Wang Li, Zheng Yansong, Gao Xiaoxiao, Liu Yingchun, You Xiaoqing
Department of Cell Biology and Genetics/Center for Cell and Developmental Biology, School of Basic Medical Sciences, Fujian Medical University Fuzhou 350122, Fujian, China.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Fujian Medical University 350005 Fujian, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10770-10780. eCollection 2017.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder disease in elderly. It is characterized by the formation of amyloid plaques and nerve cells apoptosis in the brain. This study focuses on the association between nerve cells apoptosis and nuclear receptors within AD. Thus, we detected the changes of the expression and subcellular localization of RXRα/Nur77 and the apoptotic rate of neuroblastoma cells, SH-SY5Y cells and nerve cells in C57BL/6 mouse hippocampus in Alzheimer's disease pathologic condition, and investigated the effect of RXRα exporting inhibition caused by 9-cis-RA on the apoptosis of neurons. We demonstrated that Aβ peptide and HO treatment could result in the translocation of RXRα and Nur77 from the nucleus to the mitochondria, and the ligand of RXR, 9-cis-RA, treatment can block the above phenomenon. More importantly, 9-cis-RA treatment could reduce the apoptotic rate of neurons caused by HO or Aβ stimulation via enhancing the expression level of Bcl-2 protein. Therefore, our studies revealed a critical role of RXRα/Nur77 in 9-cis-RA-mediated anti-apoptosis in nerve cells and provided novel information for better management of AD.
阿尔茨海默病（AD）是老年人中最常见的神经退行性疾病。其特征是大脑中形成淀粉样斑块和神经细胞凋亡。本研究聚焦于AD中神经细胞凋亡与核受体之间的关联。因此，我们检测了阿尔茨海默病病理状态下，神经母细胞瘤细胞、SH-SY5Y细胞以及C57BL/6小鼠海马体中神经细胞的RXRα/Nur77表达及亚细胞定位变化和凋亡率，并研究了9-顺式视黄酸（9-cis-RA）引起的RXRα输出抑制对神经元凋亡的影响。我们证明，Aβ肽和HO处理可导致RXRα和Nur77从细胞核转位至线粒体，而RXR的配体9-顺式视黄酸处理可阻断上述现象。更重要的是，9-顺式视黄酸处理可通过提高Bcl-2蛋白表达水平，降低HO或Aβ刺激引起的神经元凋亡率。因此，我们的研究揭示了RXRα/Nur77在9-顺式视黄酸介导的神经细胞抗凋亡中的关键作用，并为更好地治疗AD提供了新信息。
