Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice
Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice
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DOI：
10.1016/j.nbd.2009.08.013
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发表时间：
2009-12-01
影响因子：
6.1
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
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作者：
Ito, Yasushi;Yamada, Mitsunori;Hara, Hideaki
内质网（ER）应激诱导的神经元死亡可能在肌萎缩侧索硬化（ALS）的发病机制中起关键作用。然而，CCAAT/增强子结合蛋白（C/EBP）同源蛋白（CHOP），ER应激凋亡介质，是否参与ALS的发病机制是有争议的。在这里，我们证明了表达水平和定位的CHOP在散发性ALS患者和ALS转基因小鼠的脊髓免疫组织化学。在散发性ALS患者的脊髓中，CHOP显著上调，但在对照组中通常以低水平表达。同样，在ALS转基因小鼠脊髓中，CHOP表达在14周（症状期）和18至20周（终末期）增加。此外，CHOP的定位在运动神经元和神经胶质细胞，如少突胶质细胞，星形胶质细胞和小胶质细胞中合并。这些结果表明，运动神经元和神经胶质细胞CHOP的上调可能在ALS的发病机制中起关键作用。(C)2009 Elsevier Inc. All rights reserved.
Endoplasmic reticulum (ER) stress-induced neuronal death may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, whether CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), an ER-stress apoptotic mediator, is involved in the pathogenesis of ALS is controversial. Here we demonstrate the expression levels and localization of CHOP in spinal cords of both sporadic ALS patients and ALS transgenic mice by immunohistochemistry. In the spinal cords of sporadic ALS patients, CHOP was markedly up-regulated but typically expressed at low levels in those of the control. Likewise, CHOP expression increased at 14 (symptomatic stage) and 18 to 20 weeks (end stage) in ALS transgenic mice spinal cords. Furthermore, localizations of CHOP were merged in motor neurons and glial cells, such as oligodendrocytes, astrocytes, and microglia. These results indicate that the up-regulation of CHOP in motor neurons and glial cells may play pivotal roles in the pathogenesis of ALS. (C) 2009 Elsevier Inc. All rights reserved.