文章摘要
方明明,吴晓燕,戚晓红.缺氧状态下去乙酰化酶SIRT1对MHCⅡ的反式激活因子的调控机制研究[J].南京医科大学学报,2011,(12):1772~1776
缺氧状态下去乙酰化酶SIRT1对MHCⅡ的反式激活因子的调控机制研究
The regulatory effect of SIRT1 on CⅡTA under hypoxia
投稿时间:2011-08-27  
DOI:10.7655
中文关键词: 缺氧  SIRT1  免疫功能  MHC II
英文关键词: hypoxia  SIRT1  immune function  MHC Ⅱ
基金项目:江苏省卫生厅课题资助(H200965);南京医科大学青年教师培养基金(jx1011780111);江苏省高校自然科学研究计划项目(08KJB310006)
作者单位
方明明 江苏建康职业学院医学护理系,江苏 南京 210029 
吴晓燕 南京医科大学基础医学国家级实验教学示范中心,江苏 南京 210029 
戚晓红 南京医科大学基础医学国家级实验教学示范中心,江苏 南京 210029 
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中文摘要:
      目的:探讨缺氧对SIRT1表达和活性的影响,及SIRT1对人体免疫功能的调节机制?方法:将人的原代外周血巨噬细胞在常氧和缺氧(1% O2)条件下培养,用Western blot方法检测细胞内SIRT1的蛋白表达变化,Real-time PCR检测SIRT1?NAMPT?HLA-DR?琢的mRNA水平,检测SIRT1的酶活性及NAD+/NADH的值?结果:SIRT1蛋白表达随缺氧时间的延长先降低后升高,缺氧12 h蛋白下降最明显,24?36 h后回升,但表达量仍低于常氧;缺氧12 h后,SIRT1?NAMPT的mRNA水平与常氧组比较明显降低(P < 0.05);SIRT1的酶活性和NAD+/NADH的值显著低于常氧组(P < 0.05);SIRT1激动剂白藜芦醇能够逆转缺氧诱导的HLA-DR?琢的mRNA表达下调?结论:缺氧通过调节巨噬细胞中SIRT1 的mRNA水平?蛋白表达及酶活性,使得依赖Ⅱ类反式激活因子(classⅡ trans-activator,CⅡTA)的HLA-DR?琢表达下降,提示SIRT1可能是一个新的值得关注的免疫调节相关蛋白?
英文摘要:
      Objective: To investigate the effects of hypoxia on the expression and activity of SIRT1 and its regulatory mechanisms on human immune function. Methods: Human primary peripheral blood monocytes(HPBMs) were cultured in vitro under normal oxygen and hypoxia(1% O2) conditions. The protein expression of SIRT1 was detected by Western blot. Real-time PCR was performed to examine the mRNA levels of SIRT1,NAMPT and HLA-DR?琢. Activity assay kits were used to detect the activity of SIRT1 and value of NAD+/NADH. Results: SIRT1 protein level was inhibited with peak inhibition occurring at 12 h post exposure to hypoxia. The mRNA levels of SIRT1 and NAMPT in cells cultured in hypoxia were significantly lower than that cultured in normal oxygen(P < 0.05). In addition,the enzyme activity of SIRT1 and the value of NAD+/NADH were also significantly decreased (P < 0.05). Resveratrol, which is the agonist of SIRT1,rescued the decreased expression of HLA-DR?琢 induced by hypoxia. Conclusion: The CⅡTA-dependent HLA-DR?琢 expression was decreased,and accompanied with a decrease in the expression and enzyme activity of SIRT1 in macrophages exposed to hypoxia. These results revealed that SIRT1 may play a critical role in regulating adaptive immunity.
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