过氧化体增殖物激活型受体γ和δ在高密度脂蛋白介导细胞胆固醇流出中的作用
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The Role of Peroxisome Proliferator-Activated Receptors-gamma and-delta in the Cellular Cholesterol Efflux Mediated by High Density Lipoprotein
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    摘要:

    为探讨过氧化体增殖物激活型受体γ和δ在高密度脂蛋白介导的细胞胆固醇流出中的作用。取新鲜抗凝血浆,用超速离心机进行密度梯度离心,收集密度为1 .0 6 3~1 .2 1 0组分。U937细胞用5 0~4 0 0nmol L反义过氧化体增殖物激活型受体γ和δ预处理细胞1 2h。培养U937细胞与0 .2 8mCi L [3H] 胆固醇乙醇液共孵育2 4h ,15 0 0r min离心1 0min ,收集细胞,PBS漂洗2次,RPMI 1 6 4 0重悬细胞,加HDL继续培养0~4 8h。液体闪烁计数仪测细胞相对放射活性。Westernblot检测过氧化体增殖物激活型受体γ和δ蛋白表达水平。不同浓度HDL处理后细胞胆固醇流出具有明显差异,呈剂量-效应关系。用1 0 0nmol L反义过氧化体增殖物激活型受体γ处理2 4h后,HDL介导的细胞胆固醇流出减少(4 5 78±2 0 6 ) ,与对照组(4 0 2 4±385 )比较差别有显著性。过氧化体增殖物激活型受体γ激动剂ciglitizone预处理后,HDL介导的细胞胆固醇流出增加,用0、2 5、5 0、1 0 0、2 0 0 μmol Lciglitizone处理的放射活性分别为4 371±2 4 3、386 9±2 1 2、346 9±2 0 9、31 5 6±31 5和30 2 0±2 96。反义过氧化体增殖物激活型受体δ处理后,HDL介导的细胞胆固醇流出略有增加,处理浓度达4 0 0nmol L时的放射活性为31 6 4±2 1 3,与对照组(4 1 31±2 79)比较有显著性差异。反义过氧化体增殖物激活型受体γ和δ联合处理的净效应为胆固醇流出减少。过氧化体增殖物反应元件类似序列处理使胆固醇流出明显受阻。HDL处理使过氧化体增殖物激活型受体γ表达水平增加,而过氧化体增殖物激活型受体δ表达水平下调。过氧化体增殖物激活受体γ具有促细胞胆固醇流出的作用;过氧化体增殖物激活型受体δ可能具有阻止细胞胆固醇流出的作用

    Abstract:

    Aim This study examines the relationship between PPAR gamma and delta and cholesterol efflux mediated by high density lipoprotein. Methods Pooled plasma were collected from health human. Component (density 1.063 1.21 g/cm 3) was prepared by density ultracentrifugation. U937 cells were treated by cholesterol for 24 h, cell pellets were washed with PBS, then added RPMI 1640 supplemented with 1% FBS. The cells were treated by the antisense PPAR gamma and delta oligo DNA, PPAR gamma activator ciglitazone, and PPAR responsive element decoy, respectively. The effects of the oligo DNA on efflux of cholesterol was evaluated by relative radioactivity of the cell pellets. PPAR gamma and delta protein expression levels were assayed by Western blot. Results The results demonstrated that HDL promoted cellular cholesterol efflux in dose and time dependent manner reflected by radioactivity of cell pellets. It was also observed an increase in HDL mediated cholesterol efflux associated with a decrease of antisense oligo DNA of PPAR gamma, and an decrease in HDL mediated cholesterol efflux associated with decrease of antisense oligo DNA of PPAR delta, both in a dose dependent manner. PPAR activator ciglitazone stimulated the HDL mediated cholesterol efflux. Treatment with PPAR responsive element decoy inhibited the cholesterol efflux mediated by HDL. Western blot assay demonstrated that PPARgamma protein level was increased, while PPARdelta level decreased by HDL. Conclusion This study suggests that PPAR gamma may improve the cholesterol efflux mediated by HDL, PPAR delta may prevent the HDL mediated cholesterol efflux.

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易光辉,杨永宗,唐朝克,米五平,王燕,危当恒.过氧化体增殖物激活型受体γ和δ在高密度脂蛋白介导细胞胆固醇流出中的作用[J].中国动脉硬化杂志,2003,11(4):325~329.

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  • 收稿日期:2003-01-29
  • 最后修改日期:2003-06-16
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