Ries S, Büchler C, Langmann T, Fehringer P, Aslanidis C, Schmitz G
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, D-93042 Regensburg, Germany.
J Lipid Res. 1998 Nov;39(11):2125-34.
Human lysosomal acid lipase (LAL) is a hydrolase required for the cleavage of cholesteryl esters and triglycerides derived from plasma lipoproteins. It is shown here that during monocyte to macrophage differentiation, the expression of LAL-mRNA is induced. This induction is dependent on protein kinase C activity and protein synthesis. The cell type-specific increase in LAL expression is further investigated in the THP-1 cell line with respect to transcriptional regulation. The human monocytic leukemia cell line THP-1 differentiates into macrophage-like cells when treated with phorbol esters. In order to determine the cis-acting elements necessary for both basal and phorbol 12-myristate-13 acetate (PMA)-enhanced promoter activity, we performed deletion analysis and reporter gene assays. A PMA responsive element has been identified between -182 bp and -107 bp upstream of the major transcription start site. Gel mobility shift assays demonstrated that binding of Sp1 and AP-2 to the LAL promoter is increased by PMA in THP-1 cells. Co-transfections with expression plasmids for Sp1 and AP-2 further emphasized the important role of these transcription factors in both basal and PMA-enhanced LAL expression. Our data suggest that differentiation dependent increase of lysosomal acid lipase (LAL) expression in THP-1 cells is mediated by a concerted action of Sp1 and AP-2.
人溶酶体酸性脂肪酶（LAL）是一种水解酶，用于裂解源自血浆脂蛋白的胆固醇酯和甘油三酯。本文显示，在单核细胞向巨噬细胞分化过程中，LAL-mRNA的表达被诱导。这种诱导依赖于蛋白激酶C活性和蛋白质合成。关于转录调控，在THP-1细胞系中进一步研究了LAL表达的细胞类型特异性增加。人单核细胞白血病细胞系THP-1在用佛波酯处理时会分化为巨噬细胞样细胞。为了确定基础和佛波醇12-肉豆蔻酸酯-13-乙酸酯（PMA）增强的启动子活性所需的顺式作用元件，我们进行了缺失分析和报告基因测定。在主要转录起始位点上游-182 bp至-107 bp之间鉴定出一个PMA反应元件。凝胶迁移率变动分析表明，在THP-1细胞中，PMA可增加Sp1和AP-2与LAL启动子的结合。用Sp1和AP-2的表达质粒进行共转染进一步强调了这些转录因子在基础和PMA增强的LAL表达中的重要作用。我们的数据表明，THP-1细胞中溶酶体酸性脂肪酶（LAL）表达的分化依赖性增加是由Sp1和AP-2的协同作用介导的。
