ER stress response in NG108-15 cells involves upregulation of syntaxin 5 expression and reduced amyloid β peptide secretion
ER stress response in NG108-15 cells involves upregulation of syntaxin 5 expression and reduced amyloid β peptide secretion
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NG108-15 细胞中的 ER 应激反应涉及突触融合蛋白 5 表达的上调和淀粉样蛋白 β 肽分泌的减少
DOI：
10.1016/j.yexcr.2015.01.001
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
and Kimio Akagawa
中科院分区：
文献类型：
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作者：
Kei Suga;Ayako Saito;and Kimio Akagawa
内质网（ER）应激在阿尔茨海默病（AD）等神经退行性疾病的发病机制中起重要作用。我们以前表明，操纵ER-高尔基体可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（ER-高尔基体陷阱）syntaxin 5（Syx 5）导致高尔基体形态和AD相关蛋白的加工发生变化。为了了解这些现象的病理生理意义，我们研究了Syx 5的表达是否被ER应激改变。ER-高尔基体陷阱Syx 5和Bet 1的从头合成由各种ER应激物诱导。Syx 5和Bet 1的表达升高与这些蛋白质在囊泡组分中的水平升高相关，包括ER-高尔基体-中间室/囊泡管状簇。此外，内质网应激减少淀粉样β（Aβ）肽的分泌。在无内质网应激的条件下，Syx 5表达的敲低增强了Aβ肽的分泌。此外，由ER应激引起的Aβ肽分泌减少可通过Syx 5敲低显著逆转。这些发现表明Syx 5在β-淀粉样蛋白前体蛋白加工和凋亡细胞死亡前的ER应激反应中起重要作用，并可能参与这两种途径之间的串扰。
Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of neurodegenerative diseases such as Alzheimer׳s disease (AD). We previously showed that manipulation of the ER–Golgi-solubleN-ethylmaleimide-sensitive factor-attachment protein receptors (ER–Golgi SNARE) syntaxin 5 (Syx5) causes changes in Golgi morphology and the processing of AD-related proteins. To understand the pathophysiologic significance of these phenomena, we examined whether the expression of Syx5 is altered by ER stress. De novo synthesis of ER–Golgi SNARE Syx5 and Bet1 was induced by various ER stressors. Elevated expression of Syx5 and Bet1 was associated with increased levels of these proteins in vesicular components, including ER–Golgi-intermediate-compartment/vesicular tubular clusters. In addition, ER stress diminished amyloid β (Aβ) peptide secretion. Knockdown of Syx5 expression enhanced the secretion of Aβ peptides under condition without ER stress. Moreover, diminished Aβ peptide secretion resulting from ER stress was significantly reversed by Syx5 knockdown. These findings suggest that Syx5 plays important roles in β-amyloid precursor protein processing and in the ER stress response that precedes apoptotic cell death and may be involved in the crosstalk between these two pathways.