ox-LDL经由LOX-1受体对PPARγ-LXRα-ABCA1通路激活的作用研究  

Ox-LDL activate PPARγ-LXRα-ABCA1 to transcript by LOX-1 receptor

作　　者：余承洁 李敬达 修志龙[2] 刘庆平[1] YU Cheng-Jie LI Jing-Da XIU Zhi-Long LIU Qing-Pingl(Key Laboratory of Glucolipid Metabolism in Liaoning Province ＆ College of Life Science and Technology, Dalian Universi- ty, Dalian, Liaoning 116600, China College of Life Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, China)

机构地区：[1]辽宁省糖脂代谢重点实验室大连大学生命科学与技术学院,辽宁省大连市116600 [2]大连理工大学生命科学与技术学院,辽宁省大连市116024

出　　处：《中国动脉硬化杂志》2017年第10期978-984,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81270361)

摘　　要：目的探讨氧化型低密度脂蛋白(ox-LDL)经由血凝素样氧化型低密度脂蛋白受体1(LOX-1)受体对PPARγ-LXRα-ABCA1通路激活的作用。方法浓度梯度ox-LDL(0~40 mg/L,12 h)刺激J774A.1巨噬细胞,检测LXRα、ABCA1的表达。构建293T细胞LOX-1过表达的PPARγ双荧光素酶报告基因系统,激光共聚焦及Western blot检测LOX-1的分布与表达,双荧光素酶报告基因系统检测PPARγ的转录活化情况。对J774A.1巨噬细胞分别进行LOX-1 siRNA和PPARγsiRNA沉默,ox-LDL(30 mg/L,12 h)孵育后检测LXRα、ABCA1蛋白的表达。结果ox-LDL可显著上调J774A.1细胞LXRα和ABCA1的表达(P<0.01,n=3)。LOX-1过表达的PPARγ双荧光素酶报告基因系统检测显示ox-LDL能够通过LOX-1增加PPARγ的转录活性;对J774A.1巨噬细胞分别进行LOX-1siRNA、PPARγsiRNA沉默后发现,LXRα和ABCA1的表达均显著降低(P<0.01,n=3)。结论 ox-LDL可通过LOX-1受体激活PPARγ转录活性,从而上调LXRα、ABCA1蛋白表达,完成PPARγ-LXRα-ABCA1信号通路的激活。Aim To investigate the effect of oxidized low density lipoprotein （ox-LDL） on activation of PPARγ- LXRα-ABCA1 pathway via lectin-like oxidized low density lipoprotein receptor-1 （LOX-1） receptor. Methods The expression of liver X receptor α（LXRα） and ABCA 1 was detected by stimulating J774A. 1 macrophages with concentration gradient ox-LDL （0- 40 mg/L, 12 h）, the expression of LOX-1 was detected by laser confocal microscopy and Western blot, the transcriptional activation of peroxisome proliferators-activated receptor γ （PPARγ） was detected by double lucif- erase reporter gene, the expression of LXRα and ATP-binding cassette transporter A1 （ABCA1） protein was detected after incubation with J774A.1 macrophages by LOX-1 siRNA and PPARγsiRNA silencing, ox-LDL （30 mg/L,12 h）. Re- suits Ox-LDL significantly up-regulated the expression of LXRα and ABCA1 in J774A. 1 cells （ significantly different from the cell untreated by ox-LDL as control, P〈0.01, n= 3）. LOX-1 overexpression of PPARγ double luciferase reporter gene system showed that ox-LDL increased the transcriptional activity of PPARγ by LOX-1. LOX-1 siRNA and PPARγ siRNA were treated with J774A. 1 macrophages, respectively, and LXRα and ABCA1 were expressed （significantly different from the cell untreated by siRNA as control, P〈0.01, n = 3）. Conclusion Ox-LDL activates PPARγ tran- scriptional activity by LOX-1 receptor, thereby upregulating LXRα and ABCA1 protein expression and activating PPARγ-LXRα-ABCA1 signal pathway.

关 键 词：血凝素样氧化型低密度脂蛋白受体1 氧化型低密度脂蛋白 过氧化体增殖物激活型受体Γ 肝X受体Α 三磷酸腺苷结合盒转运体Al 

分 类 号：Q75[生物学—分子生物学]