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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Transduced Tat-α-Synuclein Protects against Oxidative Stress In vitro and In vivo

  • Choi, Hee-Soon (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Lee, Sun-Hwa (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Kim, So-Young (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • An, Jae-Jin (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Hwang, Seok-Il (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Kim, Dae-Won (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Yoo, Ki-Yeon (Department of Anatomy, College of Medicine, Hallym University) ;
  • Won, Moo-Ho (Department of Anatomy, College of Medicine, Hallym University) ;
  • Kang, Tae-Cheon (Department of Anatomy, College of Medicine, Hallym University) ;
  • Kwon, Hyung-Joo (Department of Microbiology, College of Medicine, Hallym University) ;
  • Kang, Jung-Hoon (Department of Genetic Engineering, Cheongju University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Kwon, Oh-Shin (Department of Biochemistry, Kyungpook National University) ;
  • Choi, Jin-Hi (Research Laboratory of Cell Tech. Korea) ;
  • Park, Jin-Seu (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Eum, Won-Sik (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Choi, Soo-Young (Department of Biomedical Sciences and Research Institute for Bioscience and Biotechnology, Hallym University)
  • Received : 2006.01.16
  • Accepted : 2006.01.18
  • Published : 2006.05.31
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Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although many studies showed that the aggregation of $\alpha$-synuclein might be involved in the pathogenesis of PD, its protective properties against oxidative stress remain to be elucidated. In this study, human wild type and mutant $\alpha$-synuclein genes were fused with a gene fragment encoding the nine amino acid trans activator of transcription (Tat) protein transduction domain of HIV-l in a bacterial expression vector to produce a genetic in-frame WT Tat-$\alpha$-synuclein (wild type) and mutant Tat-a-synucleins (mutants; A30P and A53T), respectively, and we investigated the protective effects of wild type and mutant Tat-$\alpha$-synucleins in vitro and in vivo. WT Tat-$\alpha$-synuclein rapidly transduced into an astrocyte cells and protected the cells against paraquat induced cell death. However, mutant Tat-$\alpha$-synucleins did not protect at all. In the mice models exposed to the herbicide paraquat, the WT Tat-$\alpha$-synuclein completely protected against dopaminergic neuronal cell death, whereas mutants failed in protecting against oxidative stress. We found that these protective effects were characterized by increasing the expression level of heat shock protein 70 (HSP70) in the neuronal cells and this expression level was dependent on the concentration of transduced WT Tat-$\alpha$-synuclein. These results suggest that transduced Tat-$\alpha$-synuclein might protect cell death from oxidative stress by increasing the expression level of HSP70 in vitro and in vivo and this may be of potential therapeutic benefit in the pathogenesis of PD.

Keywords

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