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首页> 外文期刊>BioMed research international >7,8-Dihydroxyflavone Suppresses Oxidative Stress-Induced Base Modification in DNA via Induction of the Repair Enzyme 8-Oxoguanine DNA Glycosylase-1
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7,8-Dihydroxyflavone Suppresses Oxidative Stress-Induced Base Modification in DNA via Induction of the Repair Enzyme 8-Oxoguanine DNA Glycosylase-1

机译：7,8-二羟基黄酮通过修复酶8-氧鸟嘌呤DNA糖基化酶-1的诱导抑制DNA中氧化应激诱导的碱基修饰。

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摘要

The modified guanine base 8-oxoguanine (8-oxoG) is abundantly produced by oxidative stress, can contribute to carcinogenesis, and can be removed from DNA by 8-oxoguanine DNA glycosylase-1 (OGG1), which acts as an 8-oxoG glycosylase and endonudease. This study investigated the mechanism by which 7,8-dihydroxyflavone (DHF) inhibits oxidative stress-induced 8-oxoG formation in hamster lung fibroblasts (V79-4). DHF significantly reduced the amount of 8-oxoG induced by hydrogen peroxide (H_2O_2) and elevated the levels of OGG1 mRNA and protein. DHF increased the binding of nuclear factor erythroid 2-related factor 2 (Nrf2) to antioxidant response element sequences in the upstream promoter region of 0GG1. Moreover, DHF increased the nuclear levels of Nrf2, small Maf proteins, and the Nrf2/small Maf complex, all of which are decreased by H_2O_2 treatment. Likewise, the level of phosphorylated Akt, which activates Nrf2, was decreased by H_2O_2 treatment but restored by DHF treatment. The levels of 0GG1 and nuclear translocation of Nrf2 protein were decreased upon treatment with PI3K inhibitor or Akt inhibitor, and DHF treatment did not restore 0GG1 and nuclear Nrf2 levels in these inhibitor-treated cells. Furthermore, PI3K and Akt inhibitors abolished the protective effects of DHF in cells undergoing oxidative stress. These data indicate that DHF induces OGG1 expression via the PBK-Akt pathway and protects cells against oxidative DNA base damage by activating DNA repair systems.
机译：修饰的鸟嘌呤碱基8-氧代鸟嘌呤（8-oxoG）通过氧化应激大量产生，可以促进癌变，并可以通过8-氧代鸟嘌呤DNA糖基化酶-1（OGG1）从DNA中去除，该酶充当8-氧代G糖基化酶。和内在酶。这项研究调查了机制，其中7,8-二羟基黄酮（DHF）抑制仓鼠肺成纤维细胞（V79-4）中氧化应激诱导的8-oxoG形成。 DHF显着降低了过氧化氢（H_2O_2）诱导的8-oxoG量，并提高了OGG1 mRNA和蛋白质的水平。 DHF增加了核因子红系2相关因子2（Nrf2）与0GG1上游启动子区域中的抗氧化剂反应元件序列的结合。此外，DHF增加了Nrf2，Maf小蛋白和Nrf2 / Maf小复合物的核水平，所有这些都通过H_2O_2处理而降低。同样，激活Nrf2的磷酸化Akt的水平通过H_2O_2处理降低，但通过DHF处理得以恢复。用PI3K抑制剂或Akt抑制剂处理后，0GG1的水平和Nrf2蛋白的核易位降低，并且DHF处理不能使这些抑制剂处理的细胞恢复0GG1和Nrf2的核水平。此外，PI3K和Akt抑制剂消除了DHF对遭受氧化应激的细胞的保护作用。这些数据表明，DHF通过PBK-Akt途径诱导OGG1表达，并通过激活DNA修复系统保护细胞免受氧化性DNA碱基的破坏。

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