miR-33s在NF-κB抑制ABCA1表达及胆固醇流出中的作用
DOI:
作者:
作者单位:

桂林医学院组胚教研室,桂林医学院教务处,桂林医学院组胚教研室,桂林医学院组胚教研室

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金项目(81660082)和广西高校中青年教师基础能力提升项目(KY2016LX597)资助


The Role of miR-33s in ABCA1 Expression and Cholesterol Efflux Suppression Induced by Nuclear Factor-kappaB
Author:
Affiliation:

Guilin Medical University,Guilin Medical University,Guilin Medical University,Guilin Medical University

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China (81660082) and Project of Improving Basic Skills of Young Teachers in Guangxi Colleges and Universities (KY2016LX597)

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    为探讨miR-33s在核因子κB(NF-κB)抑制三磷酸腺苷结合盒转运体A1(ABCA1)表达及胆固醇流出中的作用,THP-1巨噬细胞源性泡沫细胞经不同浓度脂多糖(LPS)处理,活化NF-κB,或以PDTC(NF-κB抑制剂)预处理细胞后再加入LPS,实时荧光定量PCR检测细胞miR-33s及其宿主基因胆固醇调节元件结合蛋白(SREBPs)的表达,蛋白质印迹法检测SREBPs的蛋白质表达,染色体免疫共沉淀检测NF-κB p65与SREBPs启动子区结合情况;LPS处理基础上,转染miR-33s抑制物或miR-33s模拟物,RT-PCR检测ABCA1 mRNA表达水平,蛋白质印迹法检测ABCA1蛋白水平,液体闪烁计数仪检测细胞内的胆固醇流出.结果显示,NF-κB活化促进miR-33s及SREBPs的表达,使用PDTC抑制NF-κB,细胞内miR-33s和SREBPs的表达下降;NF-κB p65可与SREBPs启动子区直接结合;转染miR-33s抑制剂后,NF-κB活化对ABCA1的抑制作用减弱,胆固醇流出增强;相反,转染miR-33s抑制物,NF-κB活化对ABCA1的抑制作用增强,胆固醇流出减弱.结果提示,NF-κB活化可促进miR-33s表达,抑制ABCA1及胆固醇流出.

    Abstract:

    To investigate the role of miR-33s in the inhibition of ATP-binding cassette transporter A1 (ABCA1) expression and cholesterol efflux induced by NF-κB, THP-1 macrophage-derived foam cells were treated with different concentrations of LPS to activate NF-κB with or without PDTC (NF-κB inhibitors),the mRNA expression of miR-33s and its host gene SREBPs were detected by RT-PCR, the proteins expression of SREBPs were detected by Western blot, the binding capacifies of NF-κB p65 to SREBPs promoters were detected by chromatin immunoprecipitation. After cells were treated with LPS, miR-33s inhibitor or mimic were transfected, ABCA1 mRNA and protein were detected by RT-PCR and Western blot, respectively. The cholesterol efflux was detected by liquid scintillation counter. The results showed that expression of miR-33s and SREBPs were increased by NF-κB activation and decreased by adding PDTC. NF-κB p65 could directly combine with the SREBPs promoter. After transfected with miR-33s inhibitor, the inhibitory effect of NF-κB activation on ABCA1 expression was weakened, and cholesterol efflux was increased. On the contrary, the inhibitory effect on ABCA1 strengthened and cholesterol efflux decreased after transfected by miR-33s mimic. These results suggested that NF-κB activation could promote miR-33s expression, inhibit ABCA1 expression and cholesterol efflux.

    参考文献
    相似文献
    引证文献
引用本文

陈筠,江婷,李孟奇,赵国军. miR-33s在NF-κB抑制ABCA1表达及胆固醇流出中的作用[J].生物化学与生物物理进展,2018,45(5):553-559

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2017-11-01
  • 最后修改日期:2017-12-26
  • 接受日期:2018-03-26
  • 在线发布日期: 2018-03-27
  • 出版日期: 2018-05-20