Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Tat-Fused Recombinant Human SAG Prevents Dopaminergic Neurodegeneration in a MPTP-Induced Parkinson's Disease Model

  • Sohn, Eun Jeong (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) ;
  • Kim, Dae Won (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University) ;
  • Ahn, Eun Hee (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Jo, Hyo Sang (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, Duk-Soo (Department of Anatomy, College of Medicine, Soonchunhyang University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Han, Kyu Hyung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Park, Jinseu (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) ;
  • Hwang, Hyun Sook (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 : 2013.10.30
  • Accepted : 2014.01.27
  • Published : 2014.03.31
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Abstract

Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson's disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium ($MPP^+$) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity. Western blot and immunohistochemical analysis showed that, unlike SAG, Tat-SAG transduced efficiently into SH-SY5Y cells and into the brain, respectively. Tat-SAG remarkably suppressed ROS generation, DNA damage, and the progression of apoptosis, caused by $MPP^+$ in SH-SY5Y cells. Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model. Tat-SAG-treated mice showed significant enhanced motor activities, compared to SAG- or Tat-treated mice. Therefore, our results suggest that Tat-SAG has potential as a therapeutic agent against ROS-related diseases such as PD.

Keywords

References

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