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

Authors

  • Xiao-Ning Song
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
  • Li-Qun Zhang
    • Graduate School, Peking Union Medical CollegeChinese Academy of Medical Sciences
  • Dong-Ge Liu
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
    • Department of Pathology, Beijing HospitalMinistry of Health
  • Jing Lin
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
  • Jun-De Zheng
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
  • Da-Peng Dai
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
  • Ai-Lian Hei
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
  • Hiroshi Hayakawa
    • Frontier Research CenterFukuoka Dental College
  • Mutsuo Sekiguchi
    • Frontier Research CenterFukuoka Dental College
    • The Key Laboratory of Geriatrics, Beijing Hospital, Beijing Institute of GeriatricsMinistry of Health
Original Paper

DOI: 10.1007/s11064-011-0484-4

Cite this article as:
Song, X., Zhang, L., Liu, D. et al. Neurochem Res (2011) 36: 1558. doi:10.1007/s11064-011-0484-4

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 mouseAlzheimer’s diseaseOxidative damageMTH18-Oxoguanine

Copyright information

© Springer Science+Business Media, LLC 2011