Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

  • Yeo, Eun Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Eum, Won Sik (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Yeo, Hyeon Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Yeon Joo (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Sohn, Eun Jeong (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kwon, Hyun Jung (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University) ;
  • Kim, Dae Won (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University) ;
  • Kim, Duk-Soo (Department of Anatomy and BK21 Plus Center, College of Medicine, Soonchunhyang University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Park, Jinseu (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Han, Kyu Hyung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Lee, Keun Wook (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Park, Jong Kook (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Shin, Min Jea (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
  • Received : 2020.09.03
  • Accepted : 2020.12.10
  • Published : 2021.05.01
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Abstract

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Keywords

References

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