Peroxynitrite mediated oxidation of purine bases of nucleosides and isolated DNA
Peroxynitrite mediated oxidation of purine bases of nucleosides and isolated DNA
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DOI：
10.3109/10715769609088035
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发表时间：
1996-01-01
影响因子：
3.3
通讯作者：
Cadet, J
中科院分区：
文献类型：
--
作者：
Douki, T;Cadet, J
一氧化氮与超氧阴离子反应产生高活性物质过氧亚硝酸盐 (ONOO-)。该化合物已被证明是脂质和蛋白质的强氧化剂。然而，除了诱导链断裂之外，没有关于其对 DNA 影响的数据。我们报告了过氧亚硝酸盐与核苷和分离 DNA 的腺嘌呤和鸟嘌呤部分反应的研究结果。分析样品中的 8-氧代-7,8-二氢-2'-脱氧鸟苷 (8-oxo-dGuo)、2,2-二氨基-4-[(2-脱氧-β-D-赤式-呋喃戊糖基)氨基]-5-(2H)-恶唑酮 (恶唑酮) 和 8-氧代-7,8-二氢-2'-脱氧腺苷(8-氧代-dAdo)。将过氧亚硝酸盐处理的效果与选择作为羟基自由基来源的充气水溶液中的电离辐射的效果进行了比较。在核苷水平上，两种氧化条件都会导致恶唑酮和 8-oxo-dAdo 的形成。此外，还提供了4-羟基-8-氧代-4,8-二氢-2'-脱氧鸟苷的4R*和4S*非对映异构体形成的证据。选择后者的 dGuo 氧化产物作为过亚硝酸与过氧化氢反应时释放单线态氧 (O-1(2)) 的标记。然后研究了分离的 DNA 中嘌呤碱基的氧化。在暴露于伽马辐射后，在双链 DNA 中观察到 8-oxo-dGuo、恶唑酮和 8-oxo-dAdo 的水平显着增加。过氧亚硝酸盐处理后形成恶唑酮和 8-oxo-dAdo，但未检测到 8-oxo-dGuo 的量显着增加。这些结果表明，过氧亚硝酸盐对核苷和分离的 DNA 中的嘌呤部分均表现出氧化特性。然而，与过亚硝酸盐处理相比，暴露于伽马辐射后观察到的 DNA 内氧化损伤分布的显着差异质疑羟基自由基作为过亚硝酸分解释放的主要氧化物质的参与。
Reaction of nitric oxide with superoxide anion produces the highly reactive species peroxynitrite (ONOO-). This compound has been shown to be a strong oxidant of lipids and proteins. However, no data are available on its effect on DNA, with the exception of the induction of strand breaks. We report the result of studies on the reactions of peroxynitrite with the adenine and guanine moieties of nucleosides and isolated DNA. The samples were analyzed for 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo), 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-5-(2H)-oxazolone (oxazolone) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dAdo). The effects of peroxynitrite treatment were compared with those of ionizing radiation in aerated aqueous solution, chosen as a source of hydroxyl radicals. At the nucleoside level, both oxidizing conditions led to the formation of oxazolone and 8-oxo-dAdo. In addition, evidence was provided for the formation of the 4R* and 4S* diastereoisomers of 4-hydroxy-8-oxo-4,8-dihydro-2'-deoxyguanosine. The latter dGuo oxidation products were chosen as markers of the release of singlet oxygen (O-1(2)) upon reaction of peroxynitrous acid with hydrogen peroxide. Oxidation of purine bases was then studied within isolated DNA. A significant increase in the level of 8-oxo-dGuo, oxazolone and 8-oxo-dAdo was observed within double stranded DNA upon exposure to gamma-radiation. Oxazolone and 8-oxo-dAdo were formed upon peroxynitrite treatment but no significant increase in the amount of 8-oxo-dGuo was detected. These results showed that peroxynitrite exhibits oxidizing properties toward purine moieties both in nucleosides and isolated DNA. However, the significant differences in the oxidative damage distribution within DNA observed after exposure to gamma radiation by comparison with peroxynitrite treatment questions the involvement of hydroxyl radicals as the main oxidizing species released by decomposition of peroxynitrous acid.