title: Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.
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.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Choi
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: An
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Hee Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Seok-Il
authors.initials: SI
authors.lastname: Hwang
authors.forename: Moo Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D003300:Copper / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018832:Molecular Chaperones / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010269:Paraquat / Q000633:toxicity; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use; D014162:Transfection
chemical_list: C114678:CCS protein, human; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D003300:Copper; D010269:Paraquat