Overexpression of BAT3 Alleviates Prion Protein Fragment PrP106-126-Induced Neuronal Apoptosis
Overexpression of BAT3 Alleviates Prion Protein Fragment PrP106-126-Induced Neuronal Apoptosis
复制标题
BAT3 的过表达可减轻朊病毒蛋白片段 PrP106-126 诱导的神经元凋亡
DOI：
10.1111/cns.12243
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发表时间：
2014-08-01
影响因子：
5.5
通讯作者：
Zhao, De-Ming
中科院分区：
文献类型：
--
作者：
Song, Zhi-Qi;Yang, Li-Feng;Zhao, De-Ming
背景和目的：Pron病是一组以神经元死亡和变性为特征的感染性神经退行性疾病。人类白细胞抗原B相关转录本3(BAT3)是一种重要的细胞凋亡调节因子。因此，我们研究了BAT3和Prion蛋白之间的相互作用以及BAT3在PrP106-126诱导的细胞凋亡中的潜在作用。方法：用BAT3-HA和PRNP-EGFP表达载体分别在Hela、Neuro2A和原代神经细胞中过表达BAT3和Prion蛋白，并用免疫荧光和Western blotting方法研究它们之间的关系。采用CCK-8比色法和末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)检测BAT3对PrP106-126诱导的细胞毒性和细胞凋亡的影响。用Western blotting检测细胞色素c和Bcl2的表达。结果：BAT3能与PrP蛋白相互作用，增强PrP的表达。PrP106-126多肽处理后，BAT3从胞核转运到胞浆，提高了细胞存活率，并通过稳定Bcl2蛋白水平和抑制细胞色素c释放到胞浆，保护神经元免受PrP106-126诱导的细胞凋亡。结论：PrP106-126通过过度表达BAT3对PrP106-126诱导的细胞凋亡过程进行调控是一种新的分子机制，该机制可能对体内PrP106-126诱导PrP106-126相关神经退行性疾病神经元存活的基本调控机制具有重要意义。
Backgrounds and aims: Prion diseases are a group of infectious neurodegenerative diseases characterized by neuronal death and degeneration. Human leukocyte antigen-B-associated transcript 3 (BAT3) is an important apoptosis regulator. We therefore investigated the interactions between BAT3 and prion protein and the potential role of BAT3 in PrP106-126-induced apoptosis. Methods: BAT3 and prion protein were overexpressed in Hela, Neuro2A, or primary neuronal cells by transfection with BAT3-HA or PRNP-EGFP expression plasmids and their relationship studied by immunofluorescence and Western blotting. The effect of BAT3 on PrP106-126-induced cytotoxicity and apoptosis was detected by the CCK-8 assay and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. The expression of cytochrome c and Bcl-2 was examined by Western blotting. Results: BAT3 interacted with prion protein and enhanced PrP expression. After PrP106-126 peptide treated, BAT3 was transported from the nucleus to cytoplasm, increased cell viability, and protected neurons from PrP106-126-induced apoptosis through stabilizing the level of Bcl-2 protein and inhibiting the release of cytochrome c to cytoplasm. Conclusions: Our present data showed a novel molecular mechanism of PrP106-126-induced apoptotic process regulation through the overexpression of BAT3, which may be important for the basic regulatory mechanism of neuron survival in prion diseases and associated neurodegenerative diseases in vivo.