Kitamura Y, Shimohama S, Kamoshima W, Ota T, Matsuoka Y, Nomura Y, Smith M A, Perry G, Whitehouse P J, Taniguchi T
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Brain Res. 1998 Jan 12;780(2):260-9. doi: 10.1016/s0006-8993(97)01202-x.
Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2 alpha, Bcl-xL, Bcl-x beta, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x beta was increased, while Bcl-xL, Bax, Bak, and Bad and ICH-1L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.
最近，细胞凋亡与阿尔茨海默病（AD）的选择性神经元丢失有关。细胞凋亡受B细胞淋巴瘤-2基因产物（Bcl-2）家族（Bcl-2、Bcl-x、Bax、Bak和Bad）和半胱天冬酶家族（ICH-1和CPP32）调控，其中Bcl-2和Bcl-x可阻止细胞凋亡，而Bax、Bak、Bad、ICH-1和CPP32则促进细胞凋亡。在本研究中，我们检测了AD患者和对照者大脑颞叶皮质膜性和胞质部分中这些蛋白质的水平。在膜性部分，AD患者中Bcl-2α、Bcl-xL、Bcl-xβ、Bak和Bad的水平升高。在胞质部分，Bcl-xβ水平升高，而Bcl-xL、Bax、Bak、Bad和ICH-1L则无变化。在AD患者或对照者大脑中均未检测到CPP32。这些发现表明细胞死亡调节蛋白在AD中的参与存在差异，并提示AD大脑中Bak、Bad、Bcl-2和Bcl-x上调。
