Overexpression of mitochondrial cholesterol delivery protein, StAR, decreases intracellular lipids and inflammatory factors secretion in macrophages.
Overexpression of mitochondrial cholesterol delivery protein, StAR, decreases intracellular lipids and inflammatory factors secretion in macrophages.
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DOI：
10.1016/j.atherosclerosis.2008.09.006
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发表时间：
2009-05
期刊：
影响因子：
5.3
通讯作者：
Yin, Lianhua
中科院分区：
文献类型：
--
作者：
Ning, Yanxia;Bai, Qianming;Lu, Hong;Li, Xiaobo;Pandak, William M.;Zhao, Fengdi;Chen, Sifeng;Ren, Shunlin;Yin, Lianhua
高脂血症是动脉粥样硬化最重要的危险因素之一。这可以通过巨噬细胞介导的局部炎症反应放大。巨噬细胞能够吸收多余的胆固醇，众所周知，通过类固醇急性调节（StAR）蛋白将胆固醇传递到线粒体是肝脏中胆固醇降解的限速步骤。也有研究表明，肝细胞中StAR的过度表达会显著增加细胞核中调节性氧甾醇的数量，这在维持细胞内脂质稳态中起着重要作用。本研究的目的是确定StAR是否在巨噬细胞中起类似的作用。我们发现，在人THP-1单核细胞源性巨噬细胞中，过表达StAR可降低细胞内脂质水平，激活肝脏X受体α (LXRα)和增殖过氧体激活剂受体γ (PPARγ)，并增加ABCG1和CYP27A1的表达。此外，它可以减少炎症因子的分泌，防止细胞凋亡。这些结果表明，StAR将胆固醇传递到线粒体，在线粒体中产生调节氧化甾醇。调节性氧甾醇可以反过来激活核受体，从而增加胆固醇外排转运体的表达，减少炎症因子的分泌。这些作用可防止巨噬细胞凋亡。这些结果暗示了StAR在预防动脉粥样硬化中的潜在作用。
Hyperlipidemia is one of the most important risk factors for atherosclerosis. This can be amplified by a localized inflammatory response mediated by macrophages. Macrophages are capable of taking up excess cholesterol, and it is well known that delivery of cholesterol to the mitochondria by steroidogenic acute regulatory (StAR) protein is the rate-limiting step for cholesterol degradation in the liver. It has also been shown that overexpression of StAR in hepatocytes dramatically increases the amount of regulatory oxysterols in the nucleus, which play an important role in the maintenance of intracellular lipid homeostasis. The goal of the present studywas to determine whether StAR plays a similar role in macrophages. We have found that overexpression of StAR in human THP-1 monocyte-derived macrophages decreases intracellular lipid levels, activates liver X receptor alpha (LXRα) and proliferation peroxysome activator receptor gamma (PPARγ), and increases ABCG1 and CYP27A1 expression. Furthermore, it reduces the secretion of inflammatory factors, and prevents apoptosis. These results suggest that StAR delivers cholesterol to mitochondria where regulatory oxysterols are generated. Regulatory oxysterols can in turn activate nuclear receptors, which increase expression of cholesterol efflux transporters, and decrease secretion of inflammatory factors. These effects can prevent macrophage apoptosis. These results imply a potential role of StAR in the prevention of atherosclerosis.
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影响因子：
6.7
作者：
Ma, Y.;Ren, S.;Yin, L.
通讯作者：
Yin, L.
影响因子：
4.8
作者：
Pandak, WM;Ren, SL;Hylemon, P
通讯作者：
Hylemon, P
DOI：
10.1073/pnas.200367697
发表时间：
2000-10-24
影响因子：
11.1
作者：
Venkateswaran, A;Laffitte, BA;Tontonoz, P
通讯作者：
Tontonoz, P
影响因子：
82.9
作者：
Chinetti, G;Lestavel, S;Staels, B
通讯作者：
Staels, B
DOI：
10.1016/j.bbrc.2007.06.143
发表时间：
2007-09-07
影响因子：
3.1
作者：
Ren, Shunlin;Li, Xiaobo;Pandak, William M.
通讯作者：
Pandak, William M.