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首页> 外文期刊>Biochemistry and Cell Biology >Liver X receptor α is targeted by microRNA-1 to inhibit cardiomyocyte apoptosis through a ROS-mediated mitochondrial pathway
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Liver X receptor α is targeted by microRNA-1 to inhibit cardiomyocyte apoptosis through a ROS-mediated mitochondrial pathway

机译：肝X受体α由MicroRNA-1靶向，以通过ROS介导的线粒体途径抑制心肌细胞凋亡

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摘要

Diabetic cardiomyopathy (DCM) is defined as ventricular dysfunction occurring independently of a recognized cause such as hypertension or coronary artery disease. Liver X receptor α (LXRα), a subtype of ligand-activated transcription factors LXRs, has been considered as a potential pharmacological target in the pathogenesis of cardiovascular and metabolic diseases. However, the potential mechanism of how LXRα is regulated in cardiomyocytes is still unclear. This study investigated the effect of activating LXRα with GW3965 on cardiomyocyte apoptosis and its upstream regulator in glucose-induced H9C2 cells. Our data indicated that GW3965 up-regulated the expression of LXRα, inhibited cardiomyocyte apoptosis, and altered the apoptosis-related proteins in glucose-induced H9C2 cells. In addition, GW3965 restored the mitochondrial membrane potential level and decreased the ROS production induced by glucose. Moreover, LXRα was confirmed as a direct target of microRNA-1 (miR-1) that was involved in cardiomyocyte apoptosis of DCM, and overexpression of miR-1 abrogated the inhibiting effect of GW3965 on glucose-induced apoptosis in H9C2 cells. This study highlights an important role of LXRα in the development of DCM and brings new insights into the complex mechanisms involved in the pathogenesis of DCM.
机译：糖尿病心肌病（DCM）定义为室内功能障碍，独立于识别的原因如高血压或冠状动脉疾病。肝X受体α（LXRα）是配体活化转录因子LXRS的亚型，已被认为是心血管和代谢疾病发病机制中的潜在药理靶标。然而，LXRα如何在心肌细胞中调节LXRα的潜在机制尚不清楚。本研究研究了激活LXRα与GW3965对葡萄糖诱导的H9C2细胞心肌细胞凋亡及其上游调节剂的影响。我们的数据表明，GW3965上调LXRα的表达，抑制心肌细胞凋亡，并改变了葡萄糖诱导的H9C2细胞中的凋亡相关蛋白质。此外，GW3965还恢复了线粒体膜电位水平，并降低了葡萄糖诱导的ROS产生。此外，将LXRα确认为MicroRNA-1（miR-1）的直接靶，其参与DCM的心肌细胞凋亡，并且MIR-1的过度抑制废除GW3965对H9C2细胞中葡萄糖诱导的凋亡的抑制作用。本研究突出了LXRα在DCM开发中的重要作用，并为DCM发病机制中的复杂机制带来了新的洞察力。

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  • 来源
    《Biochemistry and Cell Biology》 |2018年第1期|共8页
  • 作者

    Yongxia Cheng; Dawei Zhang; Min Zhu; Ying Wang; Sufen Guo; Biao Xu; Guangyu Hou; Yukuan Feng; Guibo Liu;

  • 作者单位

    Department of Pathology Mudanjiang Medical College Mudanjiang Heilongjiang Province 157011;

    Department of Anatomy Mudanjiang Medical College Mudanjiang Heilongjiang Province 157011 People;

    Department of Medical Imaging Hongqi Hospital Mudanjiang Medical College Mudanjiang;

    Department of Anatomy Mudanjiang Medical College Mudanjiang Heilongjiang Province 157011 People;

    Department of Pathology Mudanjiang Medical College Mudanjiang Heilongjiang Province 157011;

    Department of Cardiology Hongqi Hospital Mudanjiang Medical College Mudanjiang Heilongjiang;

    Department of Medical Function Mudanjiang Medical College Mudanjiang Heilongjiang Province;

    Department of Anatomy Mudanjiang Medical College Mudanjiang Heilongjiang Province 157011 People;

    Department of Anatomy Mudanjiang Medical College Mudanjiang Heilongjiang Province 157011 People;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    diabetic cardiomyopathy; liver X receptor α; microRNA-1; apoptosis; reactive oxygen species;

    机译：糖尿病心肌病;肝X受体α;microRNA-1;细胞凋亡;反应性氧;

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