Age-Dependent Accumulation of 8-Oxoguanine in the DNA and RNA in Various Rat Tissues

  • Ben Nie
    Graduate School, Wenzhou Medical College, University Town, Wenzhou, Zhejiang 325035, China
  • Wei Gan
    The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Beijing 100730, China
  • Fei Shi
    The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Beijing 100730, China
  • Guo-Xin Hu
    Graduate School, Wenzhou Medical College, University Town, Wenzhou, Zhejiang 325035, China
  • Lian-Guo Chen
    Graduate School, Wenzhou Medical College, University Town, Wenzhou, Zhejiang 325035, China
  • Hiroshi Hayakawa
    Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan
  • Mutsuo Sekiguchi
    Frontier Research Center, Fukuoka Dental College, Fukuoka 814-0193, Japan
  • Jian-Ping Cai
    The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, No. 1 Dahua Road, Dongdan, Beijing 100730, China

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<jats:p>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-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msup><mml:mn>2</mml:mn><mml:mo>′</mml:mo></mml:msup></mml:mrow></mml:math>-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.</jats:p>

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