Proteomic analysis reveals a protective role for DJ-1 during 6-hydroxydopamine-induced cell death

Su Jeong Kim, Yun Jong Park, Young Jun Oh

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Loss-of-function mutations in the DJ-1/PARK7 gene are responsible for early-onset autosomal-recessive Parkinson's disease. DJ-1 is implicated in the protection of neurons from oxidative stress by scavenging hydrogen peroxide and regulating the transcriptional activity of multiple pathways. Here, we attempted to identify the protein profiles modulated by DJ-1 in MN9D dopaminergic neurons following 6-hydroxydopamine (6-OHDA) treatment. We found that reactive oxygen species (ROS) levels increased in DJ-1-deficient cells that were either untreated or subjected to 6-OHDA treatment. The incidence of apoptosis after 6-OHDA treatment was increased in DJ-1 knockdown cells. Using these cells, we then performed two-dimensional gel electrophoresis in conjunction with mass spectrometry to assess changes in protein profiles before and after 6-OHDA treatment. Several protein spots were positively or negatively altered in DJ-1-deficient cells with or without 6-OHDA. Among the altered proteins, immunoblot analysis confirmed an increase in galectin-7 and a decrease in peroxiredoxin-6 in DJ-1 knockdown cells. Moreover, transcriptional levels of putative p53 target proteins, including selenophosphate synthetase 1 and glycogen phosphorylase, were increased in the DJ-1 knockdown cells. Taken together, our data suggest that increases in pro-apoptotic proteins and decreases in anti-apoptotic proteins render DJ-1 knockdown cells more susceptible to oxidative stress.

Original languageEnglish
Pages (from-to)8-14
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume422
Issue number1
DOIs
Publication statusPublished - 2012 May 25

Fingerprint

Oxidopamine
Cell death
Proteomics
Cell Death
Apoptosis Regulatory Proteins
Oxidative stress
Proteins
Neurons
Peroxiredoxin VI
Oxidative Stress
Galectins
Glycogen Phosphorylase
Scavenging
Electrophoresis
Dopaminergic Neurons
Electrophoresis, Gel, Two-Dimensional
Parkinsonian Disorders
Hydrogen Peroxide
Mass spectrometry
Reactive Oxygen Species

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Proteomic analysis reveals a protective role for DJ-1 during 6-hydroxydopamine-induced cell death",
abstract = "Loss-of-function mutations in the DJ-1/PARK7 gene are responsible for early-onset autosomal-recessive Parkinson's disease. DJ-1 is implicated in the protection of neurons from oxidative stress by scavenging hydrogen peroxide and regulating the transcriptional activity of multiple pathways. Here, we attempted to identify the protein profiles modulated by DJ-1 in MN9D dopaminergic neurons following 6-hydroxydopamine (6-OHDA) treatment. We found that reactive oxygen species (ROS) levels increased in DJ-1-deficient cells that were either untreated or subjected to 6-OHDA treatment. The incidence of apoptosis after 6-OHDA treatment was increased in DJ-1 knockdown cells. Using these cells, we then performed two-dimensional gel electrophoresis in conjunction with mass spectrometry to assess changes in protein profiles before and after 6-OHDA treatment. Several protein spots were positively or negatively altered in DJ-1-deficient cells with or without 6-OHDA. Among the altered proteins, immunoblot analysis confirmed an increase in galectin-7 and a decrease in peroxiredoxin-6 in DJ-1 knockdown cells. Moreover, transcriptional levels of putative p53 target proteins, including selenophosphate synthetase 1 and glycogen phosphorylase, were increased in the DJ-1 knockdown cells. Taken together, our data suggest that increases in pro-apoptotic proteins and decreases in anti-apoptotic proteins render DJ-1 knockdown cells more susceptible to oxidative stress.",
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Proteomic analysis reveals a protective role for DJ-1 during 6-hydroxydopamine-induced cell death. / Kim, Su Jeong; Park, Yun Jong; Oh, Young Jun.

In: Biochemical and Biophysical Research Communications, Vol. 422, No. 1, 25.05.2012, p. 8-14.

Research output: Contribution to journalArticle

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