Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell for

Enhancement of human ACAT1 gene expression to

promote the macrophage-derived foam cell

formation by dexamethasone

Li YANG;Ta Yuan CHANG;Bo Liang LI;Jin Bo YANG;Jia CHEN;Guang Yao YU;Pei ZHOU;Lei LEI;Zhen Zhen WANG;Catherine CY CHANG;XinYing YANG

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2004(014)004

【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-l-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 ACAT1gene 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.

【总页数】9页(315-323)

【关键词】ACAT;dexamethasone;macrophage;cholesteryl ester;gene promoter

【作者】Li YANG;Ta Yuan CHANG;Bo Liang LI;Jin Bo YANG;Jia CHEN;Guang Yao YU;Pei ZHOU;Lei LEI;Zhen Zhen WANG;Catherine CY CHANG;XinYing YANG

【作者单位】State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State

Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang

Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China;Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03756, USA;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China 【正文语种】中文 【中图分类】Q2 【文献来源】

https://www.zhangqiaokeyan.com/academic-journal-cn_cell-research-english_thesis/0201255254017.html 【相关文献】

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