Involvement of histone acetylation in triggering thymocytes apoptosis

• Published in: Japanese Journal of Pharmacology Vol. 67; no. suppl.1; p. 104
• Main Authors: Lee, Eibai, Furukubo, Taku, Kariya, Kimio
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1995
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)46381-6

Recently much attention has been focused on the molecular mechanism of apoptosis. However, little is known about the mechanism of internucleosomal DNA fragmentation which is a biochemical characteristic of apoptosis. The present study was designed to elucidate the role of histone, a major component of chromatin, in induction of apoptosis. The treatment of rat thymocytes with butylate and trichostatin A, which are inhibitors of histone deacetylase, resulted in an increased in DNA fragmentation. The increase in DNA fragmentation by these compounds was dependent on their concentrations and incubation time. The analysis of fragmented DNA by agarose gel electrophoresis showed DNA ladders, indicating that DNA was internucleosomally degraded. Butylate and trichostatin A also produced approximately 50 kbp DNA fragments, another characteristic feature of apoptotic cell death. In addition, morphological change in apoptosis such as nuclear condensation analyzed by laser scanning microscopy using Hoechst 33342, which is a DNA binding fluorescent dye, was observed in thymocytes treated with these compounds. These results demonstrate that butylate and trichostatin A induce thymocyte apoptosis. During the study on the mechanism of induction of apoptosis by these compounds, we confirmed that acetylation of histone was increased by butylate or trichostatin A. Therefore, it is possible that acetylation of histones induces thymocyte apoptosis. The role of histones in triggering apoptosis will be discussed.