Interference of 7,8-dihydroneopterin with peroxynitrite-mediated reactions.

Oettl K, Greilberger J, Dikalov S, Reibnegger G
Biochem Biophys Res Commun. 2004 321 (2): 379-85

PMID: 15358187 · DOI:10.1016/j.bbrc.2004.06.157

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.

MeSH Terms (13)

Electron Spin Resonance Spectroscopy Free Radical Scavengers Hydroxylation Luminescent Measurements Molsidomine Neopterin Oxidation-Reduction Peroxynitrous Acid Piperidines Salicylic Acid Spectrometry, Fluorescence Superoxides Tyrosine

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