THP-1源性巨噬细胞泡沫化过程中肝X受体-α乙酰化修饰改变与SIRT1有关
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湖南省自然科学基金(07JJ6162)项目;衡阳市科技局基础研究计划项目(2008KJ002,2008KJ003)


The Level of LXR-α Acetylation During THP-1 Macrophages Foam-cell Formation
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    摘要:

    目的为研究THP-1源性巨噬细胞泡沫化过程中,SIRT1与肝X受体-α是否发生相互作用、肝X受体-α的乙酰化修饰如何改变及其与细胞内胆固醇含量的关系。方法采用体外培养的THP-1 细胞构建泡沫细胞模型,高效液相色谱法检测细胞内胆固醇含量的变化,免疫共沉淀检测肝X受体-α与SIRT1是否结合,免疫印迹法检测肝X受体-α的乙酰化修饰改变及SIRT1的表达改变。结果在氧化低密度脂蛋白诱导细胞分化12、24 h和48 h后,细胞内胆固醇含量增加,SIRT1与肝X受体-α共沉降,去乙酰化的肝X受体-α蛋白水平升高,SIRT1蛋白的表达增加。结论THP-1源性泡沫细胞形成过程中,肝X受体-α与SIRT1存在相互作用,肝X受体-α的乙酰化修饰逐渐降低,其机制与SIRT1的水平升高有关。

    Abstract:

    AimTo explore whether SIRT1 interacts with liver X receptor-α, the level of liver X receptor-α acetylation and the relationship between liver X receptor-α acetylation and intracellular cholesterol content during THP-1 macrophages foam-cell formation.MethodsTHP-1 macrophages were used to build foam-cell model, the changes of intracellular cholesterol content was detected by high performance liquid chromatography, the level of liver X receptor-α acetylation, the level of SIRT1 expression, and the interaction between liver X receptor-α and SIRT1 were detected by western blot and co-immunoprecipitation respectively.Results After oxidized low-density lipoprotein treated for 12 h, 24 h, 48 h, the cellular cholesterol content of THP-1 macrophages cell was increased gradually, SIRT1 interact with liver X receptor-α, liver X receptor-α acetylation decreased, whereas SIRT1 expression increased.ConclusionDuring THP-1 macrophages foam-cell formation, decreased level of acetylated liver X receptor-α was related to up-regulated expression of SIRT1.

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张弛,黄靓,屈顺林,韦星,唐志晗,佘美华. THP-1源性巨噬细胞泡沫化过程中肝X受体-α乙酰化修饰改变与SIRT1有关[J].中国动脉硬化杂志,2010,18(1):25~28.

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  • 收稿日期:2009-10-30
  • 最后修改日期:2010-01-12
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