Tatebayashi Y, Takeda M, Kashiwagi Y, Okochi M, Kurumadani T, Sekiyama A, Kanayama G, Hariguchi S, Nishimura T
Department of Neuropsychiatry, Osaka University Medical School, Japan.
Dementia. 1995 Jan-Feb;6(1):9-16. doi: 10.1159/000106916.
Change in calcium response was studied to clarify the pathological process of Alzheimer's disease (AD). Cultured fibroblasts from patients with familial Alzheimer's disease (FAD; n = 6), sporadic Alzheimer's disease (SAD; n = 4), and age-matched healthy control subjects (n = 4) were studied with an ACAS Interactive Laser Cytometer (ACAS-470). Fibroblasts from two independent families with FAD (OS-1, and OS-2 families) showed a suppressed calcium response after stimulation by 100 nM bradykinin (BK) 100 nM vasopressin (VP) or 10% FCS in Ca(2+)-free condition compared with control fibroblasts at 48 h after plating. However, on the 7th day after plating, the abnormal calcium response was no longer observed. The height of the calcium peak showed periodic variation, indicating a relationship of calcium response with the cell cycle. When fibroblasts from OS-1 and OS-2 families were arrested in S phase, they showed a significantly suppressed calcium peak after BK stimulation. However, when those fibroblasts were arrested in other phases, they showed the same calcium peak as the other cells. The suppression of calcium response in S phase was indistinguishable from the calcium suppression induced by A23187 administration. Since Hardy type mutation on amyloid precursor protein gene is found in the OS-1 family, the observed abnormalities in calcium response might be related with pathological processing of amyloid precursor protein in AD. The reported abnormal calcium response, which is observed most obviously in fibroblasts in S phase, may indicate participation of the cell-cycle-dependent process in the pathology of AD.
研究钙反应的变化以阐明阿尔茨海默病（AD）的病理过程。使用ACAS交互式激光细胞仪（ACAS - 470）对来自家族性阿尔茨海默病（FAD；n = 6）、散发性阿尔茨海默病（SAD；n = 4）患者以及年龄匹配的健康对照者（n = 4）的培养成纤维细胞进行了研究。来自两个独立的FAD家族（OS - 1和OS - 2家族）的成纤维细胞在无钙条件下经100 nM缓激肽（BK）、100 nM血管加压素（VP）或10%胎牛血清（FCS）刺激后，与接种后48小时的对照成纤维细胞相比，钙反应受到抑制。然而，在接种后第7天，未再观察到异常钙反应。钙峰高度呈现周期性变化，表明钙反应与细胞周期有关。当来自OS - 1和OS - 2家族的成纤维细胞停滞在S期时，它们在BK刺激后显示出明显受抑制的钙峰。然而，当这些成纤维细胞停滞在其他阶段时，它们显示出与其他细胞相同的钙峰。S期钙反应的抑制与A23187给药诱导的钙抑制无明显差异。由于在OS - 1家族中发现了淀粉样前体蛋白基因的Hardy型突变，观察到的钙反应异常可能与AD中淀粉样前体蛋白的病理加工有关。所报道的异常钙反应在S期的成纤维细胞中最为明显，这可能表明细胞周期依赖性过程参与了AD的病理过程。
