PrP106-126诱导的小鼠成神经瘤N2a细胞NF-κB激活及神经毒性研究  

NF-κB Activated in PrP106-126-induced Neurotoxicity in Mouse Neuroblastoma Cells N2a

作　　者：白瑜[1] 周向梅[1] 尹晓敏[1] 杨建民[1] 赵德明[1] 

机构地区：[1]中国农业大学动物医学院国家动物海绵状脑病实验室,北京100193

出　　处：《畜牧兽医学报》2009年第4期544-547,共4页ACTA VETERINARIA ET ZOOTECHNICA SINICA

基　　金：国家科技支撑计划项目资助(2006BAD06A14);科技部项目资助(2005KDA21205-7;2006EA125015)

摘　　要：PrP106-126诱导的神经毒性机制仍不清楚。作者以小鼠成神经瘤细胞N2a为细胞模型,应用WesternBlot方法首次发现PrP106-126导致核转录因子NF-κB的亚单位p65蛋白转移到细胞核内,激活了NF-κB细胞信号分子。转核抑制剂NF-κB SN50预处理细胞减弱了PrP106-126诱导的NF-κB激活程度;并且DNA Ladder凋亡检测及Annexin V-FITC和PI双染流式细胞凋亡检测发现,NF-κB SN50能够抑制p65蛋白转核,在一定程度上也抑制了PrP106-126对N2a细胞的神经毒性效果。结果表明NF-κB信号分子参与了PrP106-126的神经毒性,且NF-κB信号分子的激活对N2a细胞具有促凋亡作用。PrP106-126激活N2a细胞NF-κB信号分子以及NF-κB促凋亡功能的体外研究对于阐明朊病毒病致病机理具有重要意义。The neurotoxic mechanism of PrP106-126 still remains uncertain.Herein PrP106-126-induced neurotoxicity in mouse neuroblastoma cell line N2a,for the first time we found that PrP106-126 induced p65 subunit of nuclear transcription factor NF-κB translocated into the nucleus by Western Blot assay and activated NF-κB signaling pathway.Pretreatment with nuclear translocation inhibitor NF-κB SN50 attenuated PrP106-126-induced NF-κB activity,using apoptotic DNA Ladder assay and flow cytometry（FCM） assay with Annexin V-FITC/PI double-staining,we also found that attenuated NF-κB activity was accompanied by reduced apoptotic effect by PrP106-126.The results showed that NF-κB signaling pathway was involved in PrP106-126-induced neurotoxicity,and NF-κB activation showed pro-apoptotic effect in N2a cells.The in vitro study on PrP106-126-activated NF-κB signaling pathway and its pro-apoptotic effect on N2a cells were significantly important to elucidate the neurotoxic mechanism of prion.

关 键 词：朊病毒 PrP106-126 NF-ΚB 神经毒性 小鼠成神经瘤细胞N2a 

分 类 号：S852.659.7[农业科学—基础兽医学]