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