Pathogenic amyloid beta-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells.
Pathogenic amyloid beta-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells.
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发表时间：
1999
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通讯作者：
J. Davis;D. Cribbs;C. Cotman;W. V. Van Nostrand
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作者：
J. Davis;D. Cribbs;C. Cotman;W. V. Van Nostrand
淀粉样β蛋白(Aβ)在阿尔茨海默病(AD)和包括遗传性脑出血伴淀粉样变性荷兰型(HCHWA-D)在内的相关疾病患者的脑血管和脑内老年斑沉积中病理积聚。脑血管沉积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，在体外培养的人脑血管平滑肌(HCSM)细胞中，Aβ的致病形式会导致细胞死亡。在这里，我们显示了致病的Aβ诱导了HCSM细胞的一些结构变化，包括细胞体收缩，突起回缩，细胞内肌动蛋白网络的破坏，以及核凝集和碎裂。伴随着这些变化的是细胞核DNA的原位末端标记、平滑肌细胞α肌动蛋白的蛋白分解和蛋白水解酶caspase 3的激活。这些特征与HCSM细胞对致病性Aβ致病的细胞死亡的一种凋亡机制是一致的。
The amyloid beta-protein (A beta) pathologically accumulates in cerebral vascular and senile plaque deposits in the brains of patients with Alzheimer's disease (AD) and related disorders including hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWA-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.