Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice.
Partial loss of the DNA repair scaffolding protein, Xrcc1, results in increased brain damage and reduced recovery from ischemic stroke in mice.
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DNA修复脚手架蛋白的部分丢失XRCC1导致脑损伤增加并减少小鼠缺血性中风的恢复。
DOI：
10.1016/j.neurobiolaging.2015.04.004
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发表时间：
2015-07
影响因子：
4.2
通讯作者：
Bohr VA
中科院分区：
文献类型：
--
作者：
Ghosh S;Canugovi C;Yoon JS;Wilson DM 3rd;Croteau DL;Mattson MP;Bohr VA
DNA氧化损伤主要通过碱基切除修复（BER）修复。先前，我们的实验室发现，缺乏BER糖基酶Ogg1或Neil1的小鼠比野生型小鼠在局灶性缺血性中风中恢复得更差。在这里，一个小鼠模型被用来研究Xrcc1的两个等位基因中的一个的缺失是否会改变中风后的恢复。Xrcc1编码BER所需的非酶支架蛋白。与野生型小鼠相比，缺血再灌注对Xrcc1+/−小鼠的脑损伤更大，功能恢复更低。此外，更大比例的Xrcc1+/−小鼠因中风而死亡。对死于中风和死于非神经系统原因的人类个体的脑样本进行了脑损伤的各个步骤分析。研究发现，与对照组相比，脑卒中患者胸腺嘧啶乙二醇切口、基本核酸内切酶切口和单核苷酸结合活性明显丧失，XRCC1和NEIL1蛋白的表达也较低。综上所述，这些结果表明，BER受损是缺血性脑损伤的一个危险因素，并有助于其恢复。
Oxidative DNA damage is mainly repaired by base excision repair (BER). Previously, our lab showed that mice lacking the BER glycosylases Ogg1 or Neil1 recover more poorly from focal ischemic stroke than wild-type mice. Here, a mouse model was used to investigate whether loss of one of the two alleles of Xrcc1, which encodes a non-enzymatic scaffold protein required for BER, alters recovery from stroke. Ischemia and reperfusion caused higher brain damage and lower functional recovery in Xrcc1+/− mice than in wild-type mice. Additionally, a greater percentage of Xrcc1+/− mice died as a result of the stroke. Brain samples from human individuals who died of stroke and individuals who died of non-neurological causes were assayed for various steps of BER. Significant losses of thymine glycol incision, abasic endonuclease incision and single nucleotide incorporation activities were identified, as well as lower expression of XRCC1 and NEIL1 proteins in stroke brains compared to controls. Together, these results suggest that impaired BER is a risk factor in ischemic brain injury and contributes to its recovery.
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阿尔茨海默氏病线粒体裂解物的碱基切除DNA修复水平。
影响因子：
4.2
作者：
Canugovi C;Shamanna RA;Croteau DL;Bohr VA
通讯作者：
Bohr VA
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
30.8
作者：
Date, H;Onodera, O;Tsuji, S
通讯作者：
Tsuji, S
影响因子：
--
作者：
Dutra, Ana V. C.;Lin, Hsiu-Fen;Grewal, Raji P.
通讯作者：
Grewal, Raji P.
影响因子：
4.8
作者：
Katafuchi, A;Nakano, T;Ide, H
通讯作者：
Ide, H