Strain-specific differences in the expression and activity of Ogg1 in the CNS.
The expression and activity of 8-oxoguanosine DNA-glycosylase (Ogg1), a key enzyme responsible forthe clearance of the oxidized DNA base 8-hydroxy-2'-deoxyguanosine (oxo8dG), was determined in the cerebellum (CB) and the caudate and the putamen (CP) of male Balb/c, ICR, and C57BL/J mice. There was no significant difference in the protein expression of Ogg1 in the CB or CP. The activity of Ogg1 was not significantly different in the CB; however, in the CP of ICR mice, the activity of Ogg1 was 34% and 31% lower than Balb/c and C57BL/J, respectively. In contrast, the levels of oxo8dG in the CB and CP of C57BL/J mice were nearly twice as high as the values in both regions of Balb/c and ICR mice. The activity of superoxide dismutases (SOD) appeared to account for the differences in the levels of oxo8dG in the C57BL/J strain. Total SOD in the C57BL/J strain was two- and fourfold higher in the CB and CP, respectively, versus the other strains. These results suggest that the enhanced vulnerability of the C57BL/J strain to neurotoxicants may not be due to a decreased capacity for DNA repair, but rather, the significantly higher activity of SODs, which may cause these pathways to become more readily saturated.
Mosquera
Diana I
DI
Department of Neurology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Stedeford
Todd
T
Cardozo-Pelaez
Fernando
F
Sanchez-Ramos
Juan
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004361:Drug Tolerance / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D009498:Neurotoxins / Q000494:pharmacology; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000378:metabolism
D009498:Neurotoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine