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酰基转移酶-1的表达(英文)  

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

作　　者：朱振东[1,2] 贾俊琴[1] 张旋[1] 王庸晋[3] 王殿华[1] 

机构地区：[1]昆明医学院药学院暨云南省天然药物药理重点实验室,云南昆明650031 [2]昆明医学院附属昆华医院干疗科,云南昆明650233 [3]长治医学院附属和平医院心血管病研究所,山西长治046000

出　　处：《南方医科大学学报》2010年第12期2613-2618,共6页Journal of Southern Medical University

基　　金：Supported by National Natural Science Foundation of China(30840043)~~

摘　　要：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酰基转移酶-1(ACAT-1)的表达及胆固醇含量的影响。方法分别采用RT-PCR和Western 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,or30μmol/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。Objective To investigate the effects of asymmetric dimethylarginine （ADMA） on ACAT-1 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 cells. The macrophages and foam cells were exposed to different concentrations （0,3.75,7.5,15,and 30 μmol/L） 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 an 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.

关 键 词：不对称二甲基精氨酸 单核细胞THP-1 巨噬细胞 泡沫细胞 酰基辅酶A 胆固醇酰基转移酶-1 

分 类 号：R543.5[医药卫生—心血管疾病]