Neurochemical Research

, Volume 36, Issue 8, pp 1558–1565

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

  • Xiao-Ning Song
  • Li-Qun Zhang
  • Dong-Ge Liu
  • Jing Lin
  • Jun-De Zheng
  • Da-Peng Dai
  • Ai-Lian Hei
  • Hiroshi Hayakawa
  • Mutsuo Sekiguchi
  • Jian-Ping Cai
Original Paper

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.

Keywords

Senescence-accelerated mouse Alzheimer’s disease Oxidative damage MTH1 8-Oxoguanine 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Xiao-Ning Song
    • 1
  • Li-Qun Zhang
    • 2
  • Dong-Ge Liu
    • 1
    • 3
  • Jing Lin
    • 1
  • Jun-De Zheng
    • 1
  • Da-Peng Dai
    • 1
  • Ai-Lian Hei
    • 1
  • Hiroshi Hayakawa
    • 4
  • Mutsuo Sekiguchi
    • 4
  • Jian-Ping Cai
    • 1
  1. 1.The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of HealthBeijingPeople’s Republic of China
  2. 2.Graduate School, Peking Union Medical CollegeChinese Academy of Medical SciencesBeijingPeople’s Republic of China
  3. 3.Department of Pathology, Beijing HospitalMinistry of HealthBeijingPeople’s Republic of China
  4. 4.Frontier Research CenterFukuoka Dental CollegeFukuokaJapan

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