PrP106-126诱导的N2a细胞神经毒性中神经营养因子受体p75NTR的表达变化研究

畜牧兽医学报 ›› 2009, Vol. 40 ›› Issue (3): 416-420.doi:

PrP106-126诱导的N2a细胞神经毒性中神经营养因子受体p75^NTR的表达变化研究

白瑜¹，李玉荣^1,2，周向梅¹，尹晓敏¹，赵德明¹*

1. 中国农业大学动物医学院，北京 100193；2. 河北农业大学动物科技学院，保定 071001

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2009-03-24 发布日期:2009-03-24
通讯作者: 赵德明

Altered Expression of Neurotrophin Receptor p75^NTR in PrP106-126-induced Neurotoxicity of N2a cells

BAI Yu¹, LI Yu-rong^1,2, ZHOU Xiang-mei¹, YIN Xiao-min¹, ZHAO De-ming¹*

1.National Animal TSE Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China；2. College of Animal Science and Technology, Agricultural University of Hebei, Baoding 071001, China

Received:1900-01-01 Revised:1900-01-01 Online:2009-03-24 Published:2009-03-24

摘要/Abstract

摘要： 神经元死亡是朊病毒病的主要病理学特征。朊蛋白多肽PrP106-126能够对神经细胞表现神经毒性，引起细胞凋亡。细胞表面蛋白神经营养因子受体p75NTR的胞外区域可以与PrP106-126结合并产生促凋亡作用。作者以小鼠成神经瘤细胞N2a为细胞模型，应用荧光定量RT-PCR和Western Blot技术，以及DNA Ladder和Annexin V-FITC / PI双重染色流式细胞凋亡检测技术对p75^NTR介导的PrP106-126神经毒性分子机制进行了研究。结果发现在PrP106-126诱导的N2a细胞凋亡过程中，p75^NTR的mRNA转录水平和蛋白表达水平均显著升高，以p75^NTR多克隆抗体sc-6189阻断PrP 106-126与p75^NTR的相互作用后，减弱了PrP106-126诱导的N2a细胞凋亡效果。该研究揭示了PrP106-126诱导的N2a细胞毒性中p75^NTR受体的表达变化，为解释朊病毒病的发病机制提供了重要数据。

Abstract: Neuronal death is a pathological hallmark of prion diseases. Synthetic prion peptide PrP106-126 can cause neurotoxicity and induce apoptosis in neuronal cells. Extracellular region of neurotrophin receptor p75NTR, a cell surface protein, could bind to PrP106-126 and has apoptotic effect on neurons. Using quantitative RT-PCR， Western Blot technique, DNA Ladder assay, and flow cytometry (FCM) assay with Annexin V-FITC/PI doublestained, we investigated the p75NTRmediated neurotoxicity by PrP106126 in mouse neuroblastoma cells N2a. The results showed that in PrP106126-induced apoptosis of N2a cells, p75^NTR expression was significantly upregulated at mRNA and protein levels, and blocking the interaction of p75NTR with PrP 106-126 by p75^NTR polyclone antibody sc-6189 attenuated the apoptotic effect induced by PrP106-126. This study showed that mRNA and protein expression of receptor p75^NTR were altered in PrP106-126-induced neurotoxicity of N2a cells, and this may partially account for the pathogenesis of prion disease.

白瑜;李玉荣;周向梅;尹晓敏;赵德明. PrP106-126诱导的N2a细胞神经毒性中神经营养因子受体p75^NTR的表达变化研究[J]. 畜牧兽医学报, 2009, 40(3): 416-420.

BAI Yu;LI Yu-rong;ZHOU Xiang-mei;YIN Xiao-min;ZHAO De-ming . Altered Expression of Neurotrophin Receptor p75^NTR in PrP106-126-induced Neurotoxicity of N2a cells[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2009, 40(3): 416-420.

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