Sandhu F A, Kim Y, Lapan K A, Salim M, Aliuddin V, Zain S B
Department of Biochemistry and Cancer Center, University of Rochester School of Medicine, NY 14642, USA.
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2180-5. doi: 10.1073/pnas.93.5.2180.
The amyloid precursor protein (APP) is a molecule centrally involved in Alzheimer disease pathology, but whose normal function is still poorly understood. To investigate the consequences of increased intracellular production of various regions of APP on cellular physiology, we stably transfected PC12 cells with the C-terminal 100 amino acids of the human APP. In eight transfected clones that express the APP(C100) protein, exposure to nerve growth factor (NGF) did not promote differentiation. Transfectants continued to divide and failed to elaborate extensive neurites, whereas control PC12 cells, mock-transfected PC12 cells, and a nonexpressing transfected cell line did develop neurites and stopped dividing after NGF stimulation. Unlike NGF treatment, treatment with basic fibroblast growth factor profoundly accelerated neurite outgrowth in transfected cells. Also, a dramatic increase in a tyrosine phosphatase activity was noted. Expression and accumulation of APP C100 protein in PC12 cells results in an abnormal response to growth factor stimulation.
淀粉样前体蛋白（APP）是一种在阿尔茨海默病病理学中起核心作用的分子，但其正常功能仍知之甚少。为了研究APP不同区域细胞内产量增加对细胞生理学的影响，我们用人类APP的C末端100个氨基酸稳定转染PC12细胞。在八个表达APP（C100）蛋白的转染克隆中，暴露于神经生长因子（NGF）并未促进分化。转染细胞继续分裂，未能形成广泛的神经突，而对照PC12细胞、mock转染的PC12细胞和一个不表达的转染细胞系在NGF刺激后确实形成了神经突并停止分裂。与NGF处理不同，碱性成纤维细胞生长因子处理显著加速了转染细胞中的神经突生长。此外，还观察到酪氨酸磷酸酶活性显著增加。PC12细胞中APP C100蛋白的表达和积累导致对生长因子刺激的异常反应。
