中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (1): 178-183.doi: 10.4103/1673-5374.264473

• 原著:退行性病与再生 • 上一篇    

阿尔茨海默病患者红细胞中20S蛋白酶体和乙二醛酶1的活性降低

  

  • 出版日期:2020-01-15 发布日期:2020-05-22
  • 基金资助:

    国家自然科学基金项目（81860244）；广西壮族自治区自然科学基金项目（2018JJA140311，2018GXNSFAA281051）；广西壮族自治区中青年教师基础能力提升计划（2017KY0516）

20S proteasome and glyoxalase 1 activities decrease in erythrocytes derived from Alzheimer’s disease patients

Hui Lv, Gui-Yuan Wei, Can-Shou Guo, Yu-Feng Deng, Yong-Ming Jiang, Ce Gao, Chong-Dong Jian   

  1. Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang Autonomous Region, China
  • Online:2020-01-15 Published:2020-05-22
  • Contact: Chong-Dong Jian, PhD,jianchongdong02@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81860244; the Natural Science Foundation of Guangxi Zhuang Autonomous Region of China, No. 2018JJA140311 and 2018GXNSFAA281051; the Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi Zhuang Autonomous Region of China, No. 2017KY0516 (all to CDJ).

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摘要：

由于阿尔茨海默病患者大脑中大量积累甲基乙二醛和晚期糖化终产物，因而也被认为是是一种蛋白沉淀性疾病，而泛素蛋白酶体体系是降解蛋白的最重要途径之一，对于维持神经系统的正常生理功能十分重要。病例对照试验于2014/2017年在中国广西百色右江民族医学院附属医院招募了48例阿尔茨海默病患者(20男，28女，年龄75±6岁)以及50名健康志愿者（21男，29女，年龄72±7岁），以比色法检测血浆丙二醛和过氧化氢水平，采用分光光度法检测乙二醛酶1的活性，以荧光底物法测量红细胞中20S蛋白酶体活性，以Western blot分析检测红细胞膜中泛素和乙二醛酶1的蛋白表达水平。发现与对照组相比，阿尔茨海默病患者血浆丙二醛和过氧化氢水平升高，乙二醛酶1的活性降低，但乙二醛酶1的蛋白表达水平没有变化，而红细胞中20S蛋白酶体活性降低，泛素蛋白表达水平增加。结果提示蛋白酶体和乙二醛酶活性可能参与阿尔茨海默病的发生，且红细胞可能是阿尔茨海默病研究的良好对象。试验于2017年5月3日经右江民族医学院伦理委员会批准，批准号YJ12017013。

orcid: 0000-0002-1209-1248 (Chong-Dong Jian)

关键词: 20s蛋白酶体, 乙二醛酶1, 阿尔茨海默病, 泛素, 红细胞, 丙二醛, 过氧化氢, 神经退行性变, 神经再生

Abstract: As a result of accumulating methylglyoxal and advanced glycation end products in the brains of patients with Alzheimer’s disease, it is considered a protein precipitation disease. The ubiquitin proteasome system is one of the most important mechanisms for cells to degrade proteins, and thus is very important for maintaining normal physiological function of the nervous system. This study recruited 48 individuals with Alzheimer’s disease (20 males and 28 females aged 75 ± 6 years) and 50 healthy volunteers (21 males and 29 females aged 72 ± 7 years) from the Affiliated Hospital of Youjiang Medical University for Nationalities (Baise, China) between 2014 and 2017. Plasma levels of malondialdehyde and H2O2 were measured by colorimetry, while glyoxalase 1 activity was detected by spectrophotometry. In addition, 20S proteasome activity in erythrocytes was measured with a fluorescent substrate method. Ubiquitin and glyoxalase 1 protein expression in erythrocyte membranes was detected by western blot assay. The results demonstrated that compared with the control group, patients with Alzheimer’s disease exhibited increased plasma malondialdehyde and H2O2 levels, and decreased glyoxalase 1 activity; however, expression level of glyoxalase 1 protein remained unchanged. Moreover, activity of the 20S proteasome was decreased and expression of ubiquitin protein was increased in erythrocytes. These findings indicate that proteasomal and glyoxalase activities may be involved in the occurrence of Alzheimer’s disease, and erythrocytes may be a suitable tissue for Alzheimer’s disease studies. This study was approved by the Ethics Committee of Youjiang Medical University for Nationalities (approval No. YJ12017013) on May 3, 2017.

Key words: 20S proteasomal activity, Alzheimer’s disease, erythrocytes, glyoxalase 1, H2O2, malondialdehyde, nerve regeneration, total ubiquitin