Peterson C, Ratan R R, Shelanski M L, Goldman J E
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Neurobiol Aging. 1988 May-Jun;9(3):261-6. doi: 10.1016/s0197-4580(88)80063-0.
Previous studies demonstrate that resting intracellular calcium in cultured skin fibroblasts declines due to in vivo aging and is further depressed by Alzheimer's disease. These data suggest that altered calcium homeostasis may underlie the deficits in cell function (e.g., cell spreading) that also occur in these cells. Depressed cytosolic free calcium in fibroblasts from aged and Alzheimer donors can be elevated by various drug treatments. 3,4-Diaminopyridine, serum, N-formyl-methionyl-leucyl-phenylalanine and bradykinin increased cytosolic free calcium transiently although the rate of the increase was slower and the magnitude of the rise was less in cells from aged and Alzheimer donors when compared to young donors. Four minutes after N-formyl-methionyl-leucyl-phenylalanine or bradykinin treatment cytosolic free calcium returned to resting levels in all six cell lines. Six minutes after either serum or 3,4-diaminopyridine treatments, however, cytosolic free calcium in cells from aged and Alzheimer donors remained elevated at concentrations similar to the resting calcium level in young cells. Bradykinin and serum were effective in the absence of extracellular calcium but 3,4-diaminopyridine and N-formyl-methionyl-leucyl-phenylalanine were not. These demonstrate that dynamic, as well as resting calcium homeostasis, is altered in cultured skin fibroblasts from aged and Alzheimer donors.
先前的研究表明，培养的皮肤成纤维细胞中的静息细胞内钙会因体内衰老而下降，并因阿尔茨海默病而进一步降低。这些数据表明，钙稳态的改变可能是这些细胞中也会出现的细胞功能缺陷（如细胞铺展）的基础。来自老年和阿尔茨海默病患者供体的成纤维细胞中胞质游离钙的降低可通过各种药物治疗来提高。3,4-二氨基吡啶、血清、N-甲酰甲硫氨酰亮氨酰苯丙氨酸和缓激肽可短暂增加胞质游离钙，尽管与年轻供体相比，老年和阿尔茨海默病患者供体细胞中钙增加的速率较慢且增加幅度较小。在N-甲酰甲硫氨酰亮氨酰苯丙氨酸或缓激肽处理4分钟后，所有六种细胞系中的胞质游离钙都恢复到静息水平。然而，在血清或3,4-二氨基吡啶处理6分钟后，老年和阿尔茨海默病患者供体细胞中的胞质游离钙仍保持升高，浓度与年轻细胞中的静息钙水平相似。缓激肽和血清在无细胞外钙的情况下有效，但3,4-二氨基吡啶和N-甲酰甲硫氨酰亮氨酰苯丙氨酸无效。这些结果表明，来自老年和阿尔茨海默病患者供体的培养皮肤成纤维细胞中的动态钙稳态以及静息钙稳态都发生了改变。
