| Autor: |
Layton Harris Smith, Matthew S. Petrie, Jason D. Morrow, John A. Oates, Douglas E. Vaughan |
| Jazyk: |
angličtina |
| Rok vydání: |
2005 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 46, Iss 5, Pp 862-871 (2005) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M500021-JLR200 |
| Popis: |
We previously demonstrated that cholesterol deprivation increases endothelial cyclooxygenase-2 (COX-2)-dependent prostacyclin [prostaglandin I2 (PGI2)] production in vitro. Cholesterol directly regulates gene transcription through the sterol response element binding protein (SREBP). In this work, we demonstrate that SREBP directly regulates COX-2 expression. Cholesterol reduces human COX-2 promoter-luciferase reporter construct activity in transiently transfected endothelial cells. Conversely, cotransfection with a constitutively active mutant SREBP increases COX-2 promoter activity. SREBP-1a and -2 specifically bind a putative sterol response element (SRE) sequence in the COX-2 promoter. This sequence competes for SREBP binding to a low density lipoprotein receptor consensus sequence in an electromobility-shift assay. These data indicate that endothelial COX-2 is regulated by cholesterol via the SREBP pathway.The present study identifies COX-2 as the first vascular gene without a clear role in lipid metabolism transactivated by SREBP, and suggests that enhanced production of PGI2 through this pathway may be an additional benefit of cholesterol-lowering therapies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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