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

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 (Δφ_m). The drugs stimulated dexamethasone- and etoposide-induced apoptosis with the enhanced collapse of Δφ_m. The central-type benzodiazepines had no effect on either the Δφ_m or apoptosis. The reduction of Δφ_m 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 Δφ_m.