Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury
Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury
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DOI：
10.1006/nbdi.2001.0396
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发表时间：
2001-06-01
影响因子：
6.1
通讯作者：
Chan, PH
中科院分区：
文献类型：
--
作者：
Lewén, A;Sugawara, T;Chan, PH
DNA修复酶脱嘌呤/脱嘧啶核酸内切酶（或氧化还原效应因子-1，APE/Ref-1）参与氧化DNA损伤后脱嘌呤/脱嘧啶位点的碱基切除修复。我们研究了APE/Ref-1的表达及其与严重创伤性脑损伤后氧化应激的关系，这些创伤性脑损伤是由正常小鼠和过表达或低表达铜锌超氧化物歧化酶（SOD 1 TG和SOD 1 KO）的小鼠的皮质撞击造成的。氧自由基介导的细胞损伤可视化与8-羟基鸟嘌呤免疫反应作为DNA氧化的标志物，和原位hydroethidine氧化作为超氧化物产生的标志物。创伤后，APE/Ref-1在同侧皮质和海马的表达减少，与细胞溶质超氧化物歧化酶的基因剂量水平相关。APE/Ref-1表达的降低先于DNA片段化。伤后4 h APE/Ref-1蛋白水平与伤后1周损伤体积之间也存在密切相关性。我们的数据表明，APE/Ref-1蛋白水平的降低与创伤性脑损伤后的氧化应激水平密切相关。我们认为APE/Ref-1免疫反应性是氧化性细胞损伤的敏感标志物。(C)北京：科学出版社.
The DNA repair enzyme, apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1), is involved in base excision repair of apurinic/apyrimidinic sites after oxidative DNA damage. We investigated the expression of APE/Ref-1 and its relationship to oxidative stress after severe traumatic brain injury produced by controlled cortical impact in normal mice, and in mice over- or underexpressing copper-zinc superoxide dismutase (SOD1TG and SOD1KO, respectively). Oxygen free radical-mediated cellular injury was visualized with 8-hydroxyguanine immunoreactivity as a marker for DNA oxidation, and in situ hydroethidine oxidation as a marker for superoxide production. After trauma there was a reduced expression of APE/Ref-1 in the ipsilateral cortex and hippocampus that correlated with the gene dosage levels of cytosolic superoxide dismutase. The decrease in APE/Ref-1 expression preceded DNA fragmentation. There was also a close correlation between APE/Ref-1 protein levels 4 h after trauma and the volume of the lesion 1 week after injury. Our data have demonstrated that reduction of APE/Ref-1 protein levels correlates closely with the level of oxidative stress after traumatic brain injury. We suggest that APE/Ref-1 immunoreactivity is a sensitive marker for oxidative cellular injury. (C) 2001 Academic Press.