Inhibition of dexamethasone-induced apoptosis in rat thymocytes by herbimycin A

• Published in: Japanese Journal of Pharmacology Vol. 64; no. suppl.1; p. 97
• Main Authors: Lee, Eibai, Kariya, Kimio
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1994
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)50030-0

Effect of herbimycin A, an inhibitor of tyrosine kinase, on apoptosis induced by dexamethasone (DEX) was examined in rat thymocytes. DNA fragmentation was increased by the treatment of thymocytes with 1 μM DEX. The addition of herbimycin A (0.1-1 μM) inhibited the increase of DNA fragmentation induced by DEX in a concentration-dependent manner. In addition, the release of lactate dehydrogenase (LDH) to the medium and chromatin cleavage caused by DEX were prevented by herbimycin A. No effects of other inhibitors of tyrosine kinase such as genistein and tyrphostin on the increase in DNA fragmentation and LDH release induced by DEX were observed, indicating that inhibition of apoptosis induced by DEX may be a specific action of herbimycin A among tyrosine kinase inhibitors. Although inhibitors of topoisomerase such as camptothecin and etoposide also induced apoptosis, herbimycin A had no effect on DNA fragmentation and LDH release induced by camptothecin or etoposide. These results indicate that herbimycin A selectively inhibited apoptosis induced by DEX but not by topoisomerase inhibitors. Therefore, herbimycin A is likely to be useful for studies on the mechanism of DEX-induced apoptosis.