Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.
Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.
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DOI：
10.1002/hep.23909
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发表时间：
2010-12
期刊：
影响因子：
13.5
通讯作者：
Sun, Zhaoli
中科院分区：
文献类型：
--
作者：
Zhang, Xiuying;Tachibana, Shingo;Wang, Hua;Hisada, Masayuki;Williams, George Melville;Gao, Bin;Sun, Zhaoli
我们研究了慢性乙醇消耗的一个显着影响是线粒体DNA（mtDNA）损伤的假设，并比较了IL-6敲除（KO）和野生型（WT）小鼠的这种损伤。在IL-6 KO和WT小鼠中，乙醇喂养4周导致脂肪变性和氧化性mtDNA损伤（8-OHdG）。然而，WT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小鼠不能修复mtDNA，导致mtDNA编码的蛋白质细胞色素c氧化酶亚基I（COI）缺失和转录减少。线粒体损伤表现为膜电位降低、ATP水平降低和凋亡诱导因子（AIF）诱导的细胞凋亡。IL-6在允许肝脏从酒精引起的显著mtDNA氧化中恢复方面起着关键作用。这些数据表明，IL-6激活mtDNA修复酶并诱导细胞周期停滞，从而为mtDNA修复提供时间。
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. 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.
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