Jpn. J. Pharmacol. 79 (2), 177-183 (1999)

Benzodiazepine Receptor Agonists Modulate Thymocyte Apoptosis Through Reduction of the Mitochondrial Transmembrane Potential

Yutaka Tanimoto, Yoshiaki Onishi, Yutaka Sato and Harutoshi Kizaki

Department of Biochemistry, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-0011, Japan

Abstract: Peripheral-type benzodiazepines have been shown to exert immunological effects. In this study, we examined the effects of the peripheral-type benzodiazepines on murine thymocytes. Murine thymocytes that were incubated with the peripheral-type benzodiazepines underwent apoptosis associated with the collapse of mitochondrial transmembrane potential (delta/psim). The drugs stimulated dexamethasone- and etoposide-induced apoptosis with the enhanced collapse of delta/psim. The central-type benzodiazepines had no effect on either the delta/psim or apoptosis. The reduction of delta/psim depended on protein synthesis and protein phosphorylation. These results suggest that the immunomodulating effect of benzodiazepines is in part due to the modulation of thymocyte apoptosis associated with the collapse of delta/psim.

Keywords: Benzodiazepine, Thymocyte, Mitochondrial permeability transition, Proteasome, Apoptosis

Copyrightę The Japanese Pharmacological Society 1999

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