title: Neuroprotective effect of Cu,Zn-superoxide dismutase fused to a TCTP-derived protein transduction domain.
abstract: Previously, we have reported that a 10-amino acid peptide (MIIYRDLISH) derived from the NH(2)-terminus of the human translationally controlled tumor protein (TCTP) functions as a protein transduction domain (PTD). In this study, we evaluated the transduction ability of SOD fused to TCTP-PTD (TCTP-SOD) into various cell lines. We also evaluated its ability to protect cells against paraquat-induced cell damage, in vitro and its neuroprotective effect in vivo against kainic acid-induced neuronal damage in an animal model. TCTP-SOD was transduced into various cell lines in a dose- and time-dependent manner without cytotoxic effect. Furthermore, TCTP-SOD showed cytoprotective activity in SH-SY5Y cells, and intraperitoneally, injected TCTP-SOD was delivered into the mouse brain and protected the cells in the hippocampal region against the damage induced by kainic acid. We propose TCTP-SOD as a potential candidate drug for treatment of brain diseases.
authors.affiliation: College of Pharmacy, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Lee
authors.forename: Sabin
authors.initials: S
authors.lastname: Kim
authors.forename: Dong Hae
authors.initials: DH
authors.lastname: Shin
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyunglim
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010269:Paraquat / Q000633:toxicity; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors; D000090324:Tumor Protein, Translationally-Controlled 1; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D054322:tat Gene Products, Human Immunodeficiency Virus; D013482:Superoxide Dismutase; D010269:Paraquat; D007608:Kainic Acid