DJ-1 has a role in antioxidative stress to prevent cell death.
Deletion and point (L166P) mutations of DJ-1 have recently been shown to be responsible for the onset of familial Parkinson's disease (PD, PARK7). The aim of this study was to determine the role of DJ-1 in PD. We first found that DJ-1 eliminated hydrogen peroxide in vitro by oxidizing itself. We then found that DJ-1 knockdown by short interfering RNA rendered SH-SY5Y neuroblastoma cells susceptible to hydrogen peroxide-, MPP+- or 6-hydroxydopamine-induced cell death and that cells harbouring mutant forms of DJ-1, including L166P, became susceptible to death in parallel with the loss of oxidized forms of DJ-1. These results clearly showed that DJ-1 has a role in the antioxidative stress reaction and that mutations of DJ-1 lead to cell death, which is observed in PD.
Taira
Takahiro
T
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Sapporo 060-0812, Japan.
Saito
Yoshiro
Y
Niki
Takeshi
T
Iguchi-Ariga
Sanae M M
SM
Takahashi
Kazuhiko
K
Ariga
Hiroyoshi
H
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation / Q000235:genetics; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1