ADP-ribosyl pyrophosphatases (ADPRase) has been known to catalyze the hydrolysis of ADP-ribose to ribose-5-phosphate and AMP. The role of ADPRase has been suggested to sanitize the cell by removing potentially toxic ADP-ribose. In this study, we examined the effect of nitric oxide on ADPRase activity in macrophages.

ADPRase activity was measured in NO-inducing J774 cells. For in vitro experiments, recombinant human ADPRase was prepared in bacteria.

ADPRase activity was increased by the treatment of exogenous NO generating reagent, sodium nitroprusside (SNP), in J774 cells. The increased ADPRase activity was mediated by the post-translational modification, likely to cause cADP-ribosylation via nitrosylation of cysteine residue on the enzyme. The stimulation with endogeneous NO inducers, TNF-α/IFN-γ, also increased ADPRase activity through NO synthesis. Futhermore, ADPRase activity may be mediated by the post-translational modification of ADPRase, ADP-ribosylation.

These results indicate that NO synthesized by macrophage activation plays a critical role in the increase in ADPRase activity following ADP-ribose metabolism.