Lee E, Furukubo T, Miyabe T, Yamauchi A, Kariya K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Kobe, Japan.
FEBS Lett. 1996 Oct 21;395(2-3):183-7. doi: 10.1016/0014-5793(96)01033-2.
The treatment of rat thymocytes with trichostatin A and sodium butyrate, which are inhibitors of histone deacetylase, resulted in an increase in DNA fragmentation in a concentration-dependent manner. A significant increase in DNA fragmentation induced by these compounds was observed after a lag time of 2 h. Analysis of the fragmented DNA revealed the production of approximately 50 kb DNA fragments and DNA ladders, the biochemical hallmarks of apoptotic cell death. Judging from a laser scanning microscopic analysis, the inhibitors of histone deacetylase induced nuclear condensation, the morphological feature of apoptosis. Biochemical and morphological analyses demonstrated that trichostatin A and sodium butyrate induced thymocyte apoptosis. Furthermore, hyperacetylation of nuclear histones was observed in thymocytes treated with the inhibitors of histone deacetylase. These effects of sodium butyrate and trichostatin A were seen 0.5 and 1 h, respectively, after incubation of the cells. These results thus indicate that hyperacetylation of nucleosomal histones precedes DNA fragmentation in thymocytes undergoing apoptosis induced by trichostatin A and sodium butyrate.
用组蛋白脱乙酰酶抑制剂曲古抑菌素A和丁酸钠处理大鼠胸腺细胞，会导致DNA片段化呈浓度依赖性增加。在2小时的延迟时间后，观察到这些化合物诱导的DNA片段化显著增加。对片段化DNA的分析显示产生了约50 kb的DNA片段和DNA梯形条带，这是凋亡细胞死亡的生化标志。从激光扫描显微镜分析来看，组蛋白脱乙酰酶抑制剂诱导了核浓缩，这是凋亡的形态学特征。生化和形态学分析表明曲古抑菌素A和丁酸钠诱导了胸腺细胞凋亡。此外，在用组蛋白脱乙酰酶抑制剂处理的胸腺细胞中观察到核组蛋白的高度乙酰化。在细胞孵育后，分别在0.5小时和1小时观察到丁酸钠和曲古抑菌素A的这些作用。因此，这些结果表明，在由曲古抑菌素A和丁酸钠诱导凋亡的胸腺细胞中，核小体组蛋白的高度乙酰化先于DNA片段化。
