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Effect of insulin on transcriptional activity of human ACAT1 gene P1 and P7 promoters in THP-1 cells and THP-1-derived macrophages
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF PATHOPHYSIOLOGY
- Issue:
- 11
- DOI:
- 10.3969/j.issn.1000-4718.2012.11.007
- Key Word:
- 胰岛素;酰基辅酶A;胆固醇酰基转移酶1;动脉粥样硬化;启动子;转录活性
Abstract： 目的:研究胰岛素对人单核/巨噬细胞酰基辅酶A:胆固醇酰基转移酶1(acyl coenzyme A:cholesterol acyltransferase 1,ACAT1)基因P1和P7启动子的活性及其转录产物表达的影响,从而探讨它们在胰岛素调控ACAT1基因表达中的作用.方法:将人ACAT1基因P1和P7启动子调控的报告基因载体pGL3E-P1和pGL3E-P7 瞬时转染入体外培养人THP-1 单核细胞系,给予不同剂量的胰岛素处理,通过双萤光素酶报告系统检测P1和P7启动子的活性.体外培养THP-1细胞和由佛波脂诱导分化的巨噬细胞,同样用不同剂量的胰岛素干预24 h,应用逆转录聚合酶链反应(RT-PCR)检测THP-1细胞ACAT1 基因P1和P7启动子转录产物表达,用SYBR GreenⅠ实时定量RT-PCR方法检测THP-1细胞和诱导分化的巨噬细胞ACAT1 mRNA的表达.结果:不同剂量胰岛素处理的人THP-1细胞,与对照组相比,ACAT1基因 P1启动子的活性及其转录产物量均显著增强,并随胰岛素剂量的增加而升高.应用实时定量RT-PCR方法检测ACAT1 mRNA的表达与上述结果相一致.结论:胰岛素可通过激活人单核/巨噬细胞 ACAT1 基因 P1启动子上调ACAT1 mRNA的表达,其作用呈剂量依赖性.
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