INTERNAL CA2+ MOBILIZATION IS ALTERED IN FIBROBLASTS FROM PATIENTS WITH ALZHEIMER-DISEASE
INTERNAL CA2+ MOBILIZATION IS ALTERED IN FIBROBLASTS FROM PATIENTS WITH ALZHEIMER-DISEASE
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DOI：
10.1073/pnas.91.2.534
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发表时间：
1994-01-18
影响因子：
11.1
通讯作者：
ALKON, DL
中科院分区：
文献类型：
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作者：
ITO, E;OKA, K;ALKON, DL
最近有关阿尔茨海默病(AD)患者成纤维细胞KF通道功能障碍的研究和过去对记忆储存过程中钙离子介导的K+通道调节的观察表明，以记忆丧失和其他认知障碍为特征的AD也可能与细胞内钙动员功能障碍有关。与对照组的成纤维细胞相比，蛙皮素诱导的钙离子释放在AD成纤维细胞中被显著增强。另一种磷脂酶C激活剂缓激肽在AD成纤维细胞中也能引起类似的钙信号增强。相比之下，thapsigargin，一种通过直接作用于内质网释放钙离子的试剂，在AD和对照组成纤维细胞中没有引起钙离子增加的差异。去极化引起的钙离子内流数据先前表明，组间在钙泵和/或缓冲方面没有差异。组织培养传代次数与观察到的钙离子反应之间没有相关性。此外，所有组的细胞都以相同的密度接种并进行分析。放射配基结合实验表明，蛙皮素受体的数量和亲和力不能解释观察到的差异。这些和以前的观察表明，在成纤维细胞和其他细胞类型中蛙皮素和缓激肽反应的差异可能是由于三磷酸肌醇介导的细胞内钙释放的改变。
The recent demonstration of Kf channel dysfunction in fibroblasts from Alzheimer disease (AD) patients and past observations of Ca2+-mediated K+ channel modulation during memory storage suggested that AD, which is characterized by memory loss and other cognitive deficits, might also involve dysfunction of intracellular Ca2+ mobilization. Bombesin-induced Ca2+ release, which is inositol trisphosphate-mediated, is shown here to be greatly enhanced in AD fibroblasts compared with fibroblasts from control groups. Bradykinin, another activator of phospholipase C, elicits similar enhancement of Ca2+ signaling in AD fibroblasts. By contrast, thapsigargin, an agent that releases Ca2+ by direct action on the endoplasmic reticulum, produced no differences in Ca2+ increase between AD and control fibroblasts. Depolarization-induced Ca2+ influx data previously demonstrated the absence of between-group differences of Ca2+ pumping and/or buffering. There was no correlation between the number of passages in tissue culture and the observed Ca2+ responses. Furthermore, cells of all groups were seeded and analyzed at the same densities. Radioligand binding experiments indicated that the number and affinity of bombesin receptors cannot explain the observed differences. These and previous observations suggest that the differences in bombesin and bradykinin responses in fibroblasts and perhaps other cell types are likely to be due to alteration of inositol trisphosphate-mediated release of intracellular Ca2+.