Peroxynitrite inactivates prostacyclin synthase by heme-thiolate-catalyzedtyrosine nitration

Previous work has shown a sensitive inhibition of prostacyclin synthase act ivity by peroxynitrite as well as by superoxide in the presence of NO donor s. Neither superoxide nor NO alone nor decomposed peroxynitrite is effectiv e. The inhibition of activity was paralleled by a nitration of a tyrosine r esidue and both could be prevented by a stable substrate analog. The same I C50 value for peroxynitrite was also found for the cellular prostacyclin ac tivity in endothelial and kidney mesangial cells, indicating that the antio xidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine stainin g after treatment of the tissue with 1 mu M peroxynitrite. It can be specul ated that this pathway of enzyme nitration is of pathophysiological signifi cance.