α-Tocopherol disturbs macrophage LXRα regulation of ABCA1/G1 and cholesterol handling
- 作者：Sabine Rode ; Tina Rubic ; Reinhard L. Lorenz
- 关键词：
//www.sciencedirect.com/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0">-Tocopherol ; ABCA1 ; ABCG1 ; CD36 ; LXR
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：9 May 2008
- 卷：369
- 期：3
- 页码：868-872
- 文件大小：1144 K
摘要
Based on the oxidation hypothesis high doses of 
-tocopherol have been advocated to prevent atherosclerosis, but clinical trials failed to demonstrate a benefit. As specific oxylipids activate PPARγ and LXR, master regulators of lipid metabolism and cholesterol exporters, we hypothesized, that high dose -tocopherol might interfere with reverse cholesterol transport out of the vessel wall. Human THP-1 cells, a foam cell model, were preincubated with -tocopherol or carrier before exposure to oxidized LDL, delipidated HDL or control buffer. Specific mRNAs were quantified by real-time RT-PCR, LXR activation by a reporter gene assay and cellular cholesterol homeostasis by oxLDL and dHDL facilitated uptake and efflux assays. -Tocopherol significantly reduced baseline expression and stimulation by oxLDL of LXR activity, CD36, ABCA1, and ABCG1. -Tocopherol also reversed the suppression of CD36 and ABCA1 by dHDL. Thus -Tocopherol compromises cellular lipid scavenging and channelling of cholesterol into reverse transport out of the vessel wall.
-tocopherol have been advocated to prevent atherosclerosis, but clinical trials failed to demonstrate a benefit. As specific oxylipids activate PPARγ and LXR, master regulators of lipid metabolism and cholesterol exporters, we hypothesized, that high dose -tocopherol might interfere with reverse cholesterol transport out of the vessel wall. Human THP-1 cells, a foam cell model, were preincubated with -tocopherol or carrier before exposure to oxidized LDL, delipidated HDL or control buffer. Specific mRNAs were quantified by real-time RT-PCR, LXR activation by a reporter gene assay and cellular cholesterol homeostasis by oxLDL and dHDL facilitated uptake and efflux assays. -Tocopherol significantly reduced baseline expression and stimulation by oxLDL of LXR activity, CD36, ABCA1, and ABCG1. -Tocopherol also reversed the suppression of CD36 and ABCA1 by dHDL. Thus -Tocopherol compromises cellular lipid scavenging and channelling of cholesterol into reverse transport out of the vessel wall.