不对称二甲基精氨酸上调THP-1来源的巨噬细胞和泡沫细胞内胆固醇酞基转移酶-1的表达

目的 观察不对称二甲基精氨酸(ADMA)对单核细胞THP-1来源的巨噬细胞和泡沫细胞中胆固醇酞基转移酶-1(ACAT-1)的表达及胆固醇含量的影响.方法 分别采用RT-PCR和Westem blot技术检测ACAT-1mRNA和蛋白表达水平.采用酶偶联比色法检测细胞内胆固醇含量.结果 不同浓度的ADMA (0,3.75,7.5,15,or30 μmol/L)对THP-1来源的巨噬细胞和泡沫细胞作用不同时间(6 12,24h)后,巨噬细胞和泡沫细胞内ACAT-1mRNA和蛋白的表达明显上调,细胞内总胆固醇的含量明显升高.结论 ADMA在巨噬细胞形成泡沫细胞过程中可能发挥了重要作用.抑制巨噬细胞和泡沫细胞内ACAT-1可能成为治疗动脉粥样硬化的潜在靶点.

Abstract：

Abstract:Objective To investigate the effects of asymmetric dimethylarginine(ADMA)on ACAT-I expression and cholesterol content in THP-1-derived macrophages and foam cells. Methods THP-1 cells were induced to differentiate into macrophages and further into foam ceIls.The macrophages and foam cells were exposed to different concentrations(0,3.75,7.5,15,and 30umol/K)of ADMA for varying time lengths(6,12,and 24 h),and the changes in ACAT-1 mRNA and protein levels in the cells were measured with RT-PCR and Western blotting.The cellular cholesterol content Was measured with enzyme-linked colorimetry assay.Results In THP-1-derived macrophages and foam cells,the expression levels of ACAT-1 mRNA and protein and cellular cholesterol content increased significantly in response to ADMA treatment in a time- and concentration-dependent manner. Conclusion ADMA may play all important role in inducing foam cell formation from macrophages. ACAT-1 inhibition targeting the macrophages and foam cells may serve as a potential therapeutic target IN the treatment of atherosclerosis.

Asymmetric dimethylarginine upregulates the expression of ACAT-1 in THP-1 macrophage-derived foam cells

Abstract:Objective To investigate the effects of asymmetric dimethylarginine(ADMA)on ACAT-I expression and cholesterol content in THP-1-derived macrophages and foam cells. Methods THP-1 cells were induced to differentiate into macrophages and further into foam ceIls.The macrophages and foam cells were exposed to different concentrations(0,3.75,7.5,15,and 30umol/K)of ADMA for varying time lengths(6,12,and 24 h),and the changes in ACAT-1 mRNA and protein levels in the cells were measured with RT-PCR and Western blotting.The cellular cholesterol content Was measured with enzyme-linked colorimetry assay.Results In THP-1-derived macrophages and foam cells,the expression levels of ACAT-1 mRNA and protein and cellular cholesterol content increased significantly in response to ADMA treatment in a time- and concentration-dependent manner. Conclusion ADMA may play all important role in inducing foam cell formation from macrophages. ACAT-1 inhibition targeting the macrophages and foam cells may serve as a potential therapeutic target IN the treatment of atherosclerosis.