Nuclear translocation of DJ-1 during oxidative stress-induced neuronal cell death

Su Jeong Kim, Yun Jong Park, Ih Yeon Hwang, Moussa B.H. Youdim, Kang Sik Park, Young J. Oh

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Loss-of-function mutations in the PARK7/DJ-1 gene cause early onset autosomal-recessive Parkinson disease. DJ-1 has been implicated in protection of neurons from oxidative stress and in regulation of transcriptional activity. However, whether there is a relationship between the subcellular localization of DJ-1 and its function remains unknown. Therefore, we examined the subcellular localization of DJ-1 during dopaminergic neurodegeneration induced by various insults. Immunoblotting and immunocytochemistry showed that the nuclear pool of DJ-1 dramatically increased in both MN9D dopaminergic neuronal cells and primary cultures of mesencephalic dopaminergic neurons after 6-hydroxydopamine (6-OHDA) treatment. This was paralleled by a corresponding decrease in its cytosolic level, indicating drug-induced nuclear translocation of DJ-1. The same phenomenon was detected in other cell death paradigms induced by pro-oxidants including hydrogen peroxide and cupric chloride. Consequently, cotreatment with the antioxidant N-acetyl-l-cysteine blocked the translocation of DJ-1 into the nucleus. However, mutation at cysteine 106 had no effect on the translocation of DJ-1 into the nucleus, suggesting that reactive oxygen species-mediated downstream signaling and/or modifications other than oxidative modification are involved in its nuclear translocation. Ectopic expression of nucleus localization signal (NLS)-tagged DJ-1 prevented cell death from 6-OHDA. We investigated whether nuclear DJ-1 was involved in transcriptional regulation and found that DJ-1 was localized in promyelocytic leukemia bodies, and this localization increased upon 6-OHDA treatment. We also confirmed that binding of DJ-1 and promyelocytic leukemia bodies indeed increased after 6-OHDA treatment. Consequently, expression levels of acetylated p53 and PUMA were downregulated in cells overexpressing DJ-1 or NLS-tagged DJ-1. Taken together, our data suggest that nuclear translocation of DJ-1 may protect neurons from cell death after oxidative stress.

Original languageEnglish
Pages (from-to)936-950
Number of pages15
JournalFree Radical Biology and Medicine
Issue number4
Publication statusPublished - 2012 Aug 15

Bibliographical note

Funding Information:
This work was supported by grants from the Ministry of Science and Technology through BRC, KOSEF (SRC, R11-2008-036), Mid-Career Research Program, and WCU (R33-10014 to Y.J.O.). We thank Dr. H. Ariga for providing the human anti-C106-oxidized DJ-1 antibody.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)


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