Lahiri D K, Nall C, Farlow M R
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202.
Biochem Int. 1992 Dec;28(5):853-60.
Amyloid beta-protein, the major constituent of amyloid plaques in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). Changes in the rates and or pathways of APP synthesis and degradation may be central to the deposition of beta-amyloid. We explored the possibility that APP processing is regulated by activation of endogenous cell-surface neurotransmitter receptors by stimulating C6, PC12 and neuroblastoma cells with the cholinergic agonist carbachol. We measured the intracellular APP in these cell lines by western blotting using three antibodies against different regions of APP. When cells were treated with carbachol for different periods, PC12 and C6 cells responded with a sharp decrease of APP bands. Similar blots probed with an antibody against heat-shock protein (HSP), showed no change in the intensity of the immunoreactive HSP-70 band. These results suggest that the decrease in intracellular APP seen after stimulation by carbachol has some specificity and that APP processing may be regulated by stimulation of cholinergic receptors on the surface of cells.
β-淀粉样蛋白是阿尔茨海默病中淀粉样斑块的主要成分，它源自更大的淀粉样前体蛋白（APP）。APP合成与降解的速率和/或途径的变化可能是β-淀粉样蛋白沉积的核心。我们探讨了APP加工是否受内源性细胞表面神经递质受体激活调节的可能性，方法是用胆碱能激动剂卡巴胆碱刺激C6、PC12和神经母细胞瘤细胞。我们使用三种针对APP不同区域的抗体，通过蛋白质印迹法测量这些细胞系中的细胞内APP。当细胞用卡巴胆碱处理不同时间时，PC12和C6细胞的APP条带急剧减少。用抗热休克蛋白（HSP）抗体检测的类似印迹显示，免疫反应性HSP-70条带的强度没有变化。这些结果表明，卡巴胆碱刺激后细胞内APP的减少具有一定特异性，并且APP加工可能受细胞表面胆碱能受体刺激的调节。
