Peroxynitrite inactivates prostacyclin synthase by heme-thiolate-catalyzed tyrosine nitration

Zou M., Yesilkaya A., Ullrich V.

DRUG METABOLISM REVIEWS, vol.31, no.2, pp.343-349, 1999 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31 Issue: 2
  • Publication Date: 1999
  • Doi Number: 10.1081/dmr-100101922
  • Journal Name: DRUG METABOLISM REVIEWS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.343-349
  • Keywords: superoxide, nitric oxide, cytochrome P450, endothelial cell, NITRIC-OXIDE SYNTHASE, SUPEROXIDE, INHIBITION, MECHANISM, CELLS
  • Akdeniz University Affiliated: Yes

Abstract

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 mu M peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.