Inhibitors of poly(ADP-ribose) polymerase block nitric oxide-induced apoptosis but not differentiation in human leukemia HL-60 cells.

ABSTRACT

Previous studies have shown that chemically generated nitric oxide (NO) can induce human leukemia HL-60 cells to undergo monocytic differentiation. We show here that exposure of HL-60 cells to chemical NO generators induces cell death via apoptosis which was examined by morphological and biochemical criteria. The activation of poly(ADP-ribose) polymerase (pADPRp) was found to occur during the process of cell death. The NO-induced apoptosis of HL-60 cells was effectively prevented by the ADP-ribosylation inhibitors nicotinamide (NA) and 3-aminobenzamide (3-AB). Since NO not only induced apoptosis but also triggered differentiation under the same concentration, we thus examined whether pADPRp participated in monocytic differentiation. It is of interest to note that the NO-mediated monocytic differentiation was not affected by 3-AB or NA. These findings indicate that activation of pADPRp is specifically involved in NO-induced apoptosis but not differentiation.