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

20S proteasome and glyoxalase 1 activities decrease in erythrocytes derived from Alzheimer's disease patients
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阿尔茨海默病患者红细胞中 20S 蛋白酶体和乙二醛酶 1 活性降低

DOI:
10.4103/1673-5374.264473
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发表时间:
2020-01-01
影响因子:
6.1
通讯作者:
Jian, Chong-Dong
Jian, Chong-Dong
中科院分区:
医学2区
文献类型:
--
作者:
Lv, Hui;Wei, Gui-Yuan;Jian, Chong-Dong

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由于甲基乙二醛和晚期糖基化终产物在阿尔茨海默病患者的大脑中积累,它被认为是一种蛋白质沉淀病。泛素蛋白酶体系统是细胞降解蛋白质的重要机制之一,对维持神经系统的正常生理功能具有重要意义。本研究于2014年至2017年在右江民族医学院附属医院招募了48名阿尔茨海默病患者(男性20人,女性28人,年龄75 +/- 6岁)和50名健康志愿者(男性21人,女性29人,年龄72 +/- 7岁)。用比色法测定血浆丙二醛和H2O2水平,分光光度法测定乙二醛酶1活性。此外,用荧光底物法测定20S蛋白酶体在红细胞中的活性。western blot法检测红细胞膜中泛素和乙草醛酶1蛋白的表达。结果表明,与对照组相比,阿尔茨海默病患者血浆丙二醛和H2O2水平升高,乙醛酶1活性降低;而glyoxalase 1蛋白的表达水平保持不变。红细胞20S蛋白酶体活性降低,泛素蛋白表达升高。这些发现表明,蛋白酶体和乙二醛酶活性可能参与阿尔茨海默病的发生,红细胞可能是阿尔茨海默病研究的合适组织。
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.