Age-related alterations in the expression of MTH2 in the hippocampus of the SAMP8 mouse with learning and memory deterioration.
MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis in the nucleotide pool, thereby preventing DNA replication errors. MTH2 (Mut T homolog 2), which belongs to this family of proteins, possesses 8-oxo-7,8-dihydro-2'-deoxyguanosine triphosphatase (8-oxo-dGTPase) activity and appears to function in the protection of the genetic material from the untoward effects of endogenous oxygen radicals. To examine the roles of MTH2 in the aging process, we used the senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes and declining abilities of learning and memory. Immunohistochemical and western blot analysis revealed that the level of MTH2 protein in the hippocampus of the SAMP8 mouse progressively decreases beginning from four months after birth, whereas no such change was observed in the control senescence-accelerated resistant mouse 1 (SAMR1). Under these conditions, 8-oxoguanine accumulates in the nuclear DNA in the CA1 and CA3 subregions of the hippocampus of SAMP8 in an age-dependent manner. In SAMR1 mice, accumulation of 8-oxoguanine in the DNA was not observed. These results suggest that the MTH2 deficiency might be one of the causative factors for accelerated aging.
Zheng
Jun-De
JD
The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Dong Dan, Beijing 100730, PR China.
Hei
Ai-Lian
AL
Zuo
Ping-Ping
PP
Dong
Yi-Long
YL
Song
Xiao-Ning
XN
Takagi
Yasumitsu
Y
Sekiguchi
Mutsuo
M
Cai
Jian-Ping
JP
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005609:Free Radicals / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008818:Mice, Neurologic Mutants; D018384:Oxidative Stress / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D005609:Free Radicals; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C475692:Nudt15 protein, mouse