McCoy K R, Mullins R D, Newcomb T G, Ng G M, Pavlínková G, Polinsky R J, Nee L E, Sisken J E
Department of Microbiology and Immunology, College of Medicine, University of Kentucky, Lexington 40536.
Neurobiol Aging. 1993 Sep-Oct;14(5):447-55. doi: 10.1016/0197-4580(93)90103-i.
The calcium-sensitive photoprotein, aequorin, was used to examine serum- and bradykinin-induced transient increases in free cytosolic calcium ions in skin fibroblasts from 10 individuals with early onset familial AD (FAD), including four who were biopsied before their clinical symptoms would allow a diagnosis of AD, 2 individuals with late onset FAD, 8 at-risk but nonsymptomatic individuals, and 13 controls. The data show that (a) among controls, the peaks of the calcium transients increase in height as a function of donor age; (b) transients induced by 10% serum, 10 nM bradykinin (BK) or 100 nM BK were generally lower in FAD fibroblasts, including those from donors in the early stages of the disease, than in age-matched control cells; (c) such transients are reduced in cells from a proportion of the nonsymptomatic, at-risk individuals. Thus, serum- and BK-induced calcium transients are reduced in fibroblasts from both early and more advanced stage FAD donors and perhaps even from donors who are presymptomatic carriers of the defective gene. The data also suggest that changes in calcium transients in FAD fibroblasts neither mimic nor exaggerate the effects of normal aging.
利用钙敏感光蛋白水母发光蛋白，检测了10例早发性家族性阿尔茨海默病（FAD）患者、2例晚发性FAD患者、8例有患病风险但无症状个体以及13名对照者皮肤成纤维细胞中血清和缓激肽诱导的游离胞质钙离子的短暂升高。其中，10例早发性FAD患者中有4例在临床症状出现前进行了活检，此时尚无法诊断为阿尔茨海默病（AD）。数据显示：（a）在对照组中，钙瞬变峰值随供体年龄增加而升高；（b）10%血清、10 nM缓激肽（BK）或100 nM BK诱导的瞬变在FAD成纤维细胞中通常低于年龄匹配的对照细胞，包括疾病早期供体的细胞；（c）一部分有患病风险但无症状个体的细胞中此类瞬变减少。因此，早发性和晚期FAD供体，甚至可能是缺陷基因无症状携带者供体的成纤维细胞中，血清和BK诱导的钙瞬变均减少。数据还表明，FAD成纤维细胞中钙瞬变的变化既不模拟也不夸大正常衰老的影响。
