REGULATED EXPRESSION OF THE HUMAN ACETYLATED LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE AND ISOLATION OF PROMOTER SEQUENCES
REGULATED EXPRESSION OF THE HUMAN ACETYLATED LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE AND ISOLATION OF PROMOTER SEQUENCES
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DOI：
10.1073/pnas.89.17.8102
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发表时间：
1992-09-01
影响因子：
11.1
通讯作者：
GLASS, CK
中科院分区：
文献类型：
--
作者：
MOULTON, KS;WU, H;GLASS, CK
乙酰化低密度脂蛋白（AcLDL）受体在组织巨噬细胞从单核细胞前体分化后表达，并且已被提出在动脉粥样硬化病变中泡沫细胞的产生中发挥作用。在本研究中，THP-1人单核细胞白血病细胞被用来调查机制负责表达AcLDL受体基因后，佛波酯12-肉豆蔻酸酯13-乙酸酯（TPA）的治疗。TPA依赖的积累AcLDL受体mRNA的检测，直到12小时的滞后期后，并被封锁与放线菌酮同时治疗。此外，TPA依赖的诱导AcLDL受体的活性和mRNA水平的抑制维甲酸和地塞米松治疗。 人和牛AcLDL受体基因的启动子区的分离和序列分析表明高序列相似性。AP-1蛋白或其他已知转录因子的结合位点在两个物种之间不保守，这表明AcLDL受体表达需要新的因子。
The acetylated low density lipoprotein (AcLDL) receptor is expressed on tissue macrophages after their differentiation from monocyte precursors and has been proposed to play a role in the generation of foam cells in atherosclerotic lesions. In the present studies, THP-1 human monocytic leukemia cells were used to investigate mechanisms responsible for expression of the AcLDL receptor gene after treatment with phorbol 12-myristate 13-acetate (TPA). TPA-dependent accumulation of AcLDL receptor mRNA was not detected until after a lag phase of 12 hr and was blocked by concurrent treatment with cycloheximide. In addition, the TPA-dependent induction of AcLDL receptor activity and mRNA levels was inhibited by retinoic acid and dexamethasone treatment. Isolation and sequence analysis of the promoter regions for the human and bovine AcLDL receptor genes indicated high sequence similarity. Binding sites for AP-1 proteins or other known transcription factors were not conserved between the two species, suggesting that novel factors are required for AcLDL receptor expression.