首页 > 过刊浏览>2015年第42卷第9期 >825-832
PDF HTML阅读 XML下载 导出引用 引用提醒
研究: PCSK9/LDLR通路介导姜黄素烟酸酯促进HepG2摄取脂质
DOI:
作者:
作者单位:

南华大学,湖南中医药大学，干细胞中药调控与应用研究室,湖南中医药大学，干细胞中药调控与应用研究室;中国－卢森堡中医药合作研究中心,南华大学，药学与生物科学学院,湖南中医药大学，干细胞中药调控与应用研究室,南华大学，药学与生物科学学院,湖南中医药大学，干细胞中药调控与应用研究室;中国－卢森堡中医药合作研究中心,南华大学，药学与生物科学学院,湖南中医药大学，干细胞中药调控与应用研究室;中国－卢森堡中医药合作研究中心

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( 31371161, 81173047)，湖南省自然科学基金(2015JJ6077, 2014JJ1024)，湖南省“十二五”药学重点学科项目( 2011年)，南华大学“十二五”科技创新团队项目


Research: PCSK9/LDLR Pathway Mediates Curcumin Trinicotinate Promoting Lipid Uptake of HepG2
Author:
Affiliation:

College of pharmacy and Biological Sciences, University of South China, Hengyang 421001, China,Division of Stem Cell Regulation and Application,State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan(incubation), Hunan University of Chinese Medicine,Division of Stem Cell Regulation and Application,State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan(incubation), Hunan University of Chinese Medicine;Sino-Luxembourg Cooperative Research Centre for Chinese Medicine,College of pharmacy and Biological Sciences, University of South China,Division of Stem Cell Regulation and Application,State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan(incubation), Hunan University of Chinese Medicine,College of pharmacy and Biological Sciences, University of South China,Division of Stem Cell Regulation and Application,State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan(incubation), Hunan University of Chinese Medicine,College of pharmacy and Biological Sciences, University of South China,Division of Stem Cell Regulation and Application,State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan(incubation), Hunan University of Chinese Medicine;Sino-Luxembourg Cooperative Research Centre for Chinese Medicine

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China (31371161, 81173047), Natural Science Foundation of Hunan Province (2015JJ6077, 2014JJ1024), The Construct Program of the Pharmaceutical Science Key Discipline in Hunan Province and the Innovation Team in University of South China

  • 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:

    为研究PCSK9/LDLR通路介导姜黄素烟酸酯(CurTn)降低血浆低密度脂蛋白胆固醇(LDL-C)，减少动脉内膜下脂质沉积的分子机制，用5、10、15 μmo/L姜黄素烟酸酯与25 mg/L LDL共孵育HepG2细胞24 h，分别采用油红O染色、胆固醇荧光定量试剂盒、DiI-LDL摄取检测细胞内胆固醇含量及LDL摄取情况，用逆转录定量聚合酶链反应(RT-Q-PCR)检测LDLR及SREBP2的mRNA表达，蛋白质印迹检测LDLR、SREBP2及PCSK9蛋白表达．随姜黄素烟酸酯作用浓度的增高细胞内脂滴显著增多，细胞内游离胆固醇(FC)、总胆固醇(TC)含量增高，细胞内胆固醇摄取增多；RT-Q-PCR和蛋白质印迹检测发现，与对照组(Control)比较，5、10、15 μmo/L 姜黄素烟酸酯处理组LDLR 蛋白表达增高，SREBP2 mRNA表达水平升高，PCSK9蛋白表达降低，但对LDLR mRNA及SREBP2 蛋白表达无影响．结果表明：姜黄素烟酸酯通过降低PCSK9、减少LDLR降解、升高LDLR蛋白表达，促进HepG2细胞胆摄取胆固醇．初步说明CurTn可能通过抑制PCSK9介导LDLR溶酶体降解，促进肝脏清除血浆LDL-C水平．

    Abstract:

    Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for the atherosclerotic cardiovascular disease (ASCVD). Over 70% of circulating LDL-C is metabolized by binding hepatic LDL receptor (LDLR). Therefore, elevation of LDLR expression would reduce the progression of ASVCD. In order to study the molecular mechanism of Curcumin Nieotinate (CurTn) reducing lipid deposition of arterial intima by lowering plasma LDL-C, HepG2 cells were treated with 5, 10, 15 μmol/L CurTn co-incubated with 25 mg/L LDL for 24 h. Cellular lipid was detected by oil red O staining. Cholesterol content was detected by cholesterol quantitative fluorometric kit. LDL uptake was visualized by DiI-LDL and Hoechst33342. The mRNA expression of LDLR and SREBP2 was analyzed by quantitative Real-time PCR (RT-Q-PCR) and protein expression of LDLR, SREBP2 and PCSK9 by Western blotting. Oil Red O staining showed that lipid droplets increased significantly in 10, 15 μmol/L CurTn groups. The content of Cholesterol and DiI-LDL uptake were higher in 10, 15 μmol/L CurTn groups than in control group. RT-Q-PCR and Western blotting showed that CurTn increased LDLR protein expression and decreased PCSK9 protein expression, although CurTn also increased SREBP2 mRNA expression. CurTn had no effect on LDLR mRNA expression in HepG2 cells. These results suggest that PCSK9/LDLR pathway may play a key role in lowering serum LDL-C and attenuating ASCVD risk by CurTn.

    参考文献
    相似文献
    引证文献
引用本文

张彩平,孙少卫,龚勇珍,欧露,林丽美,郑兴,庹勤慧,雷小勇,廖端芳. 研究: PCSK9/LDLR通路介导姜黄素烟酸酯促进HepG2摄取脂质[J].生物化学与生物物理进展,2015,42(9):825-832

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:2015-04-23
  • 最后修改日期:2015-06-30
  • 接受日期:2015-07-03
  • 在线发布日期: 2015-09-22
  • 出版日期: 2015-09-20
  • 扫码关注

生物化学与生物物理进展 ® 2024 版权所有 ICP:京ICP备05023138号-1    京公网安备 11010502031771号