中国比较医学杂志2011，Vol.21Issue(8)：15-19,5.DOI:10.3969/j.issn.1671-7856.2011.08.004
MicroRNA-153对靶基因下游信号分子GSK-3β表达水平及细胞抗损伤能力的影响
Effects of MicroRNA-153 on the Expression of Its Target Gene Downstream Signaling Molecule GSK-3β and on the Cellular Anti-Injury Ability
摘要
Abstract
Objective Mir-153 can negatively regulate the expression of APP and APLP2 protein, the crucial Alzheimer' s disease related genes, and consequently lower the level of their intracellular degradation fragment (intracellular domains, ICDs). Considering the transcriptional activity and pro-apoptotic role of ICDs, the aim of this study was to explore the effect of mir-153 on the expression of GSK-3β, the downstream signaling molecule of the two target genes, and on the ability of cells against damage stress to further identify the role of mir-153 in Alzheimer' s disease.Methods A stably transfected cell line over-expressing mir-153 was developed and mir-153 transgenic mice were generated. Western blot was used to detect the expression of phosphorylated GSK-3β, Tau and their total protein in the cells and mice. The mir-153 stably transfected cells were treated with Aβ42peptide and H202. respectively, to determine the changes of cell viability by MTS and analyze the cell apoptosis by flow cytometry. Results The expression of phosphorylated GSK-3β and it's total protein were decreased and the phosphorylation of Tau was reduced in the mir-153 stably transfected cells. The expression of phosphorylated GSK-3β and it' s total protein were down-regulated and the level of phosphorylated Tau and its total protein were not significantly changed in the brain of mir-153 transgenic mice. Under the treatment of Aβ42 peptide and H2O2, the viability of mir-153 stably transfected cells were clearly decreased and the apoptosis level of the cells was increased. Conclusion Mir-153 can negatively regulate the expression of GSK-3β, the downstream signaling molecule of its target genes. Over-expressed mir-153 lowers the cellular anti-injury ability.关键词
阿尔茨海默病/MicroRNA/GSK-3β/Tau/细胞凋亡Key words
Alzheimer's disease/MicroRNA/GSK-3β/Tau/Apoptosis/Mouse分类
医药卫生引用本文复制引用
梁春联,朱华,黄澜,许艳峰,邓巍,马春梅,刘颖,秦川..MicroRNA-153对靶基因下游信号分子GSK-3β表达水平及细胞抗损伤能力的影响[J].中国比较医学杂志,2011,21(8):15-19,5.基金项目
卫生部科研专项项目(200802036). （200802036）
