Ries, Stefan and Büchler, Christa and Langmann, Thomas and Fehringer, Petra and Aslanidis, Charalampos and Schmitz, Gerd (1998) Transcriptional regulation of lysosomal acid lipase in differentiating monocytes is mediated by transcription factors Sp1 and AP-2. JOURNAL OF LIPID RESEARCH, 39 (11). pp. 2125-2134. ISSN 0022-2275,
Full text not available from this repository. (Request a copy)Abstract
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 Spl 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.jlr Our data suggest that differentiation dependent increase of lysosomal acid lipase (LAL) expression in THP-I cells is mediated by a concerted action of Sp1 and AP-2.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHOLESTERYL ESTER HYDROLASE; GENE-EXPRESSION; WOLMAN-DISEASE; MESSENGER-RNA; RECEPTOR GENE; TFIID COMPLEX; CELLS; PROMOTER; ATHEROSCLEROSIS; ACTIVATION; cholesterol metabolism; acid lipase; lysosome; macrophage; differentiation; LAL-promoter; transcription factors; gene regulation; Wolman disease; cholesteryl ester storage disease |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Apr 2023 09:00 |
| Last Modified: | 18 Apr 2023 09:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49393 |
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