Targeting truncated APEI in mitochondria enhances cell survival after oxidative stress
Targeting truncated APEI in mitochondria enhances cell survival after oxidative stress
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靶向线粒体中截短的 APEI 可增强氧化应激后细胞的存活率
DOI：
10.1016/j.freeradbiomed.2008.05.007
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发表时间：
2008-09-01
影响因子：
7.4
通讯作者：
Qing, Yi
中科院分区：
文献类型：
--
作者：
Li, Meng-Xia;Wang, Dong;Qing, Yi
线粒体DNA （mtDNA）氧化损伤的高稳态水平被认为是线粒体对DNA损伤攻击的高易感性和DNA修复能力有限的结果。作为碱基切除修复（BER）的关键酶，APEI在线粒体中通常是稀缺的。线粒体靶向的APEI具有强大的修复活性，是一种很有前途的治疗候选者。本研究构建线粒体靶向截断型APE1 （mtAPE1）和全长型APE1 （flAPE1）过表达载体，转染人脐静脉内皮细胞，检测其过氧化氢诱导氧化应激后的保护作用。截断的APEI在转染mtape1细胞的线粒体中实现了蛋白和酶活性水平的过表达。同时，观察到增强的mtDNA修复能力和增加的细胞存活率。转染MtAPE1也通过阻断线粒体依赖通路来阻止细胞凋亡。相比之下，转染flAPE1可使细胞核APE]蛋白水平和细胞核APE活性轻微升高，但对细胞抗氧化应激无明显作用。目前的结果表明，线粒体中截断的APE1的过表达似乎是保护健康细胞免受氧化应激某些有害影响的可行方法。(c) 2008爱思唯尔公司版权所有。
The high steady-state level of mitochondrial DNA (mtDNA) oxidative lesions is assumed to be the result of high susceptibility to DNA damage attack and limited DNA repair capacity in mitochondria. As a key enzyme of base excision repair (BER), human apurinic/apyrimidinic endonuclease (APEI) is often scarce in mitochondria. and mitochondria-targeted APEI with robust repair activity represents a promising therapeutic candidate. In this study, overexpression vectors of mitochondria-targeted truncated APE] (mtAPE1) and that of full-length APE1 (flAPE1) were constructed and transfected to human umbilical vein endothelial cells to test their protective effects after hydrogen peroxide-induced oxidative stress. The overexpression of truncated APEI was achieved at protein and enzyme activity levels in mitochondria of mtAPE1-transfected cells. In parallel, enhanced mtDNA repair capacity and increased cell survival were observed. MtAPE1 transfection also prevented apoptosis by blocking mitochondria-dependent pathways. In contrast, flAPE1 transfection rendered slight elevation of nuclear APE] protein level and nuclear APE activity but no benefits for cell resistance to oxidative stress. The present results Suggest that overexpression of the truncated APE1 in mitochondria appears to be a viable approach to protecting healthy cells from some deleterious effects of oxidative stress. (c) 2008 Elsevier Inc. All rights reserved.