Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand.

摘要: Abstract Endothelin-1 (ET-1) is a peptide hormone with potent vasoconstrictor properties that synthesized and secreted predominantly by vascular endothelial cells. Its production regulated numerous stimuli including ischemia hypoxia, the enhanced levels occur during myocardial may contribute to progression of heart failure. We previously reported ET-1 expression was induced both hypoxia transition metals in cells (ECs). Here we define an element proximal promoter gene responsible for this induction. By using deletions site directed mutagenesis human promoter, combination electrophoretic gel mobility shifts transient assays ECs, identified active hypoxia-inducible factor 1 (HIF-1) binding starting at position −118 upstream transcription start on non-coding DNA strand. Mutation eliminated induction without affecting basal (aerobic) expression, mutated sequence did not display hypoxia-specific HIF-1.