Mitochondrial and nuclear DNA damage and repair in age-related macular degeneration.
Mitochondrial and nuclear DNA damage and repair in age-related macular degeneration.
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DOI：
10.3390/ijms14022996
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发表时间：
2013-01-31
影响因子：
5.6
通讯作者：
Kaarniranta K
中科院分区：
文献类型：
--
作者：
Blasiak J;Glowacki S;Kauppinen A;Kaarniranta K
衰老和氧化应激似乎是老年性黄斑变性(AMD)发病机制中最重要的因素，AMD是一种影响发达国家许多老年人的疾病。然而，衰老与包括DNA在内的许多生物分子中氧化损伤的积累有关。此外，线粒体在这一过程中可能特别重要，因为在其电子传输链中产生的活性氧物种可以破坏细胞成分。因此，细胞对DNA损伤的反应，主要通过DNA修复表达，可能在AMD的病因中发挥重要作用。在一些研究中，线粒体DNA(MtDNA)损伤和突变的增加以及DNA修复效率的降低与AMD的发生和分期有关。也有研究表明，在AMD中，线粒体DNA比核DNA积累了更多的DNA损伤。然而，线粒体中的DNA损伤反应是由核编码蛋白执行的，因此核DNA(NDNA)的突变可能会影响其线粒体对突变的反应能力。我们报道了AMD患者的淋巴细胞表现出更高的总内源性基础DNA损伤和氧化性DNA损伤，对过氧化氢和紫外线辐射表现出更高的敏感性，并且修复这些因素引起的损伤的效率低于来自对照组的细胞。我们推测，当视网膜色素上皮细胞对环境应激因素的敏感性增强时，DNA修复的不良效果(即特定年龄的高于平均水平的受损)有助于AMD的发病。总之，这些数据表明，细胞对线粒体和核DNA损伤的反应可能在AMD的发病机制中发挥重要作用。
Aging and oxidative stress seem to be the most important factors in the pathogenesis of age-related macular degeneration (AMD), a condition affecting many elderly people in the developed world. However, aging is associated with the accumulation of oxidative damage in many biomolecules, including DNA. Furthermore, mitochondria may be especially important in this process because the reactive oxygen species produced in their electron transport chain can damage cellular components. Therefore, the cellular response to DNA damage, expressed mainly through DNA repair, may play an important role in AMD etiology. In several studies the increase in mitochondrial DNA (mtDNA) damage and mutations, and the decrease in the efficacy of DNA repair have been correlated with the occurrence and the stage of AMD. It has also been shown that mitochondrial DNA accumulates more DNA lesions than nuclear DNA in AMD. However, the DNA damage response in mitochondria is executed by nucleus-encoded proteins, and thus mutagenesis in nuclear DNA (nDNA) may affect the ability to respond to mutagenesis in its mitochondrial counterpart. We reported that lymphocytes from AMD patients displayed a higher amount of total endogenous basal and oxidative DNA damage, exhibited a higher sensitivity to hydrogen peroxide and UV radiation, and repaired the lesions induced by these factors less effectively than did cells from control individuals. We postulate that poor efficacy of DNA repair (i.e., is impaired above average for a particular age) when combined with the enhanced sensitivity of retinal pigment epithelium cells to environmental stress factors, contributes to the pathogenesis of AMD. Collectively, these data suggest that the cellular response to both mitochondrial and nuclear DNA damage may play an important role in AMD pathogenesis.
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与年龄相关的黄斑变性中DNA修复蛋白的遗传变异性。
影响因子：
5.6
作者：
Blasiak J;Synowiec E;Salminen A;Kaarniranta K
通讯作者：
Kaarniranta K
影响因子：
4.2
作者：
Feher, Janos;Kovacs, Illes;Gabrieli, Corrado Balacco
通讯作者：
Gabrieli, Corrado Balacco
影响因子：
14.9
作者：
Boesch, Pierre;Ibrahim, Noha;Lightowlers, Robert N.
通讯作者：
Lightowlers, Robert N.
影响因子：
37.8
作者：
Durik M;Kavousi M;van der Pluijm I;Isaacs A;Cheng C;Verdonk K;Loot AE;Oeseburg H;Bhaggoe UM;Leijten F;van Veghel R;de Vries R;Rudez G;Brandt R;Ridwan YR;van Deel ED;de Boer M;Tempel D;Fleming I;Mitchell GF;Verwoert GC;Tarasov KV;Uitterlinden AG;Hofman A;Duckers HJ;van Duijn CM;Oostra BA;Witteman JC;Duncker DJ;Danser AH;Hoeijmakers JH;Roks AJ
通讯作者：
Roks AJ
DOI：
10.1007/978-94-007-2869-1_7
发表时间：
2012-01-01
期刊：
ADVANCES IN MITOCHONDRIAL MEDICINE
影响因子：
--
作者：
Estaquier, Jerome;Vallette, Francois;Mignotte, Bernard
通讯作者：
Mignotte, Bernard