Peterson C, Ratan R R, Shelanski M L, Goldman J E
Proc Natl Acad Sci U S A. 1986 Oct;83(20):7999-8001. doi: 10.1073/pnas.83.20.7999.
Aging and Alzheimer disease lead to alterations in calcium homeostasis. The concentration of cytosolic free calcium in cultured skin fibroblasts during aging and Alzheimer disease was determined with the calcium-sensitive fluorescent dyes quin-2 and fura-2. The Alzheimer donors showed a decline of 70% when compared to age-matched controls (P less than 0.001) and 81% when compared to cells from young adult donors (P less than 0.001). This reduction in quin-2-calcium fluorescence does not appear to be due to quenching by heavy metals or alterations in intracellular pH. Similar decreases in free cytosolic calcium were observed with fura-2. In addition, cells from aged and Alzheimer donors spread more slowly than those from young donors, and this deficit can be partially reversed by treatment with the calcium ionophore A23187. These studies agree with accumulating evidence that, at the cellular level, Alzheimer disease is a systemic, as well as cerebral, disease. The precise molecular basis of the decreased cytosolic calcium in fibroblasts is unknown, but there is evidence that it may be pathophysiologically important.
衰老和阿尔茨海默病会导致钙稳态的改变。使用钙敏感荧光染料喹啉-2和氟罗-2测定衰老和阿尔茨海默病患者培养的皮肤成纤维细胞中游离钙离子的浓度。与年龄匹配的对照组相比，阿尔茨海默病患者的细胞中喹啉-2钙荧光下降了70%（P<0.001），与年轻成年供体的细胞相比下降了81%（P<0.001）。喹啉-2钙荧光的这种降低似乎不是由于重金属淬灭或细胞内pH值的改变。使用氟罗-2也观察到游离细胞质钙有类似的下降。此外，衰老和阿尔茨海默病供体的细胞比年轻供体的细胞铺展得更慢，这种缺陷可以通过钙离子载体A23187处理得到部分逆转。这些研究与越来越多的证据一致，即在细胞水平上，阿尔茨海默病是一种全身性疾病，也是一种脑部疾病。成纤维细胞中细胞质钙减少的确切分子基础尚不清楚，但有证据表明它可能在病理生理上很重要。
