Epigallocatechin gallate counteracts oxidative stress in docosahexaenoxic acid-treated myocytes
Epigallocatechin gallate counteracts oxidative stress in docosahexaenoxic acid-treated myocytes
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DOI：
10.1016/j.bbabio.2014.01.014
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发表时间：
2014-06-01
影响因子：
4.3
通讯作者：
Josepa Salvado, M.
中科院分区：
文献类型：
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作者：
Casanova, Ester;Baselga-Escudero, Laura;Josepa Salvado, M.
骨骼肌是哺乳动物能量代谢的关键器官，其线粒体是多功能细胞器，是膳食生物活性化合物的靶标。这项工作的目标是在 L6 肌细胞中使用二十二碳六烯酸 (DHA)、表没食子儿茶素没食子酸酯 (EGCG) 以及两者的组合来检查线粒体动力学、功能和细胞能量参数的调节。将化合物（25μM）温育4小时。用 DHA 培养的细胞显示出较少的耗氧量和较高的 ADP/ATP 比率水平，同时下调 Cox 和 Ant1 基因表达。 DHA 破坏能量稳态，增加细胞内活性氧 (ROS) 水平并降低线粒体膜电位。抵消 ROS 过量产生的防御机制是通过上调 Ucp2、Ucp3 和 MnSod 基因表达。此外，用DHA培养的肌细胞具有更高的线粒体质量，其中大而细长的线粒体比例更高，而裂变基因Drp1和Fiss1以及融合基因Mfn2被下调。在与 DHA 和 EGCG 共孵育的心肌细胞中，ROS 水平和二磷酸腺苷 (ADP)/三磷酸腺苷 (ATP) 比率与未处理的心肌细胞相似，耗氧量减少、线粒体质量增加以及 Ucp2 和 Ucp3 基因过表达与 DHA 处理的细胞相似，线粒体脱氧核糖核酸 (DNA) 量也较高，并且 Drp1 和 Fiss1 基因表达水平降低。总之，在 DHA 中添加 EGCG 使细胞在线粒体形态、能量和氧化还原状态方面恢复到对照条件，而这些在 DHA 处理的肌细胞中是不平衡的。 (C) 2014 Elsevier B.V. 保留所有权利。
Skeletal muscle is a key organ of mammalian energy metabolism, and its mitochondria are multifunction organelles that are targets of dietary bioactive compounds. The goal of this work was to examine the regulation of mitochondrial dynamics, functionality and cell energy parameters using docosahexaenoic acid (DHA), epigallocatechin gallate (EGCG) and a combination of both in L6 myocytes. Compounds (at 25 mu M) were incubated for 4 h. Cells cultured with DHA displayed less oxygen consumption with higher ADP/ATP ratio levels concomitant with downregulation of Cox and Ant1 gene expression. The disruption of energetic homeostasis by DHA, increases intracellular reactive oxygen species (ROS) levels and decreases mitochondrial membrane potential. The defence mechanism to counteract the excess of ROS production was by the upregulation of Ucp2, Ucp3 and MnSod gene expression. Moreover myocytes cultured with DHA had a higher mitochondrial mass with a higher proportion of large and elongated mitochondria, whereas the fission genes Drp1 and Fiss1 and the fusion gene Mfn2 were downregulated. In myocytes co-incubated with DHA and EGCG, ROS levels and the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio were similar to untreated myocytes and the decrease of oxygen consumption, higher mitochondrial mass and the overexpression of Ucp2 and Ucp3 genes were similar to the DHA-treated cells with also a higher amount of mitochondrial deoxyribonucleic acid (DNA), and reduced Drp1 and Fiss1 gene expression levels. In conclusion the addition of EGCG to DHA returned the cells to the control conditions in terms of mitochondrial morphology, energy and redox status, which were unbalanced in the DHA-treated myocytes. (C) 2014 Elsevier B.V. All rights reserved.