中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1433-1440.doi: 10.4103/1673-5374.165511

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

氧糖剥夺诱导自噬机制可改善脑卒中后的认知功能

  

  • 收稿日期:2015-08-05 出版日期:2015-09-28 发布日期:2015-09-28
  • 基金资助:

    国家自然科学基金（31171014，31371065）

Oxygen-glucose deprivation regulates BACE1 expression through induction of autophagy in Neuro-2a/APP695 cells

Rong-fu Chen1, Ting Zhang1, Yin-yi Sun1, Ya-meng Sun1, Wen-qi Chen1, Nan Shi2, Fang Shen1, Yan Zhang2, Kang-yong Liu1, 2, Xiao-jiang Sun1   

  1. 1 Department of Neurology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
    2 Zhoupu Hospital, Pudong New District, Shanghai, China
  • Received:2015-08-05 Online:2015-09-28 Published:2015-09-28
  • Contact: Xiao-jiang Sun, Ph.D., sunxj155@sohu.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 31171014, 31371065; a grant from Shanghai Municipal Health Bureau, China, No. 20134125; a grant from Shanghai Pudong District Health Bureau of China, No. PDZz2013-10

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摘要：

本课题组以往研究发现，调节自噬可改善脑卒中小鼠的学习记忆能力，其作用与调节自噬以清除沉积在细胞外的β淀粉样蛋白有关，但具体机制不明，但推测该机制可能涉及β淀粉样蛋白代谢中的关键限速酶-β位剪切酶1的调节。为此，实验建立了氧糖剥夺脑缺血Neuro-2a/APP695细胞模型，观察自噬诱导剂雷帕霉素及自噬抑制剂3-甲基腺苷对β位剪切酶1蛋白表达的影响。发现氧糖剥夺及雷帕霉素可下调Neuro-2a/APP695细胞β位剪切酶1蛋白表达水平，而3-甲基腺苷可上调其蛋白的表达。证实氧糖剥夺通过诱导自噬起到抑制Neuro-2a/APP695细胞中淀粉样蛋白前体β位剪切酶1表达的作用，可能以此改善脑卒中后的认知功能。

关键词: 神经再生, 脑损伤, 氧糖剥夺, 脑缺血, 脑卒中, 自噬, β位剪切酶1, β-淀粉样肽, 3-甲基腺嘌呤, 雷帕霉素, 认知功能, 国家自然科学基金

Abstract:

Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide (Aβ) in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-cleaving enzyme 1 (BACE1), the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 (APP695) cell models of cerebral ischemia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin (an autophagy inducer) or 3-methyladenine (an autophagy inhibitor) on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.

Key words: nerve regeneration, brain Injury, oxygen-glucose deprivation, cerebral ischemia, stroke, autophagy, beta-site APP-cleaving enzyme 1 (BACE1), beta-amyloid peptide, 3-methyladenine (3-MA), Rapamycin, neural regeneration