中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (21): 1923-1928.doi: 10.4103/1673-5374.145362

• 原著:退行性病与再生 • 上一篇    下一篇

淀粉样前体类蛋白2-C端片段可上调BV2细胞中S100A9基因和蛋白的表达

  

  • 收稿日期:2014-09-06 出版日期:2014-11-15 发布日期:2014-11-15
  • 基金资助:

    国家自然科学基金（81160159）

Amyloid precursor-like protein 2 C-terminal fragments upregulate S100A9 gene and protein expression in BV2 cells

Guangzhe Li 1, Hui Chen 2, Lin Cheng 2, Rongjie Zhao 3, Junchang Zhao 3, Yanji Xu 2   

  1. 1 Department of Psychology, Yanbian Brain Hospital, Yanji, Jilin Province, China
    2 Department of Preventive Medicine, Medical College, Yanbian University, Yanji, Jilin Province, China
    3 Department of Pharmacology, Mudanjiang Medical University, Mudanjiang, Heilongjiang, China
  • Received:2014-09-06 Online:2014-11-15 Published:2014-11-15
  • Contact: Yanji Xu, Ph.D., Department of Preventive Medicine, Medical College, Yanbian University, Yanji 133002, Jilin Province, China, xuyanji@ybu.edu.cn.
  • Supported by:

    This work was supported by the Natural Science Foundation of Technology Gallery in Jilin Province of China, No. 2011-15237; and the National Natural Science Foundation of China, No. 81160159.

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摘要：

鉴于小鼠小胶质细胞 BV2即可对神经元起保护作用，又可间接分泌炎性细胞因子对神经元起毒性作用，是治疗神经炎症及神经退行性疾病的一个重要靶点。实验设想淀粉样类前体蛋白2-C端不同片段(Amyloid Precursor Like Protein 2-C Terminal Fragments，APLP2-CTFs) CT57、CT50、CT31观察其在BV2细胞中对S100A9表达的影响。实验将pEGFP-APLP2-CTFs(C57、C50、C31)转染到BV2细胞中，经过RT-PCR，western blot和免疫细胞化学染色检测发现，转染后BV2细胞中S100A9蛋白和mRNA表达均增高；进一步采用转染了全长APLP2-751 cDNA抑制淀粉样类前体蛋白2-C端片段的产生，发现BV2细胞中S100A9的蛋白表达下降。结果证实，APLP2-CTFs可上调BV2细胞中S100A9蛋白和mRNA的表达，此结果可为研究阿尔茨海默病的神经元损伤与凋亡及修复和保护提供了一条新的毒性通路。

关键词: 神经再生, 神经退行性变, 阿尔茨海默病, APLP2, S100A9, C端片段, 淀粉样前体蛋白, BV2细胞, γ-分泌酶, 国家自然科学基金

Abstract:

The murine microglial cell line BV2 has neuroprotective effects, but is toxic to neurons by secreting inflammatory cytokines, and is an important target in the treatment of nerve inflammation and neurodegenerative diseases. In the present study, we observed the effects of transfecting three amyloid precursor-like protein 2 (APLP2) C-terminal fragments (CTFs; C57, C50 and C31) in the pEGFP-N1 vector on S100A9 expression in BV2 cells. Reverse transcription-PCR, western blot assay and immunocytochemistry revealed that S100A9 protein and mRNA expression was greater in BV2 cells after CTF transfection than after mock transfection with an empty vector. Furthermore, transfection of full-length APLP2-751 resulted in low levels of S100A9 protein expression. Our results show that APLP2-CTFs upregulate S100A9 protein and mRNA expression in BV2 cells, and identify a novel pathway involved in neuronal injury and apoptosis, and repair and protection in Alzheimer’s disease.

Key words: nerve regeneration, neurodegeneration, Alzheimer’s disease, APLP2, S100A9, C-terminal fragments, amyloid precursor protein, BV2 cells, γ-secretase, NSFC grant, neural regeneration