Up-regulation of base excision repair activity for 8-hydroxy-2 '-deoxyguanosine in the mouse brain after forebrain ischemia-reperfusion

The repair enzyme 8-oxoguanine glycosylase/apyrimidinic/apurinic lyase (OGG ) removes 8-hydroxy-2'-deoxyguanosine (oh8dG) in human cells. Our goal was to examine oh8dG-removing activity in the cell nuclei of male C57BL/6 mouse brains treated with either forebrain ischemia-reperfusion (FbIR) or sham o perations. We found that the OGG activity in nuclear extracts, under the co ndition in which other nucleases did not destroy the oligodeoxynucleotide d uplex, excised oh8dG with the greatest efficiency on the oligodeoxynucleoti de duplex containing oh8dG/dC and with less efficiency on the heteroduplex containing oh8dG/dT, oh8dG/dG, or oh8dG/dA. This specificity was the same a s for the recombinant type I OGG (OGG1) of humans. We observed that the OGG 1 peptide and its activity in the mouse brain were significantly increased after 90 min of ischemia and 20-30 min of reperfusion. The increase in the protein level and in the activity of brain OGG1 correlated positively with the elevation of FbIR-induced DNA lesions in an indicator gene (the c-fos g ene) of the brain. The data suggest a possibility that the OGG1 protein may excise oh8dG in the mouse brain and that the activity of OGG1 may have a f unctional role in reducing oxidative gene damage in the brain after FbIR.