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Interleukin‐6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice
Author(s) -
Zhang Xiuying,
Tachibana Shingo,
Wang Hua,
Hisada Masayuki,
Williams George Melville,
Gao Bin,
Sun Zhaoli
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23909
Subject(s) - mitochondrial dna , biology , cytochrome c oxidase , mitochondrion , liver injury , dna repair , microbiology and biotechnology , knockout mouse , gene , genetics , endocrinology
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. (H EPATOLOGY 2010;)