Mitochondrial DNA Oxidative Damage Contributes to Cardiomyocyte Ischemia/Reperfusion-Injury in Rats: Cardioprotective Role of Lycopene
Mitochondrial DNA Oxidative Damage Contributes to Cardiomyocyte Ischemia/Reperfusion-Injury in Rats: Cardioprotective Role of Lycopene
复制标题
线粒体 DNA 氧化损伤导致大鼠心肌细胞缺血/再灌注损伤：番茄红素的心脏保护作用
DOI：
10.1002/jcp.24941
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发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Zeng, Chunyu
中科院分区：
文献类型：
--
作者：
Yue, Rongchuan;Xia, Xuewei;Zeng, Chunyu
线粒体功能障碍和氧化应激参与了缺血再灌注损伤的发病机制。番茄红素是一种主要存在于西红柿和其他蔬菜和水果中的亲脂性抗氧化剂，可以保护线粒体DNA免受氧化损伤。然而，线粒体DNA在心肌I/R损伤中的作用尚不清楚。在本研究中，我们旨在确定番茄红素是否以及如何保护心肌细胞免受I/R损伤。在体内外实验中，心肌细胞线粒体8-羟基鸟嘌呤(8-OHdG)含量增加，线粒体DNA含量和转录水平降低，线粒体功能障碍。番茄红素可阻断I/R损伤对心肌细胞的上述作用。仅线粒体DNA耗尽就足以导致心肌细胞死亡。缺血再灌注损伤使线粒体转录关键激活物线粒体转录因子A(TfAM)的蛋白水平降低，而番茄红素可阻断TfAM的表达。番茄红素对线粒体DNA的保护作用与减少线粒体ROS的产生和稳定Tfam有关。综上所述，番茄红素可保护心肌细胞免受I/R损伤所致的线粒体DNA氧化损伤。J.细胞。物理。2015年，230：2128-2141。(C)2015年威利期刊公司。
Mitochondrial (mt) dysfunction and oxidative stress are involved in the pathogenesis of ischemia/reperfusion (I/R)-injury. Lycopene, a lipophilic antioxidant found mainly in tomatoes and in other vegetables and fruits, can protect mtDNA against oxidative damage. However, the role of mtDNA in myocardial I/R-injury is unclear. In the present study, we aimed to determine if and how lycopene protects cardiomyocytes from I/R-injury. In both in vitro and in vivo studies, I/R-injury increased mt 8-hydroxyguanine (8-OHdG) content, decreased mtDNA content and mtDNA transcription levels, and caused mitochondrial dysfunction in cardiomyocytes. These effects of I/R injury on cardiomycoytes were blocked by pre-treatment with lycopene. MtDNA depletion alone was sufficient to induce cardiomyocyte death. I/R-injury decreased the protein level of a key activator of mt transcription, mitochondrial transcription factor A (Tfam), which was blocked by lycopene. The protective effect of lycopene on mtDNA was associated with a reduction in mitochondrial ROS production and stabilization of Tfam. In conclusion, lycopene protects cardiomyocytes from the oxidative damage of mtDNA induced by I/R-injury. J. Cell. Physiol. 230: 2128-2141, 2015. (c) 2015 Wiley Periodicals, Inc.