| 对氧磷降低RAW264.7巨噬细胞源性泡沫细胞ABCA1表达和胆固醇流出 |
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| 引用本文： | 周寿红,杨旭红,吴树金,陈庚容,刘立英. 对氧磷降低RAW264.7巨噬细胞源性泡沫细胞ABCA1表达和胆固醇流出[J]. 生物化学与生物物理进展, 2010, 37(2): 190-199 |
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| 作者姓名： | 周寿红 杨旭红 吴树金 陈庚容 刘立英 |
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| 作者单位： | 中南大学湘雅医学院药学院药理学教研室;南华大学医学院生理学教研室; |
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| 基金项目： | supported by grants from The National Natural Science Foundation of China(30570754); The Fund of the Department of Education of Hunan Province(08C746); The Fund for Bring New Ideal of Central South University(ZRE52)~~ |
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| 摘 要： | 三磷酸腺苷结合盒转运体A1(ABCA1)是体内胆固醇逆向转运的关键环节.对氧磷是广泛使用的有机磷农药的活性代谢产物.研究发现,对氧磷能增加巨噬细胞中胆固醇的堆积,但具体机制还不清楚.以RAW264.7巨噬细胞源性泡沫细胞为研究对象,观察对氧磷对RAW264.7巨噬细胞源性泡沫细胞ABCA1表达和胆固醇流出的影响并探讨其机制.结果显示,对氧磷以时间和剂量依赖的方式增加RAW264.7巨噬细胞源性泡沫细胞中总胆固醇、游离胆固醇和胆固醇酯水平,降低ABCA1表达和胆固醇流出,同时对氧磷降低细胞中环磷酸腺苷(cAMP)的水平及腺苷酸环化酶(AC)的活性和增加磷酸二酯酶(PDE)的活性,而cAMP的类似物双丁酰环腺苷酸(dBcAMP)能够阻断对氧磷降低ABCA1表达和部分阻断对氧磷降低胆固醇流出,对氧磷导致的cAMP水平的降低也可被AC激动剂福斯高林(Forskolin)和PDE抑制剂3-异丁基-1-甲基黄嘌呤(IBMX)所阻断.以上结果表明,对氧磷通过cAMP信号通路下调RAW264.7巨噬细胞源性泡沫细胞ABCA1的表达,降低细胞内胆固醇流出和增加细胞内胆固醇堆积.
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| 关 键 词： | 对氧磷 三磷酸腺苷结合盒转运体A1 环磷酸腺苷 动脉粥样硬化 逆向胆固醇转运 |
| 收稿时间： | 2009-08-10 |
| 修稿时间： | 2009-11-26 |
Paraoxon down regulates ATP-binding cassette transporter A1 expression and decreases cholesterol efflux through cyclic AMP signaling pathway in RAW 264.7 macrophage-derived foam cells |
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| ZHOU Shou-Hong,YANG Xu-Hong,WU Shu-Jin,CHEN Gen-Grong and LIU Li-Ying. Paraoxon down regulates ATP-binding cassette transporter A1 expression and decreases cholesterol efflux through cyclic AMP signaling pathway in RAW 264.7 macrophage-derived foam cells[J]. Progress In Biochemistry and Biophysics, 2010, 37(2): 190-199 |
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| Authors: | ZHOU Shou-Hong YANG Xu-Hong WU Shu-Jin CHEN Gen-Grong LIU Li-Ying |
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| Affiliation: | ZHOU Shou-Hong1,2),YANG Xu-Hong1),WU Shu-Jin1),CHEN Geng-Rong1),LIU Li-Ying1)(1)Department of Pharmacology,Xiang-Ya Medical College,Central South University,Changsha 410078,China,2) Department of Physiology,School of Medicine,University of South China,Hengyang 421001,China) |
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| Abstract: | ATP-binding Cassette Transporter A1(ABCA1) plays a critical role in the reverse cholesterol transport(RCT).Previous studies showed that paraoxon,the active metabolite of organophosphorus insecticide,increased cholesterol retention in macrophages.However,its underlying mechanisms remain to be elucidated.The effect of paraoxon on ABCA1 expression and ABCA1-dependent cholesterol efflux was investigated,and then the role of cyclic adenosine monophospate(cAMP) signaling pathway in the regulation of ABCA1 express... |
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| Keywords: | paraoxon ABCA1 cAMP atherosclerosis reverse cholesterol transport |
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