Fang Bo-yan, Jia Jian-ping
Department of Neurology, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China.
Chin Med J (Engl). 2008 May 20;121(10):910-5.
Two novel presenilin 1 (PS1) mutations, V97L and A136G, were recently found to be involved in the early-onset of Alzheimer's disease in two Chinese families. This research aimed to verify their pathological effects.
The human neuroblastoma SH-SY5Y cells stably transfected with these two Chinese presenilin 1 mutations were established to explore whether they are sensitive to, or influenced by, serum deprivation and protected by insulin-like growth factor-1 (IGF-1). Apoptosis rate, glucose uptake of the cells and the expression of glucose transport protein 1 (GLUT1) on cell membranes were examined.
The V97L or A136G mutants significantly decreased the cells viability and increased the apoptosis rate when compare to PS1wt and mock transfected cells. IGF-1 was found to improve the viability of these two kinds of mutant cells significantly, and to show a protective effect for the mutants when they were treated with trophic deprivation. The glucose uptake of each transfected cell line increased to about 25% after IGF-1 treatment, GLUT1 expression on the cell membrane increased modestly by about 15% - 20%.
Enhanced sensitivity to trophic withdrawal in the cells transfected with the two Chinese PS1 mutations may contribute to the neuron apoptosis. IGF-1 provided a protective effect to cells, possibly through an enhanced glucose transport and mitochondrial activities.
最近发现两种新的早老素1（PS1）突变，V97L和A136G，与两个中国家庭早发性阿尔茨海默病有关。本研究旨在验证它们的病理作用。
建立稳定转染这两种中国早老素1突变的人神经母细胞瘤SH-SY5Y细胞，以探讨它们是否对血清剥夺敏感或受其影响，以及是否受胰岛素样生长因子-1（IGF-1）保护。检测细胞凋亡率、葡萄糖摄取以及细胞膜上葡萄糖转运蛋白1（GLUT1）的表达。
与野生型PS1和mock转染细胞相比，V97L或A136G突变体显著降低细胞活力并增加凋亡率。发现IGF-1可显著提高这两种突变体细胞的活力，并在它们受到营养剥夺处理时对突变体显示出保护作用。IGF-1处理后，各转染细胞系的葡萄糖摄取增加至约25%，细胞膜上GLUT1表达适度增加约15%-20%。
转染两种中国PS1突变的细胞对营养物质剥夺的敏感性增强可能导致神经元凋亡。IGF-1可能通过增强葡萄糖转运和线粒体活性为细胞提供保护作用。
