阿尔茨海默病大脑中的CI - ATP酶和Na+/K(+) - ATP酶活性

CI-ATPase and Na+/K(+)-ATPase activities in Alzheimer's disease brains.

作者信息

Hattori N, Kitagawa K, Higashida T, Yagyu K, Shimohama S, Wataya T, Perry G, Smith M A, Inagaki C

机构信息

Department of Pharmacology, Kansai Medical University, Moriguchi-shi, Osaka, Japan.

出版信息

Neurosci Lett. 1998 Oct 2;254(3):141-4. doi: 10.1016/s0304-3940(98)00654-5.

DOI:10.1016/s0304-3940(98)00654-5

PMID:10214977

Abstract

The enzyme activities and the protein levels of Cl(-)-ATPase and Na+/K(+)-ATPase were examined in Alzheimer's disease (AD) brains. Cl(-)-ATPase and Na+/K(+)-ATPase activities in AD brains (n = 13) were significantly lower than those in age-matched control brains (n = 12). In contrast, there was no significant difference in anion-insensitive Mg2(+)-ATPase activity between the two groups. Western blot analysis revealed that the protein levels of Cl(-)-ATPase, Na+/K(+)-ATPase and neuron specific Na+/K(+)-ATPase alpha3 isoform were also significantly reduced in AD brains, while the amount of protein disulfide isomerase, one of the house keeping membrane proteins, was not different between the two groups. The data first demonstrated that Cl(-)-ATPase and Na+/K(+)-ATPase are selectively impaired in AD brains, which may reduce the gradients of Na(+), K(+) and Cl(-) across the cell membranes to cause excitotoxic cellular response and the resulting neuronal death.

摘要

在阿尔茨海默病（AD）患者的大脑中检测了氯离子 - ATP酶（Cl(-)-ATPase）和钠钾 - ATP酶（Na+/K(+)-ATPase）的酶活性及蛋白质水平。AD患者大脑（n = 13）中的Cl(-)-ATPase和Na+/K(+)-ATPase活性显著低于年龄匹配的对照大脑（n = 12）。相比之下，两组之间阴离子不敏感的镁离子 - ATP酶（Mg2(+)-ATPase）活性没有显著差异。蛋白质免疫印迹分析显示，AD患者大脑中Cl(-)-ATPase、Na+/K(+)-ATPase和神经元特异性Na+/K(+)-ATPase α3亚型的蛋白质水平也显著降低，而管家膜蛋白之一的蛋白质二硫键异构酶的含量在两组之间没有差异。这些数据首次表明，AD患者大脑中Cl(-)-ATPase和Na+/K(+)-ATPase受到选择性损害，这可能会降低细胞膜上钠、钾和氯离子的梯度，从而导致兴奋性毒性细胞反应及由此产生的神经元死亡。