半胱天冬酶-9的过表达在体外引发其激活及细胞凋亡。
Overexpression of caspase-9 triggers its activation and apoptosis in vitro.
作者信息
Druskovic Mirjam, Suput Dusan, Milisav Irina
机构信息
Institute of Pathophysiology, Medical Faculty, Ljubljana, Slovenia.
出版信息
Croat Med J. 2006 Dec;47(6):832-40.
AIM
To investigate the consequences of increased expression of caspase-9: 1) whether the caspase-9 overexpression resulted in cell death through apoptosis, 2) whether apoptosis could be triggered in normal and tumor cells, and 3) what is the role of caspase-9 in the process.
METHODS
The caspase-9 fused to green fluorescent protein was expressed in primary cultures of anterior pituitary cells and of HeLa tumor cells. The expressed caspase-9 and the number of apoptotic and necrotic cells were determined using fluorescence microscopy.
RESULTS
Overexpression of caspase-9 resulted in cell death of primary pituitary cells and HeLa cells. More than 94% of the cells died of apoptosis, which was triggered by the activation of caspase-9, since the cell deaths were prevented in the presence of caspase-9 specific inhibitor. HeLa cells were about 50% more resistant to apoptosis than pituitary cells.
CONCLUSIONS
Caspase-9 overexpression and its activation leads to apoptosis. It occurs both in normal and tumor cells. Since the majority of cancer therapy treatments initiate apoptosis through the caspase-9 activation, the modulation of caspase-9 expression may be exploited in designing new ways to control apoptosis in neurodegenerative or malignant diseases.
目的
研究半胱天冬酶 -9表达增加的后果：1）半胱天冬酶 -9过表达是否通过凋亡导致细胞死亡；2）正常细胞和肿瘤细胞中是否能引发凋亡；3）半胱天冬酶 -9在此过程中的作用是什么。
方法
将与绿色荧光蛋白融合的半胱天冬酶 -9在前脑垂体细胞和人宫颈癌HeLa细胞的原代培养物中表达。使用荧光显微镜确定表达的半胱天冬酶 -9以及凋亡和坏死细胞的数量。
结果
半胱天冬酶 -9过表达导致原代垂体细胞和HeLa细胞死亡。超过94%的细胞死于凋亡，这是由半胱天冬酶 -9的激活引发的，因为在存在半胱天冬酶 -9特异性抑制剂的情况下细胞死亡被阻止。HeLa细胞对凋亡的抗性比垂体细胞高约50%。
结论
半胱天冬酶 -9过表达及其激活导致凋亡。它在正常细胞和肿瘤细胞中均会发生。由于大多数癌症治疗方法通过半胱天冬酶 -9激活引发凋亡，因此在设计控制神经退行性疾病或恶性疾病中凋亡的新方法时，可利用对半胱天冬酶 -9表达的调节。
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