Lin L H, Cao S, Yu L, Cui J, Hamilton W J, Liu P K
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurochem. 2000 Mar;74(3):1098-105. doi: 10.1046/j.1471-4159.2000.741098.x.
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 (FblR) or sham operations. We found that the OGG activity in nuclear extracts, under the condition in which other nucleases did not destroy the oligodeoxynucleotide duplex, excised oh8dG with the greatest efficiency on the oligodeoxynucleotide duplex containing oh8dG/dC and with less efficiency on the heteroduplex containing oh8dG/dT, oh8dG/dG, or oh8dG/dA. This specificity was the same as for the recombinant type 1 OGG (OGG1) of humans. We observed that the OGG1 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 FblR-induced DNA lesions in an indicator gene (the c-fos gene) 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 functional role in reducing oxidative gene damage in the brain after FblR.
修复酶8-氧代鸟嘌呤糖基化酶/无嘧啶/无嘌呤裂解酶（OGG）可去除人类细胞中的8-羟基-2'-脱氧鸟苷（oh8dG）。我们的目标是检测经前脑缺血再灌注（FblR）或假手术处理的雄性C57BL/6小鼠脑细胞核中的oh8dG去除活性。我们发现，在其他核酸酶不破坏寡脱氧核苷酸双链体的条件下，核提取物中的OGG活性对含有oh8dG/dC的寡脱氧核苷酸双链体切除oh8dG的效率最高，而对含有oh8dG/dT、oh8dG/dG或oh8dG/dA的异源双链体切除效率较低。这种特异性与人类重组1型OGG（OGG1）相同。我们观察到，缺血90分钟和再灌注20 - 30分钟后，小鼠脑中OGG1肽及其活性显著增加。脑OGG1蛋白水平和活性的增加与FblR诱导的脑指示基因（c-fos基因）中DNA损伤的升高呈正相关。数据表明，OGG1蛋白可能在小鼠脑中切除oh8dG，并且OGG1的活性可能在减少FblR后脑氧化基因损伤中发挥功能作用。
