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VLDL、β-VLDL诱导巨噬细胞极低密度脂蛋白受体表达上调的信号转导途径探讨

Upregulation of VLDL receptor in macrophages induced by VLDL and β-VLDL via PKC-ERK1/2 signaling pathway

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【作者】 屈伸李映红田俊王燕宗义强冯友梅冯宗忱邓耀祖

【机构】 华中科技大学同济医学院生物化学与分子生物学系

【摘要】 为了研究极低密度脂蛋白受体(very low density lipoprotein receptor,VLDL-R)的主要天然配体VLDL、β-VLDL对巨噬细胞VLDL-R表达调控效应及其信号转导途径,以VLDL、β-VLDL温育小鼠巨噬细胞RAW264.7,检测胞内VLDL—R mRNA的表达变化;构建含VLDL-R5’端转录调控序列的重组质粒pGL4.2VR-luciferase,转染RAW264.7细胞后,检测VLDL、β-VLDL温育对VLDL-R5’端转录调控序列转录活性的影响;采用Western Blot方法检测细胞温育后ERK1/2活性变化;应用各种信号转导途径抑制剂的阻断效应,确定VLDL—R表达调控的信号转导途径。实验结果显示:VLDL、β-VLDL通过PKC-ERK1/2信号转导途径,转录激活VLDL-R表达。

【Abstract】 Very low density lipoprotein receptor (VLDL - R) is thought to participate in the pathogen-esis of atherosclerosis induced by VLDL and β - VLDL The present study was undertaken to elucidate the effects of VLDL andβ - VLDL on VLDL - R expression and its signaling pathway. The study on murine macro phages incubated with VLDL orβ - VLDL showed that both of them increased VLDL - R expression, which was observed at levels of VLDL - R mRNA by RT - PCR analysis and transcriptional regulation of VLDL - R gene promoter - driven luciferase activity. Using Western Blot Assay to detect phosphorylated ERK1/2 protein, we found that VLDL andβ - VLDL stimulated ERK1/2 activity in a PKC - dependent manner. Studies using different protein kinases inhibitors or activators indicated that the effect of VLDL orβ - VLDL - induced VLDL - R expression in macrophages was extremely abolished by an inhibitor of ERK and an inhibitor of PKC. Taken together, our findings reveal that VLDL - orβ - VLDL - induced VLDL - R expression via PKC/ERK1/2 cascades and the effect is linked to transcriptional activation of VLDL - R gene promoter.

  • 【会议录名称】 2004全国血脂分析及其临床应用学术研讨会、第七届全国脂蛋白学术会议论文汇编
  • 【会议名称】2004全国血脂分析及其临床应用学术研讨会、第七届全国脂蛋白学术会议
  • 【会议时间】2004-08
  • 【会议地点】中国银川
  • 【分类号】R543.5
  • 【主办单位】中华医学会检验分会、中国生物化学与分子生物学学会脂蛋白专业委员会
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