The role of mitochondria in nitric oxide-mediated thymocyte apoptosis.
The aim of this study was to analyze whether immunosuppressants could affect NO-induced thymocytes apoptosis. S-Nitroso-N-acetyl-D,L-penicillamine (SNAP, an NO donor) has an apoptotic effect on murine thymocytes. This NO-induced thymocyte apoptosis is associated with a reduced uptake of DiOC(6), a fluorochrome which incorporates into cells depending on their mitochondrial membrane potential (DeltaPsi(m)). The immunosuppressant, cyclosporin A, partially inhibited NO-induced thymocyte apoptosis as well as the reduction of DeltaPsi(m). In contrast, another immunosuppressant, FK506, did not affect NO-induced thymocyte apoptosis. Although FK506 and cyclosporin A inhibit T-cell signal transduction by the same mechanism, their effects on mitochondria may contribute to the differential apoptosis induction ability.
Migita
Kiyoshi
K
Clinical Research Center, National Nagasaki Medical Center, Kubara 2-1001-1, Omura 856-8652, Japan. migita@nmc.hosp.go.jp
Tanaka
Fumiko
F
Abiru
Seigo
S
Ida
Hiroaki
H
Izumi
Yasumori
Y
Kawakami
Atsushi
A
Eguchi
Katsumi
K
D000818:Animals; D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D005456:Fluorescent Dyes; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D016572:Cyclosporine; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases; D010396:Penicillamine; D016559:Tacrolimus