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Am J Physiol Cell Physiol 288: C253-C259, 2005. First published September 29, 2004; doi:10.1152/ajpcell.00014.2004
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NERVOUS SYSTEM CELL BIOLOGY

Overexpression of mutated Cu,Zn-SOD in neuroblastoma cells results in cytoskeletal change

Rina Takamiya,1 Motoko Takahashi,1 Yong Seek Park,1 Yoshie Tawara,1 Noriko Fujiwara,2 Yasuhide Miyamoto,1 Jianguo Gu,1 Keiichiro Suzuki,2 and Naoyuki Taniguchi1

1Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan; and 2Department of Biochemistry, Hyogo College of Medicine, Hyogo, Japan

Submitted 9 January 2004 ; accepted in final form 21 September 2004

Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons in the spinal cord and the motor cortex. It has been shown that 15–20% of patients with familial ALS (FALS) have defects in the Sod1 gene, which encodes Cu,Zn-superoxide dismutase (SOD). To elucidate the pathological role of mutated Cu,Zn-SOD, we examined the issue of whether mutated Cu,Zn-SOD affects the cell cycle. Mouse neuroblastoma Neuro-2a cells were transfected with human wild-type or mutated (G37R, G93A) Cu,Zn-SOD. Mutated, Cu,Zn-SOD-transfected cells exhibited marked retardation in cell growth and G2/M arrest. They also displayed lower reactivity to phalloidin, indicating that the cytoskeleton was disrupted. Immunoprecipitation, two-dimensional gel electrophoresis, and Western blot analysis indicated that mutated Cu,Zn-SOD associates with actin. Similar results were obtained by in vitro incubation experiments with purified actin and mutated Cu,Zn-SOD (G93A). These results suggest that mutated Cu,Zn-SOD in FALS causes cytoskeletal changes by associating with actin, which subsequently causes G2/M arrest and growth retardation.

amyotrophic lateral sclerosis; copper; zinc superoxide dismutase; G2/M arrest; neurodegenerative disease


Address for reprint requests and other correspondence: N. Taniguchi, Dept. of Biochemistry, Osaka Univ. Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan (E-mail: proftani{at}biochem.med.osaka-u.ac.jp)






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