Increased expression and retention of the secretory chaperone proSAAS following cell stress.

Increased expression and retention of the secretory chaperone proSAAS following cell stress.
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DOI:
10.1007/s12192-020-01128-7
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发表时间:
2020-11
影响因子:
3.8
通讯作者:
Lindberg I
Lindberg I
中科院分区:
生物学3区
文献类型:
--
作者:
Shakya M;Yildirim T;Lindberg I

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神经元和内分泌细胞的分泌途径包含多种旨在对抗细胞应激的机制。这些不仅包括未折叠的蛋白质反应途径,还包括各种伴侣蛋白,它们共同作用,确保对分泌和膜结合分子的蛋白抑制控制。在这些伴侣中,研究最少的是一种神经和内分泌特异的分子,称为proSAAS。这种小分子伴侣蛋白在体外和细胞内都是一种有效的抗聚集剂,也是阿尔茨海默病的脑脊液生物标记物。在目前的研究中,我们研究了proSAAS和其他分泌伴侣一样,可能代表一种应激反应蛋白的想法。我们发现神经和内分泌细胞暴露于细胞应激源衣霉素和thapsigargin增加了Neuro2A细胞中细胞proSAAS的mRNA和蛋白。矛盾的是,ProSAAS的分泌却被这些药物抑制。将Neuro2A细胞暴露在低浓度的低氧应激诱导剂氯化钴或氧化应激源亚砷酸钠中,也会增加细胞中ProSAAS的含量并减少其分泌。我们的结论是,小分泌伴侣proSAAs的细胞水平受到细胞应激的正向调节。
The secretory pathway of neurons and endocrine cells contains a variety of mechanisms designed to combat cellular stress. These include not only the unfolded protein response pathways but also diverse chaperone proteins that collectively work to ensure proteostatic control of secreted and membrane-bound molecules. One of the least studied of these chaperones is the neural- and endocrine-specific molecule known as proSAAS. This small chaperone protein acts as a potent anti-aggregant both in vitro and in cellulo and also represents a cerebrospinal fluid biomarker in Alzheimer’s disease. In the present study, we have examined the idea that proSAAS, like other secretory chaperones, might represent a stress-responsive protein. We find that exposure of neural and endocrine cells to the cell stressors tunicamycin and thapsigargin increases cellular proSAAS mRNA and protein in Neuro2A cells. Paradoxically, proSAAS secretion is inhibited by these same drugs. Exposure of Neuro2A cells to low concentrations of the hypoxic stress inducer cobalt chloride, or to sodium arsenite, an oxidative stressor, also increases cellular proSAAS content and reduces its secretion. We conclude that the cellular levels of the small secretory chaperone proSAAS are positively modulated by cell stress.
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