Jiang Guohong, Wang Changming, Zhang Jun, Liu Haijun
Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563003, P.R. China.
Exp Ther Med. 2017 Jun;13(6):2763-2766. doi: 10.3892/etm.2017.4320. Epub 2017 Apr 10.
The aim of the study was to examine the mediation of insulin growth factor-1 (IGF-1) in Alzheimer's disease (AD), as well as the underlying mechanism of the PRNP genetic expression and PI3K/Akt signaling pathway. The Aβ-incubated rat adrenal pheochromocytoma cell (PC12) was established, constituting the AD model. Different doses (0, 20, 40 and 80 ng/ml) of IGF-1 were used in PC12 cells and the level of PRNP mRNA was tested after 24 h using the quantitative PCR method and the level of APP protein was assessed using western blot analysis. PC12 cells were divided into the control group (PC12 cells without Aβ treatment), model group (PC12 cells with Aβ treatment), IGF-1 80 ng/ml group, IGF-1 80 ng/ml+PI3K inhibitor LY294002 25 µmol/l group, and IGF-1 80 ng/ml+LY294002 50 µmol/l group, whose PRNP mRNA level and Akt, pAkt and APP protein level were tested 24 h later. As the dose of IGF-1 increases, the expression levels of PRNP mRNA and APP protein were more highly expressed. The difference between them was significant (P<0.05). In addition, regarding Akt protein, the expression levels of PRNP mRNA, APP protein and pAkt protein in the IGF-1 groups were significantly higher than those in the control and model groups. With the LY concentration increasing, the levels of expression of the three substances gradually decreased significantly (P<0.05). In conclusion, IGF-I can mediate the expression of the gene and APP protein through the PI3K/Akt signaling pathway, in a rat model.
本研究旨在探讨胰岛素样生长因子-1（IGF-1）在阿尔茨海默病（AD）中的介导作用，以及PRNP基因表达和PI3K/Akt信号通路的潜在机制。建立了经Aβ孵育的大鼠肾上腺嗜铬细胞瘤细胞（PC12），构成AD模型。在PC12细胞中使用不同剂量（0、20、40和80 ng/ml）的IGF-1，24小时后采用定量PCR法检测PRNP mRNA水平，并采用蛋白质免疫印迹分析评估APP蛋白水平。PC12细胞分为对照组（未用Aβ处理的PC12细胞）、模型组（用Aβ处理的PC12细胞）、IGF-1 80 ng/ml组、IGF-1 80 ng/ml + PI3K抑制剂LY294002 25 μmol/l组和IGF-1 80 ng/ml + LY294002 50 μmol/l组，24小时后检测其PRNP mRNA水平以及Akt、pAkt和APP蛋白水平。随着IGF-1剂量增加，PRNP mRNA和APP蛋白的表达水平更高。两者之间差异显著（P<0.05）。此外，关于Akt蛋白，IGF-1组中PRNP mRNA、APP蛋白和pAkt蛋白的表达水平显著高于对照组和模型组。随着LY浓度增加，这三种物质的表达水平逐渐显著降低（P<0.05）。总之，在大鼠模型中，IGF-I可通过PI3K/Akt信号通路介导基因和APP蛋白的表达。
