SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a Guardian of Genomic DNA
SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a Guardian of Genomic DNA
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DOI：
10.4061/2010/795946
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发表时间：
2010-01-01
影响因子：
2.3
通讯作者：
Enomoto, Takemi
中科院分区：
文献类型：
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作者：
Inoue, Eri;Tano, Keizo;Enomoto, Takemi
活性氧（Reactive oxygen species, ROSs）是在正常细胞代谢过程中产生的，尤其是线粒体的呼吸作用，这些活性氧被认为会对大分子（包括DNA）造成氧化损伤。在我们之前的论文中，我们没有发现任何迹象表明线粒体超氧化物歧化酶SOD2的消耗会导致DNA损伤的增加。本文研究了分布于细胞质、细胞核和线粒体膜间隙的SOD1。我们从鸡DT40细胞中产生条件SOD1敲除细胞并分析其表型。结果表明，SOD1对生存能力至关重要，SOD1的消耗，特别是核SOD1的消耗，增加了姐妹染色单体交换（SCE）的频率，这表明超氧化物在核内或核附近产生，核SOD1起着基因组守护者的作用。此外，我们发现抗坏血酸可以抵消SOD1缺失引起的缺陷，包括细胞致命性、SCE频率和无尿嘧啶/无嘧啶位点的增加。
Reactive oxygen species (ROSs) are produced during normal cellular metabolism, particularly by respiration in mitochondria, and these ROSs are considered to cause oxidative damage to macromolecules, including DNA. In our previous paper, we found no indication that depletion of mitochondrial superoxide dismutase, SOD2, resulted in an increase in DNA damage. In this paper, we examined SOD1, which is distributed in the cytoplasm, nucleus, and mitochondrial intermembrane space. We generated conditional SOD1 knockout cells from chicken DT40 cells and analyzed their phenotypes. The results revealed that SOD1 was essential for viability and that depletion of SOD1, especially nuclear SOD1, increased sister chromatid exchange (SCE) frequency, suggesting that superoxide is generated in or near the nucleus and that nuclear SOD1 functions as a guardian of the genome. Furthermore, we found that ascorbic acid could offset the defects caused by SOD1 depletion, including cell lethality and increases in SCE frequency and apurinic/apyrimidinic sites.