DNA sequences responsible for reduced promoter activity of human phospholipid transfer protein by fibrate.
DNA sequences responsible for reduced promoter activity of human phospholipid transfer protein by fibrate.
复制标题
贝特导致人磷脂转移蛋白启动子活性降低的 DNA 序列。
DOI：
10.1006/bbrc.1999.1597
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Albers,JJ
中科院分区：
文献类型：
--
作者：
Tu,AY;Albers,JJ
磷脂转运蛋白（PLTP）在血脂和脂蛋白代谢中起重要作用。我们以前已经克隆和鉴定了人PLTP基因的启动子区。本研究的目的是确定人类PLTP基因的启动子活性是否受到降血脂药物贝特类药物的影响，并确定导致这种影响的DNA序列。结果表明，PLTP基因的启动子活性被非诺贝特显著降低，并且主要响应贝特降低效应的区域位于5′-侧翼区的-377和-230之间。DNA序列分析表明，从-342到-323和从-322到-299的DNA序列的每个区域都有两个重复序列，它们与过氧化物酶体增殖物激活受体（PPAR）的识别基序，即PPAR-responsive element（PPRE）反向同源。这些PPRE样序列的突变，特别是在-322到-299的突变，消除了贝特类对PLTP启动子活性的大部分降低作用。这些结果强烈表明，PPRE样元件是负责降低人PLTP基因的启动子活性贝特类。
Phospholipid transfer protein (PLTP) plays an important role in plasma lipid and lipoprotein metabolism. We have previously cloned and characterized the promoter region of the human PLTP gene. The present study was conducted to determine if the promoter activity of the human PLTP gene is affected by fibrate, a hypolipidemic drug, and to identify DNA sequences that are responsible for the effect. The results indicated that the promoter activity of the PLTP gene was significantly reduced by fenofibrate, and the area that was mainly responsive to the reducing effect by fibrate was located between −377 and −230 of the 5′-flanking region. The DNA sequence analysis suggested that each area of the DNA sequences from −342 to −323 and from −322 to −299 has two repeated sequences, which are inverted and homologous to the recognition motif of peroxisome proliferator-activated receptor (PPAR), namely the PPAR-responsive element (PPRE). Mutagenesis of these PPRE-like sequences, especially that at −322 to −299, abolished most of the reducing effects of fibrate on the PLTP promoter activity. These findings strongly suggest that the PPRE-like elements are responsible for the reduced promoter activity of the human PLTP gene by fibrate.