Upstream stimulatory factor-2 mediates quercetin-induced suppression of PAI-1 gene expression in human endothelial cells

Nélida C. Olave, Maximiliano H. Grenett, Martin Cadeiras, Hernan E. Grenett, Paul J. Higgins

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The polyphenol quercetin (Quer) represses expression of the cardiovascular disease risk factor plasminogen activator inhibitor-1 (PAI-1) in cultured endothelial cells (ECs). Transfection of PAI-1 promoter-luciferase reporter deletion constructs identified a 251-bp fragment (nucleotides -800 to -549) responsive to Quer. Two E-box motifs (CACGTG), at map positions -691 (E-box1) and -575 (E-box2), are platforms for occupancy by several members of the c-MYC family of basic helix-loop-helix leucine zipper (bHLH-LZ) proteins. Promoter truncation and electrophoretic mobility shift/supershift analyses identified upstream stimulatory factor (USF)-1 and USF-2 as E-box1/E-box2 binding factors. ECs co-transfected with a 251 bp PAI-1 promoter fragment containing the two E-box motifs (p251/luc) and a USF-2 expression vector (pUSF-2/pcDNA) exhibited reduced luciferase activity versus p251/luc alone. Overexpression of USF-2 decreased, while transfection of a dominant-negative USF construct increased, EC growth consistent with the known anti-proliferative properties of USF proteins. Quer-induced decreases in PAI-1 expression and reduced cell proliferation may contribute, at least in part, to the cardioprotective benefit associated with daily intake of polyphenols.

Original languageEnglish (US)
Pages (from-to)720-726
Number of pages7
JournalJournal of Cellular Biochemistry
Volume111
Issue number3
DOIs
StatePublished - Oct 15 2010
Externally publishedYes

Keywords

  • Endothelial Cells
  • PAI-1
  • Proliferation
  • Transcription Factor
  • Transfection
  • USF

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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