title: Nitric oxide induces apoptosis via triggering mitochondrial permeability transition.
abstract: Nitric oxide (NO) induces apoptosis in thymocytes, peripheral T cells, myeloid cells and neurons. Here we show that NO is highly efficient in inducing mitochondrial permeability transition, thereby causing the liberation of apoptogenic factors from mitochondria which can induce nuclear apoptosis (DNA condensation and DNA fragmentation) in isolated nuclei in vitro. In intact thymocytes, NO triggers disruption of the mitochondrial transmembrane potential, followed by hypergeneration of reactive oxygen species, exposure of phosphatidyl serine on the outer plasma membrane leaflet, and nuclear apoptosis. Inhibitors of mitochondrial permeability transition such as bongkrekic acid and a cyclophilin D-binding cyclosporin A derivative, N-methyl-Val-4-cyclosporin A, prevent the mitochondrial as well as all post-mitochondrial signs of apoptosis induced by NO including nuclear DNA fragmentation and exposure of phosphatidylserine residues on the cell surface. These findings indicate that NO can cause apoptosis via triggering of permeability transition.
authors.affiliation: CNRS-UPR420, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Hortelano
authors.forename: B
authors.initials: B
authors.lastname: Dallaporta
authors.forename: N
authors.initials: N
authors.lastname: Zamzami
authors.forename: T
authors.initials: T
authors.lastname: Hirsch
authors.forename: S A
authors.initials: SA
authors.lastname: Susin
authors.forename: I
authors.initials: I
authors.lastname: Marzo
authors.forename: L
authors.initials: L
authors.lastname: Boscá
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione; D013950:Thymus Gland / Q000166:cytology
chemical_list: D009603:Nitroso Compounds; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D005978:Glutathione; D010396:Penicillamine