Peroxynitrite-induced apoptosis involves activation of multiple caspases in HL-60 cells

Shougang Zhuang, Gabriel Simon
2000 American Journal of Physiology - Cell Physiology  
Zhuang, Shougang, and Gabriel Simon. Peroxynitriteinduced apoptosis involves activation of multiple caspases in HL-60 cells. Am J Physiol Cell Physiol 279: C341-C351, 2000.-In this study, we show that caspases 2, 3, 6, and 7 were activated during peroxynitrite-induced apoptosis in human leukemia HL-60 cells and that processing of these caspases was accompanied by cleavage of poly(ADP-ribose) polymerase and lamin B. Treatment of cells with DEVDfluoromethyl ketone (FMK), a selective inhibitor for
more » ... ctive inhibitor for caspase 3-like proteases, resulted in a marked diminution of apoptotic cells. VAVAD-FMK, an inhibitor of caspase 2, partially inhibited the apoptotic response to peroxynitrite. However, selective inactivation of caspase 6 by VEID-FMK did not affect apoptosis rates. These data suggest that caspase 3-like proteases and caspase 2, but not caspase 6, are required for peroxynitrite-induced apoptosis in this cell type. Moreover, we demonstrate that peroxynitrite treatment stimulated activation of caspases 8 and 9, two initial caspases in the apoptotic signaling pathway, and preincubation of cells with their inhibitor, IETD-FMK, inhibited activation of caspase 3-like proteases and caspase 2 at the concentration that prevents the apoptosis. These observations, together, suggest that caspase 8 and/or caspase 9 mediates activation of caspase 3-like proteases and caspase 2 during the apoptosis induced by peroxynitrite in HL-60 cells. poly(adenosine 5Ј-diphosphate-ribose) polymerase; lamin B; caspase cysteine protease
doi:10.1152/ajpcell.2000.279.2.c341 pmid:10913000 fatcat:zgqwlvconra2nffkjxm7yvd7ha