中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (5): 519-525.doi: 10.4103/1673-5374.130079

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

转瞬轴突蛋白1启动脑胶质瘤细胞相关凋亡基因表达但不诱导凋亡

  

  • 收稿日期:2014-02-07 出版日期:2014-03-12 发布日期:2014-03-12

Transient axonal glycoprotein-1 induces apoptosis-related gene expression without triggering apoptosis in U251 glioma cells

Haigang Chang 1, 2, Shanshan Song 3, Zhongcan Chen 2, Yaxiao Wang 1, Lujun Yang 2, Mouxuan Du 2, Yiquan Ke 2, Ruxiang Xu 4, Baozhe Jin 1, Xiaodan Jiang 2   

  1. 1 Department of Neurosurgery, the First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China
    2 Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong Province, Department of Neurosurgery, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China
    3 Eight-year Programme, the First Clinical Medical College of Southern Medical University, Guangzhou, Guangdong Province, China
    4 Department of Neurosurgery, Military General Hospital of Beijing PLA, Beijing, China
  • Received:2014-02-07 Online:2014-03-12 Published:2014-03-12
  • Contact: Baozhe Jin, M.D., Department of Neurosurgery, the First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China, 13938765496@ 163.com. Xiaodan Jiang, M.D., Ph.D., Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong Province, Department of Neurosurgery, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, Guangdong Province, China, jiangxiao_dan@163.com.
  • Supported by:

    This work was supported by grants from the National Natural Science Foundation of China, No. 81171179, 81272439; the Key Sci-Tech Research Projects of Guangdong Province in China, No. 2008A030201019; and the Guangzhou Municipal Science and Technology Project in China, No. 09B52120112-2009J1-C418-2, No. 2008A1-E4011-6.

摘要:

课题组以往研究结果显示,瞬变轴突糖蛋白1可作为淀粉样前体蛋白的配体、增强淀粉样前体蛋白胞内段的释放并参与阿尔茨海默病的细胞凋亡过程。为此课题组提出用转瞬轴突蛋白1对U251胶质瘤细胞进行干预,希望验证其与脑胶质瘤细胞的关系。MTT及细胞毒力实验证实转瞬轴突蛋白1未抑制U251胶质瘤细胞的生长,却表现出一定促细胞生长效应;TUNEL凋亡实验亦未发现转瞬轴突蛋白1促进U251胶质瘤细胞的凋亡;实时定量PCR实验证实转瞬轴突蛋白1能明显上调U251胶质瘤细胞中淀粉样前体蛋白胞内段、p53及表皮生长因子受体mRNA的表达。尽管瞬变轴突糖蛋白1可上调胶质瘤细胞中凋亡相关基因的表达,但并未诱导脑胶质瘤细胞凋亡,相反可促进胶质瘤细胞的增殖。

关键词: 神经再生, 脑损伤, 胶质瘤细胞, 瞬变轴突糖蛋白1, 淀粉样前体蛋白胞内段, p53, 表皮生长因子受体, 国家自然科学基金

Abstract:

Previous studies show that transient axonal glycoprotein-1, a ligand of amyloid precursor protein, increases the secretion of amyloid precursor protein intracellular domain and is involved in apoptosis in Alzheimer’s disease. In this study, we examined the effects of transient axonal glycoprotein-1 on U251 glioma cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that transient axonal glycoprotein-1 did not inhibit the proliferation of U251 cells, but promoted cell viability. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that transient axonal glycoprotein-1 did not induce U251 cell apoptosis. Real-time PCR revealed that transient axonal glycoprotein-1 substantially upregulated levels of amyloid precursor protein intracellular C-terminal domain, and p53 and epidermal growth factor receptor mRNA expression. Thus, transient axonal glycoprotein-1 increased apoptosis-related gene expression in U251 cells without inducing apoptosis. Instead, transient axonal glycoprotein-1 promoted the proliferation of these glioma cells.

Key words: nerve regeneration, brain injury, glioma cells, transient axonal glycoprotein-1, APP intracellular domain, p53, epidermal growth factor receptor, NSFC grant, neural regeneration