Xie Juhua, Han Fang, Shi Yuxiu
Laboratory of Post-Traumatic Stress Disorder, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, 92 North 2nd Road, Shenyang, 110001, Liaoning Province, People's Republic of China.
Mol Cell Biochem. 2015 Jan;399(1-2):209-16. doi: 10.1007/s11010-014-2247-4. Epub 2014 Oct 14.
In our previous studies, we have found that endoplasmic reticulum (ER) stress is associated with post-traumatic stress disorder (PTSD), however, the activation of ER stress sensors in PTSD remains unclear. ATF6 alpha (ATF6α) is an ER-membrane-bound transcription factor and functions as a critical sensor and regulator of ER stress in mammalian cells. The goal of this study is to detect whether there is activation of the transcription factor ATF6α branch of the unfolded protein response in the dorsal raphe nucleus neurons of the rats exposed to single-prolonged stress (SPS), which is a model employed extensively in PTSD study. Our results have demonstrated that SPS activated the ER transmembrane protein ATF6α via its cleavage; and induced the up-regulation of the downstream targets of ATF6α, the mRNA of XBP1 and GRP94. To the best of our knowledge, this is the first study to investigate the relationship between the ATF6α pathways and PTSD, and our results show that SPS activates the ATF6α branch of the ER stress response, which may be contributed to the pathogenesis of PTSD.
在我们之前的研究中，我们发现内质网（ER）应激与创伤后应激障碍（PTSD）有关，然而，PTSD中内质网应激传感器的激活情况仍不清楚。活化转录因子6α（ATF6α）是一种内质网结合转录因子，在哺乳动物细胞中作为内质网应激的关键传感器和调节因子发挥作用。本研究的目的是检测在遭受单次长时间应激（SPS）的大鼠中缝背核神经元中，未折叠蛋白反应的转录因子ATF6α分支是否被激活，SPS是PTSD研究中广泛使用的一种模型。我们的结果表明，SPS通过切割激活内质网跨膜蛋白ATF6α；并诱导ATF6α下游靶点、XBP1和GRP94的mRNA上调。据我们所知，这是第一项研究ATF6α通路与PTSD之间关系的研究，我们的结果表明，SPS激活了内质网应激反应的ATF6α分支，这可能与PTSD的发病机制有关。
