SMN protects cells against mutant SOD1 toxicity by increasing chaperone activity.
SMN protects cells against mutant SOD1 toxicity by increasing chaperone activity.
复制标题
SMN 通过增加伴侣活性来保护细胞免受突变型 SOD1 毒性。
DOI：
10.1016/j.bbrc.2007.10.096
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发表时间：
2007
影响因子：
3.1
通讯作者：
Zhou,Jianhua
中科院分区：
文献类型：
--
作者：
Zou,Tie;Ilangovan,Raju;Yu,Furong;Xu,Zuoshang;Zhou,Jianhua
运动神经元存活基因（SMN 1）的缺失或突变导致脊髓性肌萎缩症（SMA），这是一种运动神经元退行性疾病。为了研究SMN的功能，我们用SMN和突变型超氧化物歧化酶1（SOD 1）构建体共转染小鼠NSC 34细胞。我们证明了SMN保护NSC 34细胞免受氧化应激下突变SOD 1诱导的细胞死亡。进一步的研究表明，野生型SMN的过表达上调了伴侣蛋白活性。相反，伴侣活性在表达SMN突变体Y272 C的细胞中或在SMN被shRNA抑制的细胞中降低。使用表达GST-SMN或纯化的GST-SMN蛋白的细菌裂解物的体外测定显示，GST-SMN减少过氧化氢酶聚集，表明SMN可能具有伴侣活性。我们的结论是，SMN起着保护作用，在运动神经元的伴侣活性。我们的研究结果为SMA和肌萎缩侧索硬化症（ALS）治疗的潜在发展提供了支持。
Deletion or mutation of the survival of motor neuron (SMN1) gene causes Spinal Muscular Atrophy (SMA), a motor neuron degenerative disease. To study the SMN function, we co-transfected mouse NSC34 cells with SMN and mutant superoxide dismutase 1 (SOD1) constructs. We demonstrated that SMN protected NSC34 cells against cell death induced by mutant SOD1 under oxidative stress. Further studies indicated that over-expression of wild-type SMN up-regulated chaperone activity. In contrast, chaperone activity was decreased in cells expressing SMN mutant Y272C or in cells with SMN suppressed by shRNA. In vitro assays using bacteria lysates expressing GST-SMN or purified GST-SMN protein showed that the GST-SMN reduced catalase aggregation, indicating that SMN may possess chaperone activity. We conclude that SMN plays a protective role in motor neurons by its chaperone activity. Our results provide support for the potential development of therapy for SMA and amyotrophic lateral sclerosis (ALS).