title: Oxidative damage to RNA and expression patterns of MTH1 in the hippocampi of senescence-accelerated SAMP8 mice and Alzheimer's disease patients.
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.
authors.affiliation: 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.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Song
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Zhang
authors.forename: Dong-Ge
authors.initials: DG
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Jun-De
authors.initials: JD
authors.lastname: Zheng
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Dai
authors.forename: Ai-Lian
authors.initials: AL
authors.lastname: Hei
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D011897:Random Allocation
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D012313:RNA; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; C509779:Nudt1 protein, mouse; D045643:DNA Repair Enzymes