Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone
文献类型：期刊论文
| 作者 | Yang, L; Yang, JB; Chen, J; Yu, GY; Zhou, P; Lei, L; Wang, ZZ; Chang, CCY; Yang, XY; Chang, TY |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2004 |
| 卷号 | 14期号:4页码:315-323 |
| 关键词 | ACAT dexamethasone macrophage cholesteryl ester gene promoter |
| 通讯作者 | Chang, TY (reprint author), Dartmouth Coll Sch Med, Dept Biochem, Lebanon, NH 03756 USA.,Ta.Yuan.Chang@dartmouth.edu ; blli@sibs.ac.cn |
| 英文摘要 | In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | COA-CHOLESTEROL ACYLTRANSFERASE-1 ; LOW-DENSITY-LIPOPROTEIN ; ACYL-COENZYME ; GLUCOCORTICOID-RECEPTOR ; MESSENGER-RNA ; TRANSCRIPTIONAL ACTIVATION ; INTERFERON-GAMMA ; IN-VIVO ; ATHEROSCLEROSIS ; MECHANISM |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000223839200006 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2067]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Yang, L,Yang, JB,Chen, J,et al. Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone[J]. CELL RESEARCH,2004,14(4):315-323. |
| APA | Yang, L.,Yang, JB.,Chen, J.,Yu, GY.,Zhou, P.,...&Li, BL.(2004).Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone.CELL RESEARCH,14(4),315-323. |
| MLA | Yang, L,et al."Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone".CELL RESEARCH 14.4(2004):315-323. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。