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激活类法尼醇X核内受体(FXR)可下调载脂蛋白M在HepG2细胞中的表达

Activation of Farnesoid X Receptor Down-regulates Expression of Apolipoprotein M in Cultured HepG2 Cell

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【作者】 张艳刘红彭家和董金瑜王强李良鹏王永超江渝

【Author】 ZHANG Yan 1),LIU Hong 2),PENG Jia-He 1),DONG Jin-Yu 1),WANG Qiang 1),LI Liang-Peng 1),WANG Yong-Chao 1),JIANG Yu 1)( 1)Department of Biochemistry and Molecular Biology,Third Military Medical University,Chongqing 400038,China; 2)Department of Clinical Laboratory,Xinqiao Hospital,Third Military Medical University,Chongqing 400038,China)

【机构】 第三军医大学基础部生物化学与分子生物学教研室第三军医大学附属新桥医院血液科

【摘要】 类法尼醇X核内受体(farnesoid Xreceptor,FXR)和载脂蛋白M(ApoM)在动脉粥样硬化中发挥重要作用.为研究FXR激动剂鹅脱氧胆酸(chenodexycholic acid,CDCA)和拮抗剂Guggulsterones在人肝癌细胞株HepG2和人胎肝细胞株L02中对载脂蛋白M(apolipoprotein M,ApoM)表达的影响.本研究应用逆转录-聚合酶链反应(RT-PCR)法和Western印迹法检测CDCA和CDCA加Guggulsterones处理后HepG2和L02细胞中ApoM的mRNA水平和HepG2细胞中ApoM的蛋白水平.实验结果显示:FXR天然配体CDCA以剂量依赖的方式显著降低HepG2细胞中ApoM分子(mRNA和蛋白水平)的表达,L02细胞中ApoM分子mRNA水平的表达;FXR抑制剂Guggulsterones不仅能明显阻止CDCA对ApoM表达的下调,而且可引起ApoM表达显著增加.本研究提示,FXR抑制剂Guggulsterones在抗动脉粥样硬化过程中可能发挥重要作用.

【Abstract】 Many evidences have shown that FXR and ApoM play important roles in atherosclerosis.In the further studies,the FXR(farnesoid X receptor)agonist chenodexycholic acid(CDCA)and FXR antagonist Guggulsterones affect the expression of apolipoprotein M(ApoM)in human liver carcinoma cell line HepG2 and fetal liver cell L02.HepG2 and L02 cells were treated with FXR agonist CDCA and antagonist Guggulsterones.The mRNA level of ApoM was detected by reverse transcription-polymerase chain reaction(RT-PCR)and protein level of ApoM was examinated by Western blotting.Our study shows that ApoM mRNA and protein level were significantly reduced(P<0.05)in a concentration-dependent manner by FXR agonist CDCA in HepG2 cells.FXR antagonist Guggulsterones not only can significantly interrupt(P<0.05)reduaction of ApoM expression,but also significantly increase(P<0.05)expression of ApoM in HepG2 and L02.The results suggest that FXR antagonist Guggulsterones may play a very important role in antiatherosclerosis.

【基金】 重庆市自然科学基金(No.2007BB5050);第三军医大学留学回国人员启动基金(No.06HG010)联合资助~~
  • 【文献出处】 中国生物化学与分子生物学报 ,Chinese Journal of Biochemistry and Molecular Biology , 编辑部邮箱 ,2009年11期
  • 【分类号】Q25
  • 【被引频次】8
  • 【下载频次】319
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