Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice
Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice
复制标题
DOI：
10.1097/00004647-199905000-00003
复制
发表时间：
1999-05-01
影响因子：
6.3
通讯作者：
Chan, PH
中科院分区：
文献类型：
--
作者：
Fujimura, M;Morita-Fujimura, Y;Chan, PH
作者检测了小鼠短暂性局灶性脑缺血前后DNA碱基切除修复途径中的多功能蛋白--脱嘌呤/脱嘧啶核酸内切酶(APE/Ref-1)的蛋白表达。免疫组织化学显示APE/Ref-1在对照组整个脑区均有核表达。缺血60分钟后，缺血中心区的核免疫反应最早下降5分钟，随后整个大脑中动脉区域的APE/Ref-1阳性细胞显著减少。对来自非缺血区大脑的样本进行蛋白质印迹分析，显示出一条37 kDa的特征性条带，该条带在缺血后有所减少。在缺血后24小时观察到明显的DNA片段化，而在4小时没有观察到明显的DNA断裂。作者的数据提供了第一个证据，表明APE/Ref-1在短暂性局灶性缺血后迅速下降，并且这种下降先于注定会出现坏死和凋亡的大脑区域的DNA片段化高峰。虽然APE/Ref-1的降低与缺血坏死和细胞凋亡的直接关系还需要进一步的研究，但我们的结果提示APE/Ref-1的迅速降低和DNA修复机制的失效可能参与了短暂性局灶性脑缺血后的坏死或凋亡。
The authors examined the protein expression of apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, before and after transient focal ischemia in mice. Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the entire region of the control brains. Nuclear immunoreactivity was decreased as early as 5 minutes after 60 minutes of ischemia in the ischemic core, which was followed by a significant reduction of APE/Ref-1-positive cells in the entire middle cerebral artery territory. Western blot analysis of the sample from the nonischemic brain showed a characteristic 37-kDa band, which was reduced after ischemia. A significant amount of DNA fragmentation was observed at 24 hours, but not at 4 hours, after ischemia. The authors' data provide the first evidence that APE/Ref-1 rapidly decreases after transient focal ischemia, and that this reduction precedes the peak of DNA fragmentation in the brain regions that are destined to show necrosis and apoptosis. Although further examination is necessary to elucidate the direct relationship between the APE/Ref-1 decrease and ischemic necrosis and apoptosis, our results suggest the possibility that rapid decrease of APE/Ref-1 and the failure of the DNA repair mechanism may contribute to necrosis or apoptosis after transient focal ischemia.