論文

国際誌
2022年1月

USP10 inhibits the dopamine-induced reactive oxygen species-dependent apoptosis of neuronal cells by stimulating the antioxidant Nrf2 activity.

The Journal of biological chemistry
  • Junya Sango
  • ,
  • Taichi Kakihana
  • ,
  • Masahiko Takahashi
  • ,
  • Yoshinori Katsuragi
  • ,
  • Sergei Anisimov
  • ,
  • Masaaki Komatsu
  • ,
  • Masahiro Fujii

298
1
開始ページ
101448
終了ページ
101448
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jbc.2021.101448

Nrf2 is an antioxidant transcriptional activator in many types of cells, and its dysfunction plays key roles in a variety of human disorders, including Parkinson's disease (PD). PD is characterized by the selective loss of dopaminergic neurons in PD-affected brain regions. Dopamine treatment of neuronal cells stimulates the production of reactive oxygen species (ROS) and increases ROS-dependent neuronal apoptosis. In this study, we found that the ubiquitin-specific protease 10 (USP10) protein reduces dopamine-induced ROS production of neuronal cells and ROS-dependent apoptosis by stimulating the antioxidant activity of Nrf2. USP10 interacted with the Nrf2 activator p62, increased the phosphorylation of p62, increased the interaction of p62 with the Nrf2 inhibitor Keap1, and stimulated Nrf2 antioxidant transcriptional activity. In addition, USP10 augmented dopamine-induced Nrf2 translation. Taken together, these results indicate that USP10 is a key regulator of Nrf2 antioxidant activity in neuronal cells and suggest that USP10 activators are promising therapeutic agents for oxidative stress-related diseases, including PD.

リンク情報
DOI
https://doi.org/10.1016/j.jbc.2021.101448
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34838592
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689211
ID情報
  • DOI : 10.1016/j.jbc.2021.101448
  • PubMed ID : 34838592
  • PubMed Central 記事ID : PMC8689211

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