中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (27): 2573-2580.doi: 10.3969/j.issn.1673-5374.2013.27.009

• 原著:退行性病与再生 • 上一篇    下一篇

S14G-Humanin修复被淀粉样β蛋白扰乱的细胞稳定性

  

  • 收稿日期:2013-05-09 修回日期:2013-08-25 出版日期:2013-09-25 发布日期:2013-09-25

S14G-humanin restored cellular homeostasis disturbed by amyloid-beta protein

Xue Li1, 2, Wencong Zhao3, Hongqi Yang1, 2, Junhong Zhang1, 2, Jianjun Ma1, 2   

  1. 1 Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China

    2 Department of Neurology, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China

    3 Department of Pharmacology, Zhengzhou Maternal and Child Health Hospital, Zhengzhou 450012, Henan Province, China
  • Received:2013-05-09 Revised:2013-08-25 Online:2013-09-25 Published:2013-09-25
  • Contact: Xue Li, Master, Associate chief physician, dr.xue.li@ gmail.com.
  • Supported by:

    This study was supported by grants from Henan Medical Technologies R&D Program in China, No. 200703023, 201203130 and Henan Key Science and Technology Project in China, No. 112102310684.

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摘要：

淀粉样β蛋白（Aβ）在阿尔茨海默病的发病机制中起着重要作用。 Humanin（HN）是新近发现的可能对阿尔茨海默病具有治疗作用的蛋白质，其衍生物HNG（S14G-突变体）对阿尔茨海默病的神经保护活性比HN强1000倍。然而，HNG抗阿尔茨海默病功能的详细分子机制仍不清楚。我们使用荧光技术检测Aβ40和humanins对海马细胞的细胞膜流动性，细胞的钙稳态，线粒体膜电位和活性氧的影响。结果纤维状Aβ40降低膜流动性，增加细胞钙水平，产生活性氧和降低线粒体膜电位，通过细胞膜扰乱了细胞的静态平衡。HNG可恢复被纤维状Aβ40扰乱的这些变化，但被纤维状Aβ40降低的线粒体膜电位恢复较少。结果表明纤维状Aβ40是通过细胞膜作用于线粒体，即升高细胞内钙和活性氧的水平；而HNG阻断淀粉样β蛋白对膜的作用，而重建受干扰的细胞静态平衡。

关键词: 神经再生, 阿尔茨海默病, 淀粉样β蛋白, 野生型Humanin, S14G Humanin, 活性氧, 线粒体膜电位, 基金资助文章

Abstract:

Humanin is a potential therapeutic agent for Alzheimer’s disease, and its derivative, S14G-humanin, is 1 000-fold stronger in its neuroprotective effect against Alzheimer’s disease-relevant insults. Alt-hough effective, the detailed molecular mechanism through which S14G-humanin exerts its effects remains unclear. Data from this study showed that fibrillar amyloid-beta 40 disturbed cellular ho-meostasis through the cell membrane, increasing intracellular calcium, generating reactive oxygen species, and decreasing the mitochondrial membrane potential. S14G-humanin restored these re-sponses. The results suggested that S14G-humanin blocked the effects of amyloid-beta 40 on the neuronal cell membrane, and restored the disturbed cellular homeostasis, thereby exerting a neuroprotective effect on hippocampal neurons.

Key words: neural regeneration, Alzheimer’s disease, amyloid-beta protein, wild type humanin, S14G-humanin, re-active oxygen species, mitochondrial membrane potential, grants-supported paper, neurodegeneration, neuroregeneration