Transduction of familial amyotrophic lateral sclerosis-related mutant PEP-1-SOD proteins into neuronal cells

• Published in: Molecules and cells Vol. 25; no. 1; pp. 55 - 63
• Main Authors: An, J.J. (Hallym University, Chuncheon, Republic of Korea), Lee, Y.P. (Hallym University, Chuncheon, Republic of Korea), Kim, S.Y. (Hallym University, Chuncheon, Republic of Korea), Lee, S.H. (Hallym University, Chuncheon, Republic of Korea), Kim, D.W. (Hallym University, Chuncheon, Republic of Korea), Lee, M.J. (Hallym University, Chuncheon, Republic of Korea), Jeong, M.S. (Hallym University, Chuncheon, Republic of Korea), Jang, S.H. (Hallym University, Chuncheon, Republic of Korea), Kang, J.H. (Cheongju University, Cheongju, Republic of Korea), Kwon, H.Y. (Hallym University, Chuncheon, Republic of Korea), Kang, T.C. (Hallym University, Chuncheon, Republic of Korea), Won, M.H. (Hallym University, Chuncheon, Republic of Korea), Cho, S.W. (University of Ulsan College of Medicine, Seoul, Republic of Korea), Kwon, O.S. (Kyungpook National University, Daegu, Republic of Korea), Lee, K.S. (Hallym University, Chuncheon, Republic of Korea), Park, J.S. (Hallym University, Chuncheon, Republic of Korea), Eum, W.S. (Hallym University, Chuncheon, Republic of Korea), E-mail: wseum@hallym.ac.kr, Choi, S.Y. (Hallym University, Chuncheon, Republic of Korea), E-mail: sychoi@hallym.ac.kr
• Format: Journal Article
• Language: English
• Published: United States 한국분자세포생물학회 29.02.2008
• Subjects: amyotrophic lateral sclerosis (ALS); Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Animals; Astrocytes - cytology; Astrocytes - physiology; Cell Survival; Cells, Cultured; Cu,Zn-superoxide dismutase (SOD1); Cysteamine - analogs & derivatives; Cysteamine - metabolism; HEAT SHOCK PROTEINS; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Oxidative Stress; Peptides - genetics; Peptides - metabolism; protein transduction; PROTEINAS DE SHOCK TERMICO; PROTEINE DE CHOC THERMIQUE; Rats; Rats, Wistar; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Transduction, Genetic; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1016/S1016-8478(23)17550-9

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.