title: Transduction of familial amyotrophic lateral sclerosis-related mutant PEP-1-SOD proteins into neuronal cells.
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.
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: An
authors.forename: Yeom Pyo
authors.initials: YP
authors.lastname: Lee
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Min Seop
authors.initials: MS
authors.lastname: Jeong
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Jang
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
authors.forename: Hyeok Yil
authors.initials: HY
authors.lastname: Kwon
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Moo Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Oh-Shin
authors.initials: OS
authors.lastname: Kwon
authors.forename: Kil Soo
authors.initials: KS
authors.lastname: Lee
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: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014161:Transduction, Genetic
chemical_list: D006360:Heat-Shock Proteins; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; C000606290:SOD1 protein, human; D003543:Cysteamine; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1