Peroxynitrite induces apoptosis of HL-60 cells by activation of a caspase-3 family protease |
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Authors: | Lin, King-Teh Xue, Ji-Yan Lin, Marie C. Spokas, Eric G. Sun, Frank F. Wong, Patrick Y.-K. |
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Abstract: | Apoptosis is an active process critical for the homeostasis oforganisms. Enzymes of the caspase family are responsible for executingthis process. We have previously shown that peroxynitrite (ONOO), a biologicalproduct generated from the interaction of nitric oxide and superoxide,induces apoptosis of HL-60 cells. The aim of this study was toelucidate the mechanisms involved in the execution process ofperoxynitrite-induced apoptosis. Proteolytic cleavage ofpoly(ADP-ribose) polymerase, an indication of caspase-3 family proteaseactivation and an early biochemical event accompanying apoptosis, wasobserved in a time-dependent manner during peroxynitrite-induced apoptosis of HL-60 cells. Activation of caspase-3 duringperoxynitrite-induced apoptosis was substantiated by monitoringproteolysis of the caspase-3 proenzyme and by measuring caspase-3activity with a fluorogenic substrate. Furthermore, pretreatment ofHL-60 cells withN-acetyl-Asp-Glu-Val-Asp-aldehyde, aspecific inhibitor of caspase-3, but notN-acetyl-Tyr-Val-Ala-Asp-aldehyde, aspecific inhibitor of caspase-1, decreased peroxynitrite-induced apoptosis. These results suggest that the activation of a caspase-3 family protease is essential for initiating the execution process ofperoxynitrite-induced apoptosis of HL-60 cells. |
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