Activation of the rat scavenger receptor class B type I gene by PPARα

Activation of the rat scavenger receptor class B type I gene by PPARα
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DOI:
10.1016/j.mce.2006.02.011
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发表时间:
2006-06-07
影响因子:
4.1
通讯作者:
McLean, Mark P.
McLean, Mark P.
中科院分区:
医学2区
文献类型:
--
作者:
Lopez, Dayarni;McLean, Mark P.

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过氧化物酶体增殖物激活受体α (PPAR α)被已知可预防动脉粥样硬化的贝特类药物激活。本研究探讨了PPARa对SR-BI表达的影响。在本研究中,将大鼠SR-BI启动子-荧光素酶报告基因构建物共转染到不同细胞系中,并使用编码PPAR α视黄酸X受体α (RXR α)的表达载体。PPAR α /RXR增加SR-BI启动子的活性,clofibrate增强了这一作用。大鼠SR-BI启动子的序列分析显示,在bp - 1622上存在一个假定的过氧化物酶体增殖反应元件(PPRE)。电泳迁移率转移实验表明,PPAR α和RXRa能够结合SR-BI的PPRE基序。此外,突变分析研究证实,该PPRE基序负责PPAR α /RXR α依赖性激活大鼠SR-BI启动子。2006爱思唯尔爱尔兰有限公司版权所有。
Peroxisomal proliferator activated receptor alpha (PPAR alpha) is activated by fibrate drugs which are known to protect against atherosclerosis. The present study examines the effects of PPARa on SR-BI expression. For this study, a rat SR-BI promoter-luciferase reporter gene construct was co-transfected into different cell lines with expression vectors that encode for PPAR alpha retinoic X receptor alpha (RXR alpha). PPAR alpha/RXR increased the activity of the SR-BI promoter, an effect that was enhanced by clofibrate. Sequence analysis of the rat SR-BI promoter revealed the presence of a putative peroxisomal proliferator response element (PPRE) at bp - 1622. Electrophoretic mobility shift assays demonstrated that PPAR alpha and RXRa are able to bind to the SR-BI PPRE motif. In addition, mutational analysis studies confirmed that this PPRE motif is responsible for the PPAR alpha/RXR alpha-dependent activation of the rat SR-BI promoter in the cell lines examined. (c) 2006 Elsevier Ireland Ltd. All rights reserved.