Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues.

Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues.
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不同大鼠组织 DNA 和 RNA 中 8-氧代鸟嘌呤的年龄依赖性积累。

DOI:
10.1155/2013/303181
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发表时间:
2013
影响因子:
--
通讯作者:
Cai JP
Cai JP
中科院分区:
生物学2区
文献类型:
--
作者:
Nie B;Gan W;Shi F;Hu GX;Chen LG;Hayakawa H;Sekiguchi M;Cai JP

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通过分析来自自然衰老的Sprague-Dawley(SD)大鼠的各种组织标本的核酸,研究了核酸的氧化损伤与动物衰老之间的关系。为此,我们建立了一种准确、灵敏的同位素稀释LC-MS/MS方法,用于DNA和RNA中8-oxo-7,8-dihydroguanosine(8-oxo-Gsn)的检测。在检查的各种器官中观察到氧化DNA和RNA损伤的年龄依赖性增加,包括脑、肝、肾和睾丸。在海马、大脑皮层和小脑这三个脑部位中观察到8-oxo-dGsn和8-oxo-Gsn含量的类似增加,其中海马的值总是最高。当用尿液定量氧化的鸟苷代谢物时,观察到8-氧代-dGsn和8-氧代-Gsn的类似年龄依赖性增加。然而,与来自组织的核酸样品的结果不同,8-oxo-Gsn的量显著高于8-oxo-dGsn的量,这可能反映了RNA降解比DNA降解更频繁地发生的事实。我们的发现表明,尿中8-oxo-Gsn的量可以被认为是敏感测量氧化应激和衰老的生物标志物。
The relationship between the oxidative damage of nucleic acids and aging of animals was investigated by analyzing the nucleic acids derived from various tissue specimens of naturally aged Sprague-Dawley (SD) rats. For this purpose, we established an accurate and sensitive isotope-diluted LC-MS/MS method to determine the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn) in DNA and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in RNA. An age-dependent increase in oxidative DNA and RNA damage was observed in the various organs examined, including the brain, liver, kidneys, and testes. Similar increases in the 8-oxo-dGsn and 8-oxo-Gsn contents were observed in three parts of the brain, the hippocampus, cerebral cortex, and cerebellum, among which, the values for the hippocampus were always the highest. When the oxidized guanosine metabolites were quantified with urine, a similar age-dependent increase was observed for both 8-oxo-dGsn and 8-oxo-Gsn. However, unlike the results of nucleic acid samples derived from the tissues, the amount of 8-oxo-Gsn was significantly higher compared to that of 8-oxo-dGsn, probably reflecting the fact that RNA degradation occurs more frequently than DNA degradation. Our finding indicates that the amount of urinary 8-oxo-Gsn could be considered as a biomarker for the sensitive measurement of oxidative stress and aging.
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