Dissociation of DNA fragmentation from other hallmarks of apoptosis in nitric oxide-treated neutrophils: differences between individual nitric oxide donor drugs.
The events of apoptotic cell death can be experimentally dissociated from each other in certain cell types. Here we demonstrate the ability of structurally diverse nitric oxide (NO) donating compounds to delay or enhance neutrophil apoptosis and to differentially influence distinct parameters of programmed cell death. We provide evidence that high concentrations of the NO donors GEA 3162, SPER/NO, and DEA/NO induce morphological and biochemical markers of neutrophil apoptosis, but that only DEA/NO causes a concomitant increase in DNA fragmentation as evidenced by nuclear propidium iodide intercalation and the classical laddering pattern of electrophoresed DNA. In contrast, both GEA 3162 and SPER/NO inhibit DNA cleavage in a time- and concentration-dependent manner. We are the first to show that DNA fragmentation can be dissociated from other changes of apoptosis in NO-treated neutrophils and that it may therefore be inappropriate to assess NO-induced apoptosis solely by measuring DNA fragmentation in this cell type.
Taylor
E L
EL
Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH8 9AG, United Kingdom.
Megson
I L
IL
Haslett
C
C
Rossi
A G
AG
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007364:Intercalating Agents; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009589:Nitrogen Oxides; D011419:Propidium; D017452:Receptors, IgG / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D017304:Annexin A5; D006834:Hydrazines; D007364:Intercalating Agents; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D017452:Receptors, IgG; D014230:Triazoles; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D011419:Propidium; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C082874:GEA 3162