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Oxidative Damage to RNA and Expression Patterns of MTH1 in the Hippocampi of Senescence-Accelerated SAMP8 Mice and Alzheimer’s Disease Patients

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Abstract

Mammalian MTH1 protein, a MutT-related protein, catalyzes the hydrolysis of 8-oxo-7,8-dihydroguanosine triphosphate (8-oxoGTP) to monophosphate, thereby preventing incorporation of 8-oxo-7,8-dihydroguanine (8-oxoguanine) into RNA. In this study, we applied immunohistochemistry to follow the expression of MTH1 and the amount of 8-oxoguanine in RNA during aging. There were increased amounts of 8-oxoguanine in RNA in the CAl and CA3 subregions of hippocampi of 8- and 12-month-old SAMP8 mice, which exhibited early aging syndromes and declining learning and memory abilities compared to those of age-matched control SAMR1 mice. The expression levels of MTH1 in the hippocampi of 8- and 12-month-old SAMP8 mice were significantly lower than those of control mice. Therefore, in this mouse model, age-related accumulation of 8-oxoguanine in RNA is correlated with decreased expression of MTH1. Increased amounts of 8-oxoguanine in the RNA, and decreased expression of MTH1 were also observed in the hippocampi of patients suffering from Alzheimer’s disease. These results suggest that MTH1 deficiency might be a causative factor for aging and age-related disorders.

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Acknowledgments

This work was supported by the Key International Science and Technology Cooperation Projects (2006DFB31410). We also thank the members of the Institute of Geriatrics of the Ministry of Health for their valuable advice and assistance.

Conflict of interest

There is no conflict of interest.

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Authors and Affiliations

  1. The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of Geriatrics, Ministry of Health, No. 1, DaHua Road, Dong Dan, 100730, Beijing, People’s Republic of China

    Xiao-Ning Song, Dong-Ge Liu, Jing Lin, Jun-De Zheng, Da-Peng Dai, Ai-Lian Hei & Jian-Ping Cai

  2. Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, 100730, Beijing, People’s Republic of China

    Li-Qun Zhang

  3. Department of Pathology, Beijing Hospital, Ministry of Health, 100730, Beijing, People’s Republic of China

    Dong-Ge Liu

  4. Frontier Research Center, Fukuoka Dental College, Fukuoka, 814-0193, Japan

    Hiroshi Hayakawa & Mutsuo Sekiguchi

Authors
  1. Xiao-Ning Song
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  2. Li-Qun Zhang
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  3. Dong-Ge Liu
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  4. Jing Lin
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  5. Jun-De Zheng
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  6. Da-Peng Dai
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  7. Ai-Lian Hei
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  8. Hiroshi Hayakawa
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  9. Mutsuo Sekiguchi
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  10. Jian-Ping Cai
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Corresponding author

Correspondence to Jian-Ping Cai.

Additional information

The authors Xiao-Ning Song and Li-Qun Zhang contributed equally to this work.

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Song, XN., Zhang, LQ., Liu, DG. et al. Oxidative Damage to RNA and Expression Patterns of MTH1 in the Hippocampi of Senescence-Accelerated SAMP8 Mice and Alzheimer’s Disease Patients. Neurochem Res 36, 1558–1565 (2011). https://doi.org/10.1007/s11064-011-0484-4

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  • DOI: https://doi.org/10.1007/s11064-011-0484-4

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