9(9): e106601.

DOI：10.1371/journal.pone.0106601

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson%26apos;s disease (PD). While its physiological 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.

• 出版日期2014-9-11