J Korean Neurol Assoc.
2002 May;20(3):273-278.
Effect of Familial Amyotrophic Lateral Sclerosis-associated Cu, Zn-superox-ide Dismutase Mutation on Neural Differentiation in Motor Neuronal Cells
- Affiliations
-
- 1Department of Neurology, Inje University Seoul Paik Hospital, Korea.
- 2Department of Neurology, Seoul Municipal Boramae Hospital, Korea.
- 3Department of Neurology, College of Medicine, Seoul National University, Korea. kwoo@plaza.snu.ac.kr
- 4Department of Biochemistry, College of Medicine, Seoul National University, Korea.
- 5Department of Pharmacology, College of Medicine, Seoul National University, Korea.
- 6Department of Anatomy, College of Medicine, Seoul National University, Korea.
- 7Department of Pathology, College of Medicine, Korea University, Korea.
Abstract
-
BACKGROUND: Mutations in the human Cu, Zn-superoxide dismutase(SOD1) gene have been identified in some cases of familial amyotrophic lateral sclerosis(ALS). The aim of this study is to delineate the effect of the SOD1 mutation on neural differentiation, and to investigate the mechanism of neuronal death.
METHODS
We studied motorneuron-neurob-lastoma hybrid cells(VSC 4.1) expressing wild type or mutant SOD1(G93A, A4V) during differentiation by dibutyryl cAMP and aphidicolin.
RESULTS
Mutant cells(G93A) revealed a decreased viability compared with the control cells, mainly in the early stage ofdifferentiation. The release of cytochrome c and increased nuclear fragmentation were observed. However, cell death was not protected by nonselective caspase inhibitor(z-VAD-fmk), but by the antioxi-dant( Trolox).
CONCLUSIONS
The results suggest that oxidative stress may be the main mechanism of neuronal death, particularly in the early stage of differentiation.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Impairment of Neurite Formation in Familial ALS-associated Cu, Zn-Superoxide Dismutase Mutant Cells
- Extracellular Toxicity of Motor Neuronal Cells Expressing Mutant Cu/Zn Superoxide Dismutase in Familial ALS Cell Line Model
- The Effect of Calcium Modulators on Motoneuron Cells Which Express Mutated Cu / Zn Superoxide Dismutase
- Anticipation and Phenotypic Heterogeneity in Korean Familial Amyotrophic Lateral Sclerosis with Superoxide Dismutase 1 Gene Mutation
- Calcium-influx increases SOD1 aggregates via nitric oxide in cultured motor neurons
