Caspase activation and cytochrome c release during HL-60 cell apoptosis induced by a nitric oxide donor |
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Authors: | Yabuki M Tsutsui K Horton A A Yoshioka T Utsumi K |
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Institution: |
a Institute of Medical Science, Kurashiki Medical Center, Kurashiki, Okayama, Japan
b Department of Molecular Biology, Institute of Cellular and Molecular Biology, Okayama University Medical School, Okayama, Japan
c School of Biochemistry, University of Birmingham, Edgbaston, 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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