Peroxynitrite inactivates prostacyclin synthase by heme-thiolate-catalyzed tyrosine nitration.
Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable substrate analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 microM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
Zou
M
M
Faculty of Biology, University of Konstanz, Germany.
Yesilkaya
A
A
Ullrich
V
V
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol / Q000502:physiology; D006418:Heme / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
D065607:Cytochrome P-450 Enzyme Inhibitors; D009566:Nitrates; D013438:Sulfhydryl Compounds; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D014443:Tyrosine; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase