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Elucidation of brefeldin A-induced ER and Golgi stress responses in Neuro2a cells.
Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2021-06-15 , DOI: 10.1007/s11010-021-04187-1
Kentaro Oh-Hashi 1, 2, 3 , Tomoyuki Hasegawa 2 , Yuri Mizutani 3 , Kanto Takahashi 2 , Yoko Hirata 1, 2, 3
Affiliation  

Brefeldin A (BFA) disrupts the structure of the Golgi apparatus to trigger ER stress signaling pathways. On the other hand, treatment with BFA induces the activation of CREB3, the protein structure of which is similar to that of ATF6. In this study, we established Neuro2a cells in which three different transcription factors, namely, ATF4, ATF3 and CREB3, were deficient using the CRISPR/Cas9 approach, and we investigated the BFA-induced ER and Golgi stress response in these cells. BFA treatment rapidly induced ATF4, ATF3, Herp and GADD153 protein expression in Neuro2a cells. ATF4-deficient Neuro2a cells exhibited significantly decreased mRNA and protein expression of ATF3 and Herp but not GADD153; however, cells deficient in ATF3 exhibited minimal effects on GADD34, GADD153 and Herp expression. The cleavage of CREB3 in Neuro2a cells was triggered by BFA; however, the expression of several ER and Golgi stress-related factors was hardly influenced by the CREB3 deficiency in these Neuro2a cells. This study shows that CREB3 minimally associates with typical ER stress-inducible responses in Neuro2a cells. Therefore, identification and characterization of the downstream transcriptional targets of CREB3 is required to clarify not only Golgi stress response but also its relationship with ER stress signaling pathways.

中文翻译:

在 Neuro2a 细胞中阐明 brefeldin A 诱导的 ER 和高尔基体应激反应。

Brefeldin A (BFA) 破坏高尔基体的结构以触发内质网应激信号通路。另一方面,用 BFA 处理会诱导 CREB3 的激活,其蛋白质结构与 ATF6 相似。在这项研究中,我们使用 CRISPR/Cas9 方法建立了其中三种不同的转录因子,即 ATF4、ATF3 和 CREB3 缺陷的 Neuro2a 细胞,我们研究了这些细胞中 BFA 诱导的 ER 和高尔基体应激反应。BFA 处理迅速诱导 Neuro2a 细胞中的 ATF4、ATF3、Herp 和 GADD153 蛋白表达。ATF4 缺陷的 Neuro2a 细胞表现出 ATF3 和 Herp 的 mRNA 和蛋白质表达显着降低,但 GADD153 没有;然而,缺乏 ATF3 的细胞对 GADD34、GADD153 和 Herp 表达的影响很小。Neuro2a 细胞中 CREB3 的裂解是由 BFA 触发的;然而,几种 ER 和高尔基体应激相关因子的表达几乎不受这些 Neuro2a 细胞中 CREB3 缺陷的影响。这项研究表明,CREB3 与 Neuro2a 细胞中典型的内质网应激诱导反应的相关性最低。因此,CREB3 下游转录靶点的鉴定和表征不仅需要阐明高尔基体应激反应,还需要阐明其与内质网应激信号通路的关系。
更新日期:2021-06-15
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