Senescence-associated decline in the intranuclear accumulation hOGG1-α and impaired 8-oxo-dG repair activity in senescing normal human oral keratinocytes in vivo
Senescence-associated decline in the intranuclear accumulation hOGG1-α and impaired 8-oxo-dG repair activity in senescing normal human oral keratinocytes in vivo
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DOI：
10.1016/j.yexcr.2005.07.019
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发表时间：
2005-10-15
影响因子：
3.7
通讯作者：
Park, NH
中科院分区：
文献类型：
--
作者：
Kang, MK;Kim, RH;Park, NH
我们确定了正常人口腔角质形成细胞（NHOK）衰老过程中的线粒体膜状态，活性氧（ROS）的存在和氧化DNA加合物的形成。衰老细胞显示出细胞内ROS和7，8-二氢-8-氧代-2 '-脱氧鸟苷（8-氧代-dG）（一种主要的氧化DNA加合物）的积累。细胞暴露于H2 O2诱导细胞DNA中的8-oxo-dG积累，其在复制NHOK中被迅速去除。然而，8-氧代-dG去除活性在衰老培养物中几乎完全消除。复制和衰老的NHOK都表达容易检测到的8-氧代-dG DNA糖基化酶（hOGG 1），该酶负责8-氧代-dG的糖苷切割。然而，暴露于H2 O2后，hOGG 1-α亚型的核内水平在衰老过程中降低，但在复制NHOK过程中没有降低。这些结果表明，衰老的NHOK积累氧化DNA损伤的部分原因是内源性ROS水平的增加和受损的hOGG 1酶的核内易位后暴露于氧化应激。(c)2005年爱思唯尔公司All rights reserved.
We determined the mitochondrial membrane status, presence of reactive oxygen species (ROS), and oxidative DNA adduct formation in normal human oral keratinocytes (NHOK) during senescence. The senescent cells showed accumulation of intracellular ROS and 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG), a major oxidative DNA adduct. Exposure of cells to H2O2 induced 8-oxo-dG accumulation in cellular DNA, which was rapidly removed in replicating NHOK. However, the 8-oxo-dG removal activity was almost completely abolished in the senescing culture. Both replicating and senescing NHOK expressed readily detectable 8-oxo-dG DNA glycosylase (hOGG1), the enzyme responsible for glycosidic cleavage of 8-oxo-dG. After exposure to H2O2, however, the intranuclear level of the hOGG1-alpha isoform was decreased in senescing but not in replicating NHOK. These results indicated that senescing NHOK accumulated oxidative DNA lesions in part due to increased level of endogenous ROS and impaired intranuclear translocation of hOGG1 enzyme upon exposure to oxidative stress. (c) 2005 Elsevier Inc. All rights reserved.