Transduction of Familial Amyotrophic Lateral Sclerosis-related Mutant PEP-1-SOD Proteins into Neuronal Cells

  • An, Jae Jin (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Lee, Yeom Pyo (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Kim, So Young (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Lee, Sun Hwa (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Kim, Dae Won (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Lee, Min Jung (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Jeong, Min Seop (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Jang, Sang Ho (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Kang, Jung Hoon (Department of Genetic Engineering, Cheongju University) ;
  • Kwon, Hyeok Yil (Department of Physiology, College of Medicine, Hallym University) ;
  • Kang, Tae-Cheon (Department of Anatomy and Neurobiology, College of Medicine, Hallym University) ;
  • Won, Moo Ho (Department of Anatomy and Neurobiology, College of Medicine, Hallym 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) ;
  • Lee, Kil Soo (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Park, Jinseu (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Eum, Won Sik (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University)
  • Received : 2007.05.08
  • Accepted : 2007.10.05
  • Published : 2008.02.29

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective death of motor neurons. Mutations in the SOD1 gene are responsible for a familial form of ALS (FALS). Although many studies suggest that mutant SOD1 proteins are cytotoxic, the mechanism is not fully understood. To investigate the role of mutant SOD1 in FALS, human SOD1 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD fusion proteins (wild type and mutants). The expressed and purified PEP-1-SOD fusion proteins were efficiently transduced into neuronal cells. Neurones harboring the A4V, G93A, G85R, and D90A mutants of PEP-1-SOD were more vulnerable to oxidative stress induced by paraquat than those harboring wild-type proteins. Moreover, neurones harboring the mutant SOD proteins had lower heat shock protein (Hsp) expression levels than those harboring wild-type SOD. The effects of the transduced SOD1 fusion proteins may provide an explanation for the association of SOD1 with FALS, and Hsps could be candidate agents for the treatment of ALS.

Keywords

Amyotrophic Lateral Sclerosis (ALS);Cu,Zn-superoxide dismutase (SOD1);Heat shock protein (Hsp);Protein Transduction

Acknowledgement

Supported by : Korean Science and Engineering Foundation

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