Song Q, Lavin M F
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, Australia.
Biochem Biophys Res Commun. 1993 Jan 15;190(1):47-55. doi: 10.1006/bbrc.1993.1009.
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.
将伯基特淋巴瘤细胞系BM13674细胞暴露于γ射线或热环境中会导致广泛的DNA片段化以及凋亡特有的形态学变化。当细胞在钙调磷酸酶A（一种蛋白磷酸酶1和2A催化亚基的强效抑制剂）存在的情况下接受γ射线照射时，凋亡被阻止。这表现出浓度依赖性，在20nM时出现最大抑制作用。通过与钙调磷酸酶A孵育，DNA片段化和凋亡特有的形态学特征均被阻止。抑制凋亡所需的浓度（20nM）远低于先前报道的冈田酸（500nM），冈田酸也是一种磷酸酶活性抑制剂以及凋亡抑制剂。此外，虽然冈田酸在对照细胞和照射细胞中均导致核物质明显浓缩，同时阻止凋亡，但在钙调磷酸酶A存在的情况下，染色质没有明显变化。从这些数据以及蛋白质合成抑制剂的其他结果可以清楚地看出，在某些条件下诱导凋亡的完整机制预先存在于细胞中，磷酸酶活性在这一过程中起关键作用。
