Calyculin A, a potent inhibitor of phosphatases-1 and -2A, prevents apoptosis.

Calyculin A, a potent inhibitor of phosphatases-1 and -2A, prevents apoptosis.
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Calyculin A 是磷酸酶-1 和-2A 的有效抑制剂,可防止细胞凋亡。

DOI:
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发表时间:
1993
期刊:
Biochemical and Biophysical Research Communications - BBRC
影响因子:
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通讯作者:
M. Lavin
M. Lavin
中科院分区:
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文献类型:
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作者:
Qizhong Song;M. Lavin

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将伯基特淋巴瘤细胞系 BM13674 细胞暴露于伽马辐射或热会导致广泛的 DNA 断裂和细胞凋亡特征的形态变化。当细胞在花萼蛋白 A(磷酸酶 1 和 2A 催化亚基的有效抑制剂)存在下接受 γ 射线照射时,细胞凋亡被阻止。这显示出浓度依赖性,最大抑制发生在 20nM。通过与花萼蛋白 A 一起孵育,可以防止 DNA 断裂和细胞凋亡的形态特征。抑制细胞凋亡所需的浓度 (20 nM) 远低于之前报道的冈田酸 (500 nM),冈田酸也是磷酸酶活性和细胞凋亡的抑制剂。此外,虽然大田酸在对照细胞和受辐射细胞中引起核物质显着浓缩,同时防止细胞凋亡,但在花萼蛋白 A 存在的情况下,染色质没有明显的变化。从这些数据和蛋白质合成抑制剂的其他结果可以清楚地看出,在某些条件下诱导的细胞凋亡的完整机制预先存在于细胞中,磷酸酶活性在此过程中起着关键作用。
Exposure of the Burkitt's lymphoma cell line BM13674 cells to gamma-radiation or heat results in extensive DNA fragmentation and morphological changes characteristic of apoptosis. When cells were gamma-irradiated in the presence of calyculin A, a potent inhibitor of the catalytic subunit of phosphatases 1 and 2A, apoptosis was prevented. This was shown to be concentration dependent with maximal inhibition occurring at 20nM. Both DNA fragmentation and the morphological features characteristic of apoptosis were prevented by incubation with calyculin A. The concentration required to inhibit apoptosis (20 nM) was considerably less than that reported previously for okadaic acid (500 nM), also an inhibitor of phosphatase activity as well as apoptosis. In addition, while okadaic acid caused a marked condensation of nuclear material in both control and irradiated cells, while preventing apoptosis, no such changes in chromatin were evident in the presence of calyculin A. It is clear from these data and other results with protein synthesis inhibitors that the complete machinery for apoptosis, induced under certain conditions, preexists in the cell, and phosphatase activity plays a key role in this process.