Transduction of familial amyotrophic lateral sclerosis-related mutant PEP-1-SOD proteins into neuronal cells.
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.
An
Jae Jin
JJ
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
Lee
Yeom Pyo
YP
Kim
So Young
SY
Lee
Sun Hwa
SH
Kim
Dae Won
DW
Lee
Min Jung
MJ
Jeong
Min Seop
MS
Jang
Sang Ho
SH
Kang
Jung Hoon
JH
Kwon
Hyeok Yil
HY
Kang
Tae-Cheon
TC
Won
Moo Ho
MH
Cho
Sung-Woo
SW
Kwon
Oh-Shin
OS
Lee
Kil Soo
KS
Park
Jinseu
J
Eum
Won Sik
WS
Choi
Soo Young
SY
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
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