Caspase activation and cytochrome c release during HL-60 cell apoptosis induced by a nitric oxide donor |
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Authors: | Munehisa Yabuki Ken Tsutsui Alan A. Horton Tamotsu Yoshioka Kozo Utsumi |
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Affiliation: | 1. Institute of Medical Science, Kurashiki Medical Center, 250 Bakuro-Cho, Kurashiki, Okayama, 710-8522, Japan;2. Department of Molecular Biology, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama, 700-8558, Japan;3. School of Biochemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom |
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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. |
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Keywords: | Nitric oxide apoptosis caspase cytochrome c Bid |
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