Inhibition of peroxynitrite-mediated tyrosine nitration by a novel pyrrolopyrimidine antioxidant.
Inhibition of peroxynitrite-mediated tyrosine nitration by a novel pyrrolopyrimidine antioxidant.
复制标题
新型吡咯并嘧啶抗氧化剂抑制过氧亚硝酸盐介导的酪氨酸硝化。
DOI：
10.1016/s0014-2999(98)00399-9
复制
发表时间：
1998
影响因子：
5
通讯作者：
Quinn,MT
中科院分区：
文献类型：
--
作者：
Rohn,TT;Quinn,MT
过氧亚硝酸盐是一种细胞毒性的自由基物种，由超氧化物和一氧化氮结合而成。本研究的目的是检测新型抗氧化剂U-101033E防止过氧亚硝酸根介导的红细胞膜蛋白氧化损伤的能力。过氧亚硝酸盐处理红细胞膜会导致氧化损伤，膜蛋白的交联和酪氨酸残基的硝化都是证据。膜蛋白的交联是巯基氧化的结果，二硫苏糖醇的加入可完全阻断膜蛋白的交联。二硫苏糖醇还可以阻止过氧亚硝酸根介导的酪氨酸红细胞蛋白硝化。U-101033E以浓度依赖的方式抑制过氧亚硝酸根处理的红细胞膜蛋白中硝基酪氨酸的形成，在100μ的MU-101033E时保护作用最强。然而，在类似的U-101033E阻止酪氨酸硝化的浓度下，它对膜蛋白的交联作用很小或没有影响。我们的结果表明，U-101033E可能截留了一种过氧亚硝酸根衍生的活性氮物种，该物种能够硝化酪氨酸残基。U-101033E阻止过亚硝酸根硝化酪氨酸的能力代表了这类抗氧化剂的新作用，并表明吡咯嘧啶类化合物可能在治疗过氧亚硝酸根介导的损伤相关疾病中有用。
Peroxynitrite is a cytotoxic, free radical species that is formed by the combination of superoxide and nitric oxide. The goal of the present study was to examine the ability of a novel antioxidant, U-101033E, to prevent peroxynitrite-mediated oxidative damage of red blood cell membrane proteins. Treatment of red blood cell membranes with peroxynitrite resulted in oxidative damage as evidenced by the presence of both membrane protein cross-linking and nitration of tyrosine residues. Membrane protein cross-linking was the result of oxidation of sulfhydryl groups and was completely blocked by the addition of dithiothreitol. Dithiothreitol also prevented peroxynitrite-mediated nitration of tyrosine red blood cell proteins. U-101033E prevented nitrotyrosine formation in peroxynitrite-treated red blood cell membrane proteins in a concentration-dependent manner, with maximal protection observed at 100 μM U-101033E. However, at a similar concentration where U-101033E prevented tyrosine nitration, it had little or no effect on membrane protein cross-linking. Our results suggest that U-101033E may be intercepting a peroxynitrite-derived reactive nitrogen species that is capable of nitrating tyrosine residues. The ability of U-101033E to prevent tyrosine nitration by peroxynitrite represents a new role for this class of antioxidants and suggests that the pyrrolopyrimidines may be useful in the treatment of diseases where peroxynitrite-mediated injury is implicated.