Age-dependent down-regulation of mitochondrial 8-oxoguanine DNA glycosylase in SAM-P/8 mouse brain and its effect on brain aging.
Mitochondrial DNA (mtDNA) damage has been hypothesized to be responsible for aging and various neurological diseases. Abnormalities in 8-oxoguanine DNA glycosylase (OGG1) function can promote DNA oxidative damage, especially in the mitochondria. Here we report changes in the expression of OGG1 targeting to the nucleus, cytosol, and mitochondria in both accelerated senescence mice (SAM-P/8) and normal counterpart SAM-R/1 mice during brain aging. Our results showed that mRNA and protein levels of OGG1, especially OGG1 targeting to mitochondria, and the expression level of cytochrome c oxidase subunit III (COX III) in the brain of both SAM-P/8 mice and SAM-R/1 mice, decreased with age. However, such an age-dependent decrease in SAM-P/8 mice was larger than that in normal SAM-R/1 mice. These findings support the concept that down-regulation of OGG1, especially mitochondrial OGG1(mtOGG1) in SAM-P/8 mice, may promote brain aging by its effect on imbalance in the mtDNA damage repair systems, which leads to accumulation of mtDNA damage and oxidative phosphorylation-related protein dysfunction. Overall, our results provide novel insight into underlying the molecular mechanisms during brain aging.
Tian
Feng
F
Department of Biochemistry & Molecular Biology, Peking University Health Science Center, Peking University Research Center on Aging, Beijing, China.
Tong
Tan-Jun
TJ
Zhang
Zong-Yu
ZY
McNutt
Michael A
MA
Liu
Xin-Wen
XW
D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D045647:DNA Glycosylases / Q000096:biosynthesis*; D004272:DNA, Mitochondrial / Q000378:metabolism; D015536:Down-Regulation; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D010100:Oxygen