title: Nitric oxide inhibits execution of apoptosis at two distinct ATP-dependent steps upstream and downstream of mitochondrial cytochrome c release.
abstract: The endogenous mediator nitric oxide (NO) blocked apoptosis of Jurkat cells elicited by staurosporine, anti-CD95 or chemotherapeutics, and switched death to necrosis. The switch in the mode of cell death was dependent on the ATP loss elicited by NO. This affected two distinct steps of the apoptotic cascade. First, the release of cytochrome c from mitochondria was delayed by NO. Second, processing of procaspases-3/7 to the active proteases was prevented even after cytochrome c had been released. Thus, NO interferes with execution steps of apoptosis both upstream and downstream of cytochrome c release.
authors.affiliation: Faculty of Biology, Department of Molecular Toxicology, University of Konstanz, Konstanz, D-78457, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Leist
authors.forename: B
authors.initials: B
authors.lastname: Single
authors.forename: H
authors.initials: H
authors.lastname: Naumann
authors.forename: E
authors.initials: E
authors.lastname: Fava
authors.forename: B
authors.initials: B
authors.lastname: Simon
authors.forename: S
authors.initials: S
authors.lastname: Kühnle
authors.forename: P
authors.initials: P
authors.lastname: Nicotera
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism
chemical_list: D003574:Cytochrome c Group; D020030:Nitric Oxide Donors; D010718:Phosphatidylserines; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D020169:Caspases