The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression
The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression
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DOI：
10.1016/j.pnpbp.2017.06.036
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发表时间：
2018-01-03
影响因子：
5.6
通讯作者：
Sliwinski, Tomasz
中科院分区：
文献类型：
--
作者：
Czarny, Piotr;Wigner, Paulina;Sliwinski, Tomasz
越来越多的证据表明，炎症、线粒体功能障碍和氧化-抗氧化失衡可能在抑郁症的发生和发展中发挥重要作用。氧化剂-抗氧化剂失衡导致的活性氧和氮物种水平的升高可能会导致包括DNA在内的生物分子的损伤增加。在我们团队和其他科学家进行的一项研究中，这一点在抑郁症患者中得到了证实。在患者的淋巴细胞、尿液和血清中发现了8-氧鸟嘌呤--DNA氧化损伤的标志。这些结果通过对淋巴细胞的彗星试验得到了证实。此外，研究表明，患者细胞修复过氧化氢诱导的DNA损伤的效率低于对照组细胞，参与DNA氧化损伤修复的基因的一些单核苷酸多态(SNP)可能调节抑郁症的风险。最后，在患者中观察到的DNA损伤修复效率较低，至少部分归因于特定SNP变异的存在，这一点通过基因-表型分析揭示。综上所述，现有文献表明，氧化应激和DNA损伤修复效率低下都可能导致抑郁症患者DNA损伤增加。类似的机制可能会导致线粒体功能障碍，这在抑郁症中可以观察到。
A growing body of evidence suggests that inflammation, mitochondrial dysfunction and oxidant-antioxidant imbalance may play a significant role in the development and progression of depression. Elevated levels of reactive oxygen and nitrogen species - a result of oxidant-antioxidant imbalance - may lead to increased damage of biomolecules, including DNA. This was confirmed in depressed patients in a research study conducted by our team and other scientists. 8-oxoguanine - a marker of oxidative DNA damage - was found in the patients' lymphocytes, urine and serum. These results were confirmed using a comet assay on lymphocytes. Furthermore, it was shown that the patients' cells repaired peroxide-induced DNA damage less efficiently than controls' cells and that some single nucleotide polymorphisms (SNP) of the genes involved in oxidative DNA damage repair may modulate the risk of depression. Lastly, less efficient DNA damage repair observed in the patients can be, at least partly, attributed to the presence of specific SNP variants, as it was revealed through a genotype-phenotype analysis. In conclusion, the available literature shows that both oxidative stress and less efficient DNA damage repair may lead to increased DNA damage in depressed patients. A similar mechanism may result in mitochondrial dysfunction, which is observed in depression.