Widner B, Baier-Bitterlich G, Wede I, Wirleitner B, Fuchs D
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Ludwig Boltzmann Institute for AIDS Research, Fritz Pregl Strasse 3, Innsbruck, A-6020, Austria.
Biochem Biophys Res Commun. 1998 Jul 20;248(2):341-6. doi: 10.1006/bbrc.1998.8856.
The impact of neopterin and 7,8-dihydroneopterin on peroxynitrite-induced nitration of l-tyrosine was studied. Neopterin derivatives and peroxynitrite are formed during immune response. Tyrosine nitration represents one major effect of nitric oxide-mediated cytotoxicity. Peroxynitrite formed in situ was co-incubated with tyrosine and neopterin or 7,8-dihydroneopterin or other pteridine derivatives, respectively. The nitration product, 3-nitro-l-tyrosine, was measured by HPLC via UV absorption at 360 nm. Neopterin (200 microM) increased the nitration rate between pH 4.0 and 5.5 up to +60%. 7,8-Dihydroneopterin inhibited tyrosine nitration over the whole pH range examined. In a series of various pteridine derivatives, neopterin and 7,8-dihydroneopterin achieved the strongest modulating effects on tyrosine nitration. Interactions of peroxynitrite with hydroxypropyl side chains of fully aromatic pterin derivatives may increase nitration, while partially hydrated pyrazino ring structures abate the reactivity of peroxynitrite. The results of this study suggest a potential impact of neopterin derivatives on peroxynitrite-mediated cytotoxicity.
研究了新蝶呤和7,8 - 二氢新蝶呤对过氧亚硝酸根诱导的L - 酪氨酸硝化作用的影响。新蝶呤衍生物和过氧亚硝酸根在免疫反应过程中形成。酪氨酸硝化是一氧化氮介导的细胞毒性的一种主要作用。将原位生成的过氧亚硝酸根分别与酪氨酸和新蝶呤或7,8 - 二氢新蝶呤或其他蝶啶衍生物共同孵育。通过在360nm处的紫外吸收，用高效液相色谱法测定硝化产物3 - 硝基 - L - 酪氨酸。新蝶呤（200μM）在pH 4.0至5.5范围内使硝化速率提高了60%。7,8 - 二氢新蝶呤在整个检测的pH范围内抑制酪氨酸硝化。在一系列不同的蝶啶衍生物中，新蝶呤和7,8 - 二氢新蝶呤对酪氨酸硝化具有最强的调节作用。过氧亚硝酸根与全芳香蝶呤衍生物的羟丙基侧链的相互作用可能会增加硝化作用，而部分水合的吡嗪环结构会降低过氧亚硝酸根的反应活性。本研究结果表明新蝶呤衍生物对过氧亚硝酸根介导的细胞毒性具有潜在影响。
