| Daxx通过上调caveolin-1的表达介导Ox-LDL诱导巨噬细胞胆固醇蓄积和凋亡 |
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| 引用本文： | 贺庆芝,庹勤慧,曾怀才,朱炳阳,让蔚清,唐小卿,廖端芳. Daxx通过上调caveolin-1的表达介导Ox-LDL诱导巨噬细胞胆固醇蓄积和凋亡[J]. 生物化学与生物物理进展, 2010, 37(8): 881-890 |
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| 作者姓名： | 贺庆芝 庹勤慧 曾怀才 朱炳阳 让蔚清 唐小卿 廖端芳 |
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| 作者单位： | 南华大学药物药理研究所，衡阳 421001;南华大学药物药理研究所，衡阳 421001;南华大学公共卫生学院，衡阳 421001;南华大学药物药理研究所，衡阳 421001;南华大学公共卫生学院，衡阳 421001;南华大学医学院生理教研室，衡阳 421001;南华大学药物药理研究所，衡阳 421001；湖南中医药大学中医分子诊断研究室，长沙 410208 |
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| 基金项目： | 国家自然科学基金资助项目(30572191, 30770868, 30971267, 30971170) |
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| 摘 要： | 为探讨Daxx对氧化型低密度脂蛋白(oxidized low-density lipoprotein，Ox-LDL)诱导巨噬细胞胆固醇蓄积和凋亡的介导作用及其可能的分子机制，用高效液相色谱法检测细胞内胆固醇含量，油红O染色观察细胞内脂滴的形成情况，流式细胞术和吖啶橙/溴化乙锭(AO/EB)染色法研究Ox-LDL对细胞凋亡的影响，Real time RT-PCR检测细胞内Daxx mRNA的表达水平，Western blot检测caveolin-1蛋白的表达，用特异性siRNA沉默Daxx在RAW264.7 细胞中的表达．Ox-LDL上调Daxx mRNA和caveolin-1的表达、增加细胞内胆固醇含量、促使RAW264.7细胞凋亡，用特异性siRNA干扰Daxx在RAW264.7细胞中的表达能降低caveolin-1的表达、减少细胞内胆固醇含量、以及抑制细胞凋亡．上述结果表明，Daxx对Ox-LDL诱导RAW264.7巨噬细胞胆固醇蓄积和凋亡具有介导作用，这一作用可能与Daxx上调caveolin -1的表达有关．
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| 关 键 词： | Daxx，氧化型低密度脂蛋白，巨噬细胞，凋亡，caveolin-1 |
| 收稿时间： | 2010-03-25 |
| 修稿时间： | 2010-05-12 |
Daxx Mediates Oxidized Low-density Lipoprotein-Induced Cholesterol Accumulation and Apoptosis in Macrophages by Upregulating Caveolin-1 Expression |
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| HE Qing-Zhi,TUO Qin-Hui,ZENG Huai-Cai,ZHU Bing-Yang,RANG Wei-Qing,TANG Xiao-Qing and LIAO Duan-Fang. Daxx Mediates Oxidized Low-density Lipoprotein-Induced Cholesterol Accumulation and Apoptosis in Macrophages by Upregulating Caveolin-1 Expression[J]. Progress In Biochemistry and Biophysics, 2010, 37(8): 881-890 |
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| Authors: | HE Qing-Zhi TUO Qin-Hui ZENG Huai-Cai ZHU Bing-Yang RANG Wei-Qing TANG Xiao-Qing LIAO Duan-Fang |
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| Affiliation: | Province Key Laboratory of Pharmacoprotomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China;Province Key Laboratory of Pharmacoprotomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China;School of Public Health, University of South China, Hengyang 421001, China;Province Key Laboratory of Pharmacoprotomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China;School of Public Health, University of South China, Hengyang 421001, China;Department of Physiology, School of Medicine, University of South China, Hengyang 421001, China;Province Key Laboratory of Pharmacoprotomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China;Department of Traditional Chinese Diagnotics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China |
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| Abstract: | To explore whether Daxx mediates oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and apopotosis in macrophage and the underlying molecular mechanisms, intracellular lipid droplets and lipid levels were assayed by oil red O staining and high performance liquid chromatography (HPLC), respectively, the apoptotic effect of RAW264.7 cells induced by Ox-LDL was analyzed by flow cytometric analysis and acridine orange/ethidium bromide (AO/EB) staining, the mRNA expressions of Daxx was quantified by Real time RT- PCR, the protein expression of caveolin-1 was detected by Western-blotting, Daxx-specific small interfering RNA(Daxx siRNA) was transfected to RAW264.7 cell by lipofectamin. Ox-LDL up-regulated the expression of Daxx mRNA, increased the accumulation of intercellular cholesterol in RAW264.7 macrophages, and induced the apoptosis of RAW264.7 macrophages. However, Ox-LDL-induced intercellular cholesterol accumulation and apoptosis in RAW264.7 cells was prevented by Daxx siRNA. Ox-LDL also induced caveolin-1 expression and this effect is significantly suppressed by Daxx siRNA. It can be concluded that Daxx mediates Ox-LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating caveolin-1 expression. These findings provide an important demonstration that Daxx might be associated with the development of atherosclerosis. |
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| Keywords: | Daxx Ox-LDL macrophage apoptosis caveolin-1 |
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