Inhibition of peroxynitrite-induced dityrosine formation with oxidized and reduced thiols, nitric oxide donors, and purine derivatives.
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.
Ferdinandy
P
P
Department of Biochemistry, Cardiovascular Research Group, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary.
Schulz
R
R
D015394:Molecular Structure; D009566:Nitrates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D018384:Oxidative Stress; D011687:Purines / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014527:Uric Acid / Q000494:pharmacology* / Q000627:therapeutic use
D009566:Nitrates; D020030:Nitric Oxide Donors; D011687:Purines; D013438:Sulfhydryl Compounds; C039642:peroxynitric acid; D014527:Uric Acid; D009569:Nitric Oxide; D014443:Tyrosine; C007543:dityrosine