Slack B E, Nitsch R M, Livneh E, Kunz G M, Eldar H, Wurtman R J
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Ann N Y Acad Sci. 1993 Sep 24;695:128-31. doi: 10.1111/j.1749-6632.1993.tb23040.x.
Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration-dependent manner by phorbol 12-myristate 13-acetate. In fibroblasts overexpressing protein kinase C alpha (PKC alpha), the EC50 for this response was 7 nM, while in control cells the EC50 was 63 nM. The effect of PMA was inhibited by the PKC antagonist H-7 in control cells, but not in cells that overexpressed PKC alpha. Basal release of APP was higher in cells that overexpressed PKC alpha, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKC alpha regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.
佛波醇12 -肉豆蔻酸酯13 -乙酸酯以浓度依赖的方式刺激瑞士3T3成纤维细胞释放阿尔茨海默病的淀粉样前体蛋白（APP）。在过表达蛋白激酶Cα（PKCα）的成纤维细胞中，此反应的半数有效浓度（EC50）为7 nM，而在对照细胞中EC50为63 nM。在对照细胞中，PKC拮抗剂H - 7可抑制佛波酯（PMA）的作用，但在过表达PKCα的细胞中则不然。过表达PKCα的细胞中APP的基础释放量较高，且不受磷酸酶抑制剂冈田酸的影响，尽管该化合物使对照细胞的APP释放量增加了一倍。结果表明，PKCα调节哺乳动物细胞中APP的加工过程。据报道，PKC活性的改变发生在阿尔茨海默病中，可能会导致该疾病特有的APP代谢异常。
