Involvement of histone hyperacetylation in triggering DNA fragmentation of rat thymocytes undergoing apoptosis

FEBS Letters

Miyabe, Takashi²  Lee, Eibai²  Yamauchi, Aiko¹  Furukubo, Taku²  Kariya, Kimio² 

[1] Department of Clinical Pharmacy, Faculty of Pharmaceutial Sciences, Kobe-Gakuin University, Nishi-ku, Kobe 651-21, Japan;Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Ikawadani-cho, Nishi-ku, Kobe 651-21, Japan

关键词: Histone hyperacetylation;    Apoptosis;    DNA fragmentation;    Thymocyte;    Chromatin structure;   

DOI  :  10.1016/0014-5793(96)01033-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown