title: Caspase activation and cytochrome c release during HL-60 cell apoptosis induced by a nitric oxide donor.
abstract: Nitric oxide (NO) from (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate (NOC-18) induces apoptosis in human leukemia HL-60 cells. This effect was prevented by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK), thereby implicating caspase activity in the process. NOC-18 treatment resulted in the activation of several caspases including caspase-3, -6, -8, and -9(-like) activities and the degradation of several caspase substrates such as nuclear lamins and SP120 (hnRNP-U/SAF-A). Moreover, release of cytochrome c from mitochondria was also observed during NOC-18-induced apoptosis. This change was substantially prevented by Z-VAD-FMK, thereby suggesting that the released cytochrome c might function not only as an initiator but also as an amplifier of the caspase cascade. Bid, a death agonist member of the Bcl-2 family, was processed by caspases following exposure of cells to NOC-18, supporting the above notion. Thus, NO-mediated apoptosis in HL-60 cells involves a caspase/cytochrome c-dependent mechanism.
authors.affiliation: Institute of Medical Science, Kurashiki Medical Center, Okayama, Japan. JDG00551@nifty.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Yabuki
authors.forename: K
authors.initials: K
authors.lastname: Tsutsui
authors.forename: A A
authors.initials: AA
authors.lastname: Horton
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
authors.forename: K
authors.initials: K
authors.lastname: Utsumi
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism*; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology
chemical_list: D003574:Cytochrome c Group; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D020169:Caspases