Age-associated decrease of oxidative repair enzymes, human 8-oxoguanine DNA glycosylases (hOgg1), in human aging.
8-Oxoguanine has been shown to be a dominant cause of oxidative DNA damage by oxygen free radicals in eukaryotic cells. The 8-oxoguanine repair-specific enzyme 8-oxoguanine-DNA glycosylase (hOgg1) was recently cloned and was observed to conduct mainly short-patch base-excision repair. It has also been suggested that reactive oxygen species play an important role in the cellular aging process. We explored the association between the hOgg1 enzyme activity in somatic cells of human subjects of various ages and the role of hOgg1(326) genetic polymorphism. An 8-oxoguanine-containing 28 mer oligonucleotide was end-labeled with gamma-32P ATP and incubated with protein extracts from peripheral blood lymphocytes (PBL) from 78 healthy individuals ranging in age from newborn to 91 years old. The hOgg1 repair activity toward the radiolabelled 8-oxoguanine-containing DNA was determined, and the results indicated a significant age-dependent decrease in the hOgg1 activity in their lymphocytes. Significantly reduced activity was also shown in those with Cysteine/Cysteine genotypes. The genders of the subjects were not shown to be associated. These results provide an important observation regarding the cellular hOgg1 activity in somatic cells during the normal human aging processes.
Chen
Shin-Kuang
SK
Institute of Environmental Health Sciences, National Yangming University, Taiwan.
Hsieh
Wanhua Annie
WA
Tsai
Mong-Hsun
MH
Chen
Chien-Chih
CC
Hong
Antonio Ic
AI
Wei
Yau-Huei
YH
Chang
Wushou P
WP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D043382:DNA-Formamidopyrimidine Glycosylase; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000502:physiology
D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase