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芦丁抑制动力相关蛋白1(DRP1)介导的线粒体分裂,并预防乙醇诱导的HepG2细胞和斑马鱼的肝毒性。

Rutin inhibits DRP1-mediated mitochondrial fission and prevents ethanol-induced hepatotoxicity in HepG2 cells and zebrafish.

作者信息

Choi Youngsook, Seo Heymin, Cho Mina, Kim Joohee, Chung Hak Suk, Lee Icksoo, Kim Min Jung

机构信息

Research Institute of Women's Health, Sookmyung Women's University, Seoul, Korea.

Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.

出版信息

Anim Cells Syst (Seoul). 2021 Feb 11;25(1):74-81. doi: 10.1080/19768354.2021.1882565.

DOI:10.1080/19768354.2021.1882565
PMID:33717419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7935124/
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.

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个器官系统有害,如中枢神经系统、骨骼肌和肝脏,会引发酒精诱导的疾病如癌症,还会导致肝毒性和酒精性肌病。酒精暴露会导致肝脏酒精代谢和氧消耗激增,肝ATP减少,以及肝细胞内脂质快速积累。几种病理状况与由异常线粒体功能和细胞稳态引发的线粒体动力学缺陷密切相关,这增加了靶向线粒体动力学的新型药物可能具有治疗潜力以恢复乙醇诱导的肝毒性中细胞稳态的可能性。芦丁是一种已知能保护细胞免受细胞毒性化学物质影响的植物化学多酚。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分裂和恢复线粒体动力学平衡来增强线粒体动力学。用芦丁处理乙醇暴露细胞后线粒体伸长伴随着动力相关蛋白1(DRP1)表达降低。这些数据表明芦丁在重塑线粒体动力学以减轻肝脂肪变性、增强线粒体功能和细胞活力方面发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/078ef77da082/TACS_A_1882565_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/c0f96d8caeac/TACS_A_1882565_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/193fe6d531b5/TACS_A_1882565_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/0288b186613e/TACS_A_1882565_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/cc8d985b9d80/TACS_A_1882565_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/078ef77da082/TACS_A_1882565_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/c0f96d8caeac/TACS_A_1882565_F0001_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/193fe6d531b5/TACS_A_1882565_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/0288b186613e/TACS_A_1882565_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/cc8d985b9d80/TACS_A_1882565_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f35/7935124/078ef77da082/TACS_A_1882565_F0005_OC.jpg

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