ox-LDL通过NAD依赖性脱乙酰酶SIRT1抑制MHC Ⅱ反式激活蛋白的转录活性
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国家自然科学基金青年资助(31200645);南京医科大学科技发展基金项目(2011NJMU268)


Ox-LDL inhibits the transcriptional activity of trans-activating pratein MHC II by NAD dependent of the deacetylase SIRT1
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    摘要:

    目的:探讨氧化低密度脂蛋白(ox-LDL)对NAD依赖性脱乙酰酶(NAD-dependent deacetylase)SIRT1表达的影响,及SIRT1调节人体适应性免疫应答过程中的机制-方法:体外培养人的原代外周血单核细胞,经集落刺激因子(GM-CSF)刺激分化7 d形成巨噬细胞,将分化良好的巨噬细胞分别用不同浓度ox-LDL(0~120 μg/ml)培养48 h-应用Western blot方法检测细胞内SIRT1的蛋白表达变化,Real-time PCR检测SIRT1-HLA-DRα的mRNA水平-结果:SIRT1蛋白表达随ox-LDL浓度的升高而降低;ox-LDL处理后,SIRT1的mRNA水平与对照组比较显著降低(P < 0.05);SIRT1激动剂白藜芦醇能够逆转ox-LDL诱导的HLA-DRα启动子的活性下调-结论:ox-LDL通过调节巨噬细胞中SIRT1的蛋白表达和mRNA水平,使依赖MHC Ⅱ反式激活蛋白(class II trans-activator,CIITA)的HLA-DRα启动子活性下降,提示脱乙酰酶SIRT1可能是临床上干预动脉粥样硬化的潜在靶位点-

    Abstract:

    Objective:To investigate the effects of oxidized low-density lipoprotein(ox-LDL) on the expression and activity of NAD-dependent deacetylase SIRT1 and its regulatory mechanisms on human adaptive immune function. Methods:Human primary peripheral blood monocytes were induced by human macrophage colony stimulating factor GM-CSF for 7 days in vitro. Well differentiated macrophages were treated with different concentrations(0~120 μg/ml) of ox-LDL for 48 h. The protein expression of SIRT1 was detected by Western blot. Real-time PCR was performed to examine the SIRT1 and HLA-DRα mRNA. Results:The protein expression of SIRT1 was decreased by ox-LDL in a concentration-dependent manner. The mRNA of SIRT1 treated by ox-LDL was significantly lower than that of the control group(P < 0.05).Resveratrol,which is the agonist of SIRT1,rescued the decreased expression of HLA-DRα induced by ox-LDL. Conclusion:The CIITA-dependent HLA-DRα promoter activity was decreased when treated with ox-LDL,which was induced by the change of mRNA and protein expression of SIRT1 in macrophage. Therefore,deacetylase SIRT1 may provide potential target for the treatment of atherosclerosis.

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方明明,宋鸣子,周红,吴晓燕. ox-LDL通过NAD依赖性脱乙酰酶SIRT1抑制MHC Ⅱ反式激活蛋白的转录活性[J].南京医科大学学报(自然科学版),2014,(4):405-409

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  • 收稿日期:2013-12-03
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  • 在线发布日期: 2014-04-18
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