Zhang Ming, Huo Dong-sheng, Cai Zhi-ping, Shao Guo, Wang He, Zhao Zhi-ying, Yang Zhan-jun
a Department of Anatomy , Baotou Medical College of Inner Mongolia University of Science and Technology , Inner Mongolia , China.
b Medical Research Center of Biomedicine , Baotou Medical College of Inner Mongolia University of Science and Technology , Inner Mongolia , China.
J Toxicol Environ Health A. 2015;78(21-22):1321-7. doi: 10.1080/15287394.2015.1085942. Epub 2015 Oct 29.
Disturbances in DNA methylation are postulated to result in various central nervous system diseases including Alzheimer's disease (AD). The SH-SY5Y neuronal cell line treated with Aβ1-40 (5 μmol/L) protein is considered to be a model of AD. Hence the aim of this study was to examine the influence of Schizandrol A, a plant extract, on DNA methylation in SH-SY5Y cells exposed to Aβ1-40. Aβ1-40 were incubated with varying concentrations of Sehizandrol A to a final concentration of 1 (low), 3 (intermediate) or 9 μg/ml (high). Exposure of SH-SY5Y with Aβ1-40 reduced viability, and altered cellular morphology and mRNA expression of DNA methyltransferase (DNMT3A) and DNMT3B. Treatment with 1 or 3 μg/ml Sehizandrol A resulted in normal cell morphology as well as elevated cell number, enhanced viability, and increased mRNA expression of DNMT3A and DNMT3B compared to saline. However, an increase in Sehizandrol A to 9 μg/ml produced a fall in cell viability, as well as a decrease in mRNA DNMT3A and DNMT3B expression to control levels. Data demonstrated that Schizandrol A at 1 or 3 μg/ml improved cell morphological appearance and viability of Aβ1-40 injured SH-SY5Y cells by an enhanced DNA methylation pathway.
据推测，DNA甲基化紊乱会导致包括阿尔茨海默病（AD）在内的各种中枢神经系统疾病。用Aβ1-40（5μmol/L）蛋白处理的SH-SY5Y神经母细胞瘤细胞系被认为是AD的模型。因此，本研究的目的是检测植物提取物五味子醇甲对暴露于Aβ1-40的SH-SY5Y细胞中DNA甲基化的影响。将Aβ1-40与不同浓度的五味子醇甲孵育，使其终浓度分别为1（低）、3（中）或9μg/ml（高）。用Aβ1-40处理SH-SY5Y细胞会降低细胞活力，并改变细胞形态以及DNA甲基转移酶（DNMT3A）和DNMT3B的mRNA表达。与生理盐水相比，用1或3μg/ml五味子醇甲处理可使细胞形态正常，细胞数量增加，活力增强，DNMT3A和DNMT3B的mRNA表达增加。然而，将五味子醇甲浓度增加到9μg/ml会导致细胞活力下降，以及DNMT3A和DNMT3B的mRNA表达降至对照水平。数据表明，1或3μg/ml的五味子醇甲通过增强DNA甲基化途径改善了Aβ1-40损伤的SH-SY5Y细胞的形态外观和活力。
