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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.
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Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.

机译:白介素-6是小鼠酒精性肝损伤后线粒体DNA修复的重要介质。

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摘要

We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL-6 knockout (KO) and wild-type (WT) mice. Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8-OHdG) in both IL-6KO and WT mice. However, the WT mice were able to repair the injury by increased production of mtDNA repair enzymes (OGG-1, Neil 1) and check point (p21, p53) proteins and avoid the mtDNA mutations. By contrast the IL-6 KO mice were unable to repair mtDNA resulting in deletions and diminished transcription of the mtDNA encoded protein cytochrome c oxidase subunit-I (COI). The mitochondrial injury was reflected by decreased membrane potential, reduced levels of ATP, and apoptosis-inducing factor (AIF)-induced apoptosis. Conclusion: IL-6 plays a critical role in allowing the liver to recover from significant mtDNA oxidation caused by alcohol. The data suggests that IL-6 activates mtDNA repair enzymes and induces cell cycle arrest allowing time for mtDNA repair.
机译:我们研究了以下假设:慢性乙醇消耗的主要影响是线粒体DNA(mtDNA)损伤,并在IL-6基因敲除(KO)和野生型(WT)小鼠中比较了这种损伤。在IL-6KO和WT小鼠中,乙醇喂养4周导致脂肪变性和mtDNA氧化损伤(8-OHdG)。但是,野生型小鼠能够通过增加mtDNA修复酶(OGG-1,Neil 1)和检查点(p21,p53)蛋白的产生来修复损伤,并避免mtDNA突变。相比之下,IL-6 KO小鼠无法修复mtDNA,导致mtDNA编码的蛋白细胞色素C氧化酶亚基(COI)缺失和转录减少。膜电位降低,ATP水平降低以及凋亡诱导因子(AIF)诱导的凋亡反映了线粒体损伤。结论:IL-6在使肝脏从酒精引起的明显mtDNA氧化中恢复中起着关键作用。数据表明,IL-6激活mtDNA修复酶并诱导细胞周期停滞,从而有时间进行mtDNA修复。

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