Pathogenic amyloid β-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells
Pathogenic amyloid β-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells
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DOI：
10.3109/13506129909007321
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发表时间：
1999-09-01
期刊：
影响因子：
--
通讯作者：
Van Nostrand, WE
中科院分区：
文献类型：
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作者：
Davis, J;Cribbs, DH;Van Nostrand, WE
淀粉样β蛋白（A β）在阿尔茨海默病（AD）及其相关疾病（包括荷兰型淀粉样变性遗传性脑出血（HCMWA-D））患者脑内的脑血管和老年斑沉积中病理性蓄积。脑血管沉积物伴随着脑血管壁平滑肌细胞的变性和最终丧失。同样，我们已经证明致病形式的A β在体外培养的人脑血管平滑肌（HCSM）细胞中引起细胞死亡。在这里，我们发现致病性A β在HCSM细胞中诱导了许多结构变化，包括细胞体的收缩、突起的收缩、细胞内肌动蛋白网络的破坏以及核的凝聚和碎裂。这些变化伴随着一些生化改变的细胞核DNA的原位末端标记，平滑肌细胞肌动蛋白的蛋白水解分解，蛋白酶caspase 3的蛋白水解激活。总之，这些特征与HCSM细胞中响应于致病性A β的细胞死亡的凋亡机制一致。
The amyloid beta-protein (A beta) pathologically accumulates in cerebral vascular and senile plague deposits in the brains of patients with Alzheimer's disease (AD) and related dis. orders including hereditary cerebral hemorrhage with amyloidosis Dutch type (HCMWA-D). The cerebrovascular deposits are accompanied by degeneration and eventual loss of smooth muscle cells in cerebral vessel wall. Similarly, we have shown that pathogenic forms of A beta cause cell death in cultured human cerebrovascular smooth muscle (HCSM) cells in vitro. Here we show that pathogenic A beta induces a number of structural changes in HCSM cells Including shrinkage of cell bodies, retraction of processes, disruption of the intracellular actin network, and nuclear condensation and fragmentation. These changes were accompanied by a number of biochemical alterations in the cells shown by in situ end labeling of nuclear DNA, proteolytic breakdown of smooth muscle cell a actin, and proteolytic activation of the proteinase caspase 3. Together, these characteristics are consistent with an apoptotic mechanism of cell death in HCSM cells in response to pathogenic A beta.