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首页> 外文期刊>Nucleic acids research >Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP: evidence for systemic, transient ER stress during endotoxemia
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Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP: evidence for systemic, transient ER stress during endotoxemia

机译：ES-TRAP在体内外实时检测和持续监测ER应激：内毒素血症期间系统性，短暂性ER应激的证据

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Activity of secreted alkaline phosphatase (SEAP) produced by transfected cells is rapidly down-regulated by endoplasmic reticulum (ER) stress independent of transcriptional regulation. This phenomenon was observed in a wide range of cell types triggered by various ER stress inducers. The magnitude of the decrease in SEAP was proportional to the extent of ER stress and inversely correlated with the induction of endogenous ER stress markers grp78 and grp94. In contrast to SEAP, activity of secreted luciferase was less susceptible to ER stress. The decrease in SEAP activity by ER stress was caused by abnormal post-translational modification, accelerated degradation and reduced secretion of SEAP protein. In transgenic mice constitutively producing SEAP, systemic induction of ER stress led to reduction in serum SEAP. In these mice, administration with lipopolysaccharide caused rapid, transient decrease in serum SEAP activity, and it was correlated with up-regulation of grp78 in several organs including the spleen, lung, kidney, liver and heart. These results elucidated for the first time a possible involvement of transient, systemic ER stress in endotoxemia and provided evidence for usefulness of ER stress responsive alkaline phosphatase for real-time monitoring of ER stress in vitro and in vivo.
机译：转染细胞产生的分泌性碱性磷酸酶（SEAP）的活性受内质网（ER）应力快速下调，而与转录调控无关。在由各种内质网应激诱导物触发的多种细胞类型中均观察到了这种现象。 SEAP降低的幅度与ER应激的程度成正比，并且与内源性ER应激标志物grp78和grp94的诱导成反比。与SEAP相比，分泌的萤光素酶的活性对ER胁迫较不敏感。内质网应激引起的SEAP活性降低是由于异常的翻译后修饰，加速的降解和SEAP蛋白的分泌减少所致。在组成型产生SEAP的转基因小鼠中，ER应激的系统性诱导导致血清SEAP降低。在这些小鼠中，给予脂多糖会导致血清SEAP活性迅速而短暂地下降，并且与脾，肺，肾，肝和心脏等多个器官中grp78的上调相关。这些结果首次阐明了短暂的系统性ER应激可能与内毒素血症有关，并为ER应激反应性碱性磷酸酶在体外和体内实时监测ER应激中的有效性提供了证据。

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