Inhibition of peroxynitrite-induced dityrosine formation with oxidized and reduced thiols, nitric oxide donors, and purine derivatives

Antioxid Redox Signal. 2001 Feb;3(1):165-71. doi: 10.1089/152308601750100704.

Abstract

Peroxynitrite, formed by the combination of superoxide anion and nitric oxide, is a powerful oxidant at physiological pH and is apparently involved in the pathogenesis of several human diseases. Therefore, inhibitors of peroxynitrite-induced oxidation are important targets for pharmaceutical development. The reaction of peroxynitrite with L-tyrosine, one of its biological targets, yields stable products, including nitrotyrosine and dityrosine. Here we test the ability of thiols, nitric oxide donors, and purine derivatives to inhibit peroxynitrite-induced dityrosine formation in a physiological buffer containing bicarbonate/CO2. We show that both reduced and oxidized thiols, nitric oxide donors, and urate, but not other purine derivatives, reduce peroxynitrite-induced dityrosine formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Structure
  • Nitrates / antagonists & inhibitors*
  • Nitrates / pharmacology
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Donors / pharmacology*
  • Oxidative Stress
  • Purines / pharmacology*
  • Sulfhydryl Compounds / pharmacology*
  • Tyrosine / analogs & derivatives
  • Tyrosine / antagonists & inhibitors
  • Tyrosine / metabolism*
  • Uric Acid / pharmacology*
  • Uric Acid / therapeutic use

Substances

  • Nitrates
  • Nitric Oxide Donors
  • Purines
  • Sulfhydryl Compounds
  • peroxynitric acid
  • Uric Acid
  • Nitric Oxide
  • Tyrosine
  • dityrosine