Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron involvement. Mutations in the human Cu/Zn superoxide dismutase (SOD1) gene are found in some cases of familial ALS. Many studies have reported SOD1 mutation-related neurodegeneration. However, whether or not a mutant SOD1 affects neural development has not been demonstrated. We developed motor neuron-neuroblastoma hybrid cells that expressed a mutant (G93A) or the wild type (WT) SOD1. Cells were differentiated by dibutyryl cAMP and aphidicolin. The mutant showed a defect in neurite outgrowth and had decreased viability. Cytochrome c released and nuclear fragmentation were observed. Western blot analysis showed that the amount of neurofilament and microtubule associated proteins-2 (MAP-2) decreased during differentiation. These results suggest that the defect in neurite outgrowth of mutant SOD1 cells is a cytoskeletal defect and is associated with neuronal death.
MeSH terms
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Amyotrophic Lateral Sclerosis / enzymology*
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Amyotrophic Lateral Sclerosis / genetics
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Animals
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Aphidicolin
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cell Survival / drug effects
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Cell Survival / genetics*
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Cyclic AMP
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Cytochrome c Group / drug effects
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Cytochrome c Group / metabolism
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DNA Fragmentation / drug effects
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DNA Fragmentation / genetics
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Enzyme Inhibitors
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Humans
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Microtubule-Associated Proteins / drug effects
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Microtubule-Associated Proteins / metabolism
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Motor Neurons / drug effects
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Motor Neurons / enzymology*
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Motor Neurons / pathology
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Mutation / genetics*
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Neurites / drug effects
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Neurites / enzymology*
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Neurites / pathology
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Neurofilament Proteins / drug effects
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Neurofilament Proteins / metabolism
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Superoxide Dismutase / deficiency*
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Superoxide Dismutase / genetics
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Tumor Cells, Cultured
Substances
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Cytochrome c Group
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Enzyme Inhibitors
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Microtubule-Associated Proteins
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Neurofilament Proteins
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Aphidicolin
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Cyclic AMP
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Superoxide Dismutase