DNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts.
8-oxo-deoxyguanosine (8-oxodG) is one of the major DNA lesions formed upon oxidative attack of DNA. It is a mutagenic adduct that has been associated with pathological states such as cancer and aging. Base excision repair (BER) is the main pathway for the repair of 8-oxodG. There is a great deal of interest in the question about age-associated accumulation of this DNA lesion and its intracellular distribution, particularly with respect to mitochondrial or nuclear localization. We have previously shown that 8-oxodG-incision activity increases with age in rat mitochondria obtained from both liver and heart. In this study, we have investigated the age-associated changes in DNA repair activities in both mitochondrial and nuclear extracts obtained from mouse liver. We observed that 8-oxodG incision activity of mitochondrial extracts increases significantly with age, from 13.4 + or - 2.2 fmoles of oligomer/100 microg of protein/16 h at 6 to 18.6 + or - 4.9 at 14 and 23.7 + or - 3.8 at 23 months of age. In contrast, the nuclear 8-oxodG incision activity showed no significant change with age, and in fact slightly decreased from 11.8 + or - 3 fmoles/50 microg of protein/2 h at 6 months to 9.7 + or - 0.8 at 14 months. Uracil DNA glycosylase and endonuclease G activities did not change with age in nucleus or mitochondria. Our results show that the repair of 8-oxodG is regulated differently in nucleus and mitochondria during the aging process. The specific increase in 8-oxodG-incision activity in mitochondria, rather than a general up-regulation of DNA metabolizing enzymes in those organelles, suggests that this pathway may be up regulated during aging in mice.
de Souza-Pinto
N C
NC
Laboratory of Molecular Genetics, NIA, National Institutes of Health, Baltimore, MD 21224, USA.
Hogue
B A
BA
Bohr
V A
VA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002457:Cell Extracts; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D045647:DNA Glycosylases; D004260:DNA Repair; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase
D002457:Cell Extracts; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002950:Citrate (si)-Synthase; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D003849:Deoxyguanosine