Interference of 7,8-dihydroneopterin with peroxynitrite-mediated reactions.
By in vitro studies 7,8-dihydroneopterin, which is secreted by macrophages stimulated by interferon-gamma, was reported to be a radical scavenger as well as a prooxidative agent depending on the experimental settings. In this study, we investigated the interference of 7,8-dihydroneopterin with peroxynitrite mediated reactions by different analytical procedures. Luminol chemiluminescence and oxidation of the spin probe 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine induced by peroxynitrite were inhibited by 7,8-dihydroneopterin. On the other hand, we found that 7,8-dihydroneopterin very efficiently inhibits nitration of tyrosine by peroxynitrite. Hydroxylation, however, was rather enhanced than inhibited, suggesting that 7,8-dihydroneopterin reacts in quite different manner with the intermediates generated from peroxynitrite. We provide the first evidence that a pterin radical is formed from a dihydropterin using EPR spectroscopy and 2,2,4-trimethyl-2H-imidazole-1-oxide as a spin trap. We conclude that 7,8-dihydroneopterin while being a weak scavenger of superoxide acts as a very efficient inhibitor of tyrosine nitration induced by peroxynitrite.
Oettl
Karl
K
Institute for Physiological Chemistry, Medical University Graz, Harrachgasse 21/II, A-8010 Graz, Austria. karl.oettl@meduni-graz.at
Greilberger
Joachim
J
Dikalov
Sergey
S
Reibnegger
Gilbert
G
D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000378:metabolism; D006900:Hydroxylation; D008163:Luminescent Measurements; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019798:Neopterin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism*; D010880:Piperidines; D020156:Salicylic Acid / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D016166:Free Radical Scavengers; D010880:Piperidines; D013481:Superoxides; C000976:7,8-dihydroneopterin; D030421:Peroxynitrous Acid; C103674:1-hydroxy-2,2,6,6-tetramethyl-4-oxopiperidine; D014443:Tyrosine; C002385:linsidomine; D019798:Neopterin; D008981:Molsidomine; D020156:Salicylic Acid