Defective neurite outgrowth in aphidicolin/cAMP-induced motor neurons expressing mutant Cu/Zn superoxide dismutase
Defective neurite outgrowth in aphidicolin/cAMP-induced motor neurons expressing mutant Cu/Zn superoxide dismutase
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DOI：
10.1016/s0736-5748(02)00052-7
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发表时间：
2002-10-01
影响因子：
1.8
通讯作者：
Kim, M
中科院分区：
文献类型：
--
作者：
Lee, KW;Kim, HJ;Kim, M
肌萎缩侧索硬化症（ALS）是一种以运动神经元受累为特征的进行性神经退行性疾病。在某些家族性ALS病例中发现了人类Cu/Zn超氧化物歧化酶（SOD 1）基因的突变。许多研究报道了SOD 1突变相关的神经变性。然而，突变的SOD 1是否影响神经发育尚未得到证实。我们开发了运动神经元-神经母细胞瘤杂交细胞，表达突变体（G93 A）或野生型（WT）SOD 1。用双丁酰cAMP和阿非迪霉素诱导细胞分化。突变体表现出神经突生长缺陷，并降低了生存能力。细胞色素c释放和核碎裂。Western blot分析显示，神经丝和微管相关蛋白-2（MAP-2）的数量在分化过程中减少。这些结果表明，突变SOD I细胞的轴突生长缺陷是一种细胞骨架缺陷，并与神经元死亡。(C)2002年ISDN。由爱思唯尔科技有限公司出版。保留所有权利。
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 SOD I cells is a cytoskeletal defect and is associated with neuronal death. (C) 2002 ISDN. Published by Elsevier Science Ltd. All rights reserved.