Benzodiazepine receptor agonists modulate thymocyte apoptosis through reduction of the mitochondrial transmembrane potential.
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 psi(m)). The drugs stimulated dexamethasone- and etoposide-induced apoptosis with the enhanced collapse of delta psi(m). The central-type benzodiazepines had no effect on either the delta psi(m) or apoptosis. The reduction of delta psi(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 delta psi(m).
Tanimoto
Y
Y
Department of Biochemistry, Tokyo Dental College, Chiba, Japan.
Onishi
Y
Y
Sato
Y
Y
Kizaki
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001665:Binding Sites; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D002998:Clonazepam / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D001570:Benzodiazepinones; D061945:Caspase Inhibitors; D058785:GABA-A Receptor Agonists; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D002998:Clonazepam; D005047:Etoposide; D003907:Dexamethasone; D003975:Diazepam