The role of caspases in different paradigms of NO-triggered cell death
CGC were exposed to increasing concentrations of NO donors with different release kinetics or to ONOO− for 4 hr. Protection by z-D-cbk was examined. The concentrations of S-nitrosocysteine (SNOC), a fast release donor (t1/2 < 10 min), or ONOO− were those at which maximum protection was observed. For the donors with intermediate release kinetics (t1/2 = 10−120 min), DEA-NONOate (D/NO) and spermine-NONOate (S/NO), the highest concentrations are shown, at which >80% protection was observed. For the slow-release (t1/2 > 2 hr) donors GSNO and SNAP, the highest concentrations are shown, at which complete protection was observed. For the latter group of donors the concentrations at which no protection was observed are also indicated. Notably, toxicity by all donors, at all concentrations shown, was completely prevented by 2 µM MK801. Apoptosis was determined by counting triplicate samples after staining of chromatin with H-3 3 342 and all data were confirmed by MTT measurements, 12 hr after addition of the stimulus.