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Rutin inhibits DRP1-mediated mitochondrial fission and prevents ethanol-induced hepatotoxicity in HepG2 cells and zebrafish
Animal Cells and Systems ( IF 2.9 ) Pub Date : 2021-02-11 , DOI: 10.1080/19768354.2021.1882565
Youngsook Choi 1 , Heymin Seo 1 , Mina Cho 2 , Joohee Kim 2 , Hak Suk Chung 3, 4 , Icksoo Lee 5 , Min Jung Kim 2
Affiliation  

ABSTRACT

Excessive alcohol consumption causes the cellular and tissue damage. The toxic metabolites of ethanol are harmful to multiple organ systems, such as the central nervous system, skeletal muscles, and liver, and cause alcohol-induced diseases like cancer, as well as induce hepatotoxicity, and alcoholic myopathy. Alcohol exposure leads to a surge in hepatic alcohol metabolism and oxygen consumption, a decrease in hepatic ATP, and the rapid accumulation of lipid within hepatocytes. Several pathologies are closely linked to defective mitochondrial dynamics triggered by abnormal mitochondrial function and cellular homeostasis, raising the possibility that novel drugs targeting mitochondrial dynamics may have therapeutic potential in restoring cellular homeostasis in ethanol-induced hepatotoxicity. Rutin is a phytochemical polyphenol known to protect cells from cytotoxic chemicals. We investigated the effects of rutin on mitochondrial dynamics induced by ethanol. We found that rutin enhances mitochondrial dynamics by suppressing mitochondrial fission and restoring the balance of the mitochondrial dynamics. Mitochondrial elongation following rutin treatment of ethanol exposed cells was accompanied by reduced DRP1 expression. These data suggest that rutin plays an important role in remodeling of mitochondrial dynamics to alleviate hepatic steatosis and enhance mitochondrial function and cell viability.



中文翻译:

芦丁抑制DRP1介导的线粒体裂变并防止乙醇诱导的HepG2细胞和斑马鱼肝毒性

摘要

过量饮酒会导致细胞和组织损伤。乙醇的有毒代谢产物对多种器官系统(例如中枢神经系统,骨骼肌和肝脏)有害,并导致酒精引起的疾病(如癌症),并引起肝毒性和酒精性肌病。酒精暴露会导致肝脏酒精代谢和氧气消耗激增,肝脏ATP降低以及肝细胞内脂质的快速积累。几种病理学与由异常线粒体功能和细胞稳态引起的线粒体动力学缺陷密切相关,从而增加了针对线粒体动力学的新药可能具有恢复乙醇引起的肝毒性的细胞稳态的治疗潜力的可能性。芦丁是一种植物化学多酚,已知可以保护细胞免受细胞毒性化学物质的侵害。我们研究了芦丁对乙醇诱导的线粒体动力学的影响。我们发现芦丁通过抑制线粒体裂变并恢复线粒体动力学平衡来增强线粒体动力学。芦丁处理乙醇暴露的细胞后线粒体伸长伴随着DRP1表达降低。这些数据表明,芦丁在线粒体动力学重塑中起着重要作用,以减轻肝脏脂肪变性并增强线粒体功能和细胞活力。我们发现芦丁通过抑制线粒体裂变并恢复线粒体动力学平衡来增强线粒体动力学。芦丁处理乙醇暴露的细胞后线粒体伸长伴随着DRP1表达降低。这些数据表明,芦丁在线粒体动力学重塑中起着重要作用,以减轻肝脏脂肪变性并增强线粒体功能和细胞活力。我们发现芦丁通过抑制线粒体裂变并恢复线粒体动力学平衡来增强线粒体动力学。芦丁处理乙醇暴露的细胞后线粒体伸长伴随着DRP1表达降低。这些数据表明,芦丁在线粒体动力学重塑中起着重要作用,以减轻肝脏脂肪变性并增强线粒体功能和细胞活力。

更新日期:2021-03-04
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