期刊文献+

PCSK9及IDOL在姜黄素促进HepG2细胞摄取LDL-C中的作用 被引量:7

Role of PCSK9 and IDOL in curcumin accelerating LDL-C uptake in Hep G2 cells
在线阅读 下载PDF
导出
摘要 目的从分子水平探讨姜黄素的降脂机制,为姜黄素作为降脂药物的临床开发提供科学依据。方法本研究运用油红O染色、酶法测定细胞内胆固醇含量,荧光染色检测细胞胆固醇摄取,RT-Q-PCR及Western blot检测姜黄素对HepG2细胞内胆固醇代谢相关因子在RNA和蛋白水平的表达。结果姜黄素组的HepG2细胞内红色脂滴明显增多,且TC及FC含量增高。Di I标记LDL,姜黄素组HepG2细胞橙红色荧光高于对照组。姜黄素能升高SREBP2和LDLR的mRNA和蛋白水平的表达;降低PCSK9蛋白成熟体及IDOL蛋白表达。结论姜黄素可能通过下调PCSK9及IDOL的表达,进而减少LDLR降解,促进HepG2细胞摄取LDL-C。 Aim To explore the lipid-lowering mechanisms of curcumin from the molecular levels and provide scientific basis for clinical development of lipidlowering drugs. Methods Using oil red O staining and enzymic to determinate the levels of cholesterol in HepG2 cells. Moreover,uptaking of Di I-LDL was also measured. The expressions of mRNA and protein were detected by RT-Q-PCR and Western blot. Results The red lipid droplets and the levels of TC and FC significantly increased in HepG2 cells after treated with curcumin. The orange red fluorescence was higher than that of control. Curcumin could promote the expression levels of mRNA and protein of SREBP2 and LDLR,what's more,curcumin could reduce the expression of the mature PCSK9 level and IDOL protein. Conclusion Curcumin accelerates LDL-C uptake probably via downregulating the expression of PCSK9 and IDOL in HepG2 cells.
出处 《中国药理学通报》 CAS CSCD 北大核心 2015年第9期1286-1291,共6页 Chinese Pharmacological Bulletin
基金 湖南省科技厅项目(No 2015SK2038) 湖南省卫生计生委项目(No B2015-49) 湖南省高层次卫生人才"225"工程项目基金 湖南省自然科学基金(No 2014JJ3104) 南华大学研究生科研创新项目(No 2013XCX20) 南华大学"十二五"科技创新团队基金 南华大学留学回国人员启动基金(No 2013XQD52) 湖南省大学生研究性学习和创新性实验计划项目资助(No 2015-230)
关键词 姜黄素 低密度脂蛋白受体 前蛋白转化酶枯草杆菌蛋白酶9型 诱导低密度脂蛋白受体降解蛋白 固醇调节元件结合蛋白2 3-羟基-3-甲基-戊二酰辅酶A还原酶 curcumin low density lipoprotein choles-terol receptor proprotein convertase subtilisin / kexin type 9 inducible degrader of low-densitylipoprotein re-ceptor sterol regulatory element binding protein 2 ac-tivation of 3-hydroxy-3-methylglutaryl coenzyme A re-ductase
  • 相关文献

参考文献15

  • 1Bhattacharya B S,Sweby P K,Minihane A M,et al.A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway[J].J Theor Biol,2014,349:150-62.
  • 2张锐,张绍芬.低密度脂蛋白受体及其调节机制研究进展[J].国外医学(老年医学分册),2009,30(1):29-33. 被引量:16
  • 3Zelcer N,Hong C,Boyadjian R,et al.LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor[J].Science,2009,325(5936):100-4.
  • 4Watanabe Y,Suzuki S,Nishimura H,et al.Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies:an observational study in Japan[J].Medicine,2015,94(4):e416.
  • 5Nakagami H,Koriyama H,Morishita R.Therapeutic vaccines for hypertension and dyslipidemia[J].Int Heart J,2014,55(2):96-100.
  • 6周中运,范春雷,窦晓兵,胡林峰,钱颖.姜黄素对人正常肝细胞角蛋白1和内质网蛋白19表达的影响[J].中国药理学通报,2013,29(5):700-703. 被引量:1
  • 7Miao J,Haas J T,Manthena P,et al.Hepatic insulin receptor deficiency impairs the SREBP-2 response to feeding and statins[J].J Lipid Res,2014,55(4):659-67.
  • 8Tai M H,Chen P K,Chen P Y,et al.Curcumin enhances cell-surface LDLR level and promotes LDL uptake through downregulation of PCSK9 gene expression in HepG2 cells[J].Mol Nutr Food Res,2014,58(11):2133-45.
  • 9Kohno T.Report of the american heart association(AHA)scientific sessions 2014[J].Chicago Circ J,2015,79(1):34-40.
  • 10胡大一.降低密度脂蛋白胆固醇是硬道理[J].中华心血管病杂志,2015,43(1):3-4. 被引量:28

二级参考文献36

  • 1葛喜珍,田平芳,林强,霍清.大豆异黄酮对卵巢切除大鼠低密度脂蛋白受体(LDLR)mRNA表达的影响[J].中药材,2006,29(4):349-351. 被引量:6
  • 2钱颖,范春雷,窦晓兵,胡林峰,沃兴德.姜黄素对293细胞固醇调控报告系统的作用[J].中国药理学通报,2006,22(7):828-830. 被引量:11
  • 3窦晓兵,沃兴德,范春雷,俞颖,钱颖,黄小黎,凌霞.姜黄素对人肝细胞HepG2中低密度脂蛋白受体基因表达影响的研究[J].中国药学杂志,2007,42(8):572-575. 被引量:9
  • 4Liu J, Streiff R, Zhang YL et al. Novel mechanism of transcriptional activation of hepatic LDL receptor by oncostatin M. J Lipid Res, 1997; 38:2035 -2048
  • 5Liu J, Ahlborn TE, Briggs MR et al. Identification of a novel sterol - independent regulatory element in the human low density lipoprotein receptor promoter. J Biol Chem, 2000; 275 : 5214 -5221
  • 6Li C, Kraemer FB, Ahlborn TE et al. Induction of low density lipoprotein receptor (LDLR) transcription by oncostatin M is mediated by the extracelhlar signal - regulated kinase signaling pathway and the repeat 3 element of the LDLR promoter. J Biol Chem, 1999 ; 274 : 6747 - 6753
  • 7Kong W, Abidi P, Kraemer FB et al. In vivo activities of cytokine oncostatin M in the regulation of plasma lipid levels. J Lipid Res, 2005; 46:1163 -1171
  • 8Mehta KD. Role of mitogen- activated protein kinases and protein kinase C in regulating low - density lipoprotein receptor expression. Gene Expression, 2002; 10:153 -164
  • 9Nakahara M, Fujii H, Maloney PR et al. Bile acids enhance low density lipoprotein receptor gene expression via a MAPK cascade - mediated stabilization of mRNA. J Biol Chem, 2002; 277:37229 - 37234
  • 10Kong W, Wei J, Abidi Pet al. Berberine is a novel cholesterol- lowering drug working through a unique mechanism distinct form statins. Nat Med, 2004; 10:1344 -1351

共引文献42

同被引文献42

引证文献7

二级引证文献26

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部