Transduced Human Copper Chaperone for Cu,Zn-SOD (PEP-1-CCS) Protects Against Neuronal Cell Death

  • Choi, Soo Hyun (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, Dae Won (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Kim, So Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • An, Jae Jin (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Lee, Sun Hwa (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Hee Soon (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Sohn, Eun Jung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Hwang, Seok-Il (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, 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) ;
  • 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) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
  • Received : 2005.07.15
  • Accepted : 2005.08.29
  • Published : 2005.12.31

Abstract

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

Keywords

Copper Chaperone for SOD (CCS);Cu,Zn-SOD;Ischemia;PEP-1 Peptide;Protein Transduction

Acknowledgement

Supported by : Korean Science and Engineering Foundation

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