ER stress is the initial response to polyglutamine toxicity in PC12 cells.
ER stress is the initial response to polyglutamine toxicity in PC12 cells.
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DOI：
10.1016/j.bbrc.2008.10.006
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发表时间：
2008-12
影响因子：
3.1
通讯作者：
H. Nakayama;M. Hamada;N. Fujikake;Y. Nagai;Jing Zhao-;O. Hatano;K. Shimoke;M. Isosaki;M. Yoshizumi;T. Ikeuchi
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文献类型：
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作者：
H. Nakayama;M. Hamada;N. Fujikake;Y. Nagai;Jing Zhao-;O. Hatano;K. Shimoke;M. Isosaki;M. Yoshizumi;T. Ikeuchi
持续内质网（ER）应激和泛素-蛋白酶体系统（UPS）损伤可导致神经元细胞死亡。然而，这两种现象之间的关系仍然存在争议。在我们目前的研究中，我们利用扩展的聚谷氨酰胺融合蛋白（polyQ81）表达系统在PC12细胞中进一步研究内质网应激和UPS损伤在细胞死亡中的作用。表达polyq81诱导内质网应激和细胞死亡。PolyQ81还诱导了c-Jun n -末端激酶（JNK）和caspase-3的激活以及多聚素免疫反应性的增加，提示UPS损伤。内质网应激是在多泛素化蛋白积累之前诱导的。低剂量lactacystin对正常细胞和表达polyq81的细胞的细胞活力以及JNK和caspase-3的激活的影响几乎相似。这些结果表明，在这些毒性作用的初始阶段，内质网应激在UPS损伤之前介导了多谷氨酰胺毒性。
Persistent endoplasmic reticulum (ER) stress and impairment of the ubiquitin–proteasome system (UPS) cause neuronal cell death. However, the relationship between these two phenomena remains controversial. In our current study, we have utilized an expanded polyglutamine fusion protein (polyQ81) expression system in PC12 cells to further examine the involvement of ER stress and UPS impairment in cell death. The expression of polyQ81-induced ER stress and cell death. PolyQ81 also induced the activation of c-Jun N-terminal kinase (JNK) and caspase-3 and an increase in polyubiquitin immunoreactivity, suggesting UPS impairment. ER stress was induced prior to the accumulation of polyubiquitinated proteins. Low doses of lactacystin had almost similar effects on cell viability and on the activation of JNK and caspase-3 between normal cells and polyQ81-expressing cells. These results suggest that ER stress mediates polyglutamine toxicity prior to UPS impairment during the initial stages of these toxic effects.