Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10758519 | Biochemical and Biophysical Research Communications | 2013 | 6 Pages |
Abstract
The very low density lipoprotein receptor (VLDLr) is highly upregulated during hypoxia in mouse cardiomyocytes and in human and mouse ischemic hearts causing a detrimental lipid accumulation. To know how the gene is regulated is important for future studies. In this study, we have thoroughly mapped the 5â²-flanking region of the mouse VLDLr promoter and show that the hypoxia-mediated increase in VLDLr expression is dependent on Hif-1α binding to a hypoxia responsive element (HRE) located at â162 to â158 bp 5â²of translation start. We show that classical HRE sites and the previously described PPARγ and Sp1 binding are not involved in the hypoxia-induced regulation of the VLDLr promoter. Using a chromatin immunoprecipitation (ChIP) assay, we show that Hif-1α specifically binds and activates the mouse VLDLr promoter at the previously described non-classical HRE in HL-1 cells. We also show that the same HRE is present and active in response to hypoxia in human cardiomyocytes, however at a different location (â812 bp from translation start). These results conclude that in the hypoxic hearts of mice and men, the VLDLr gene is regulated by a direct binding of Hif-1α to the VLDLr promoter.
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Authors
Jeanna Perman Sundelin, Ulf Lidberg, Ali Moussavi Nik, Peter Carlsson, Jan Borén,