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

Journal of Cellular Biochemistry
Nélida C OlavePaul J Higgins

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 in...Continue Reading

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Citations

May 9, 2013·The Journal of Biological Chemistry·Miyuki MatsudaSatoshi Umemura
Jan 24, 2017·Drug Discovery Today·Abel Soto-Gamez, Marco Demaria
Sep 14, 2017·BMC Genomics·Camila M Lopes-RamosKimberly Glass
Apr 16, 2016·F1000Research·Surinder Kumar, David B Lombard
Sep 27, 2020·Cardiovascular Drugs and Therapy·Emily DookunGavin D Richardson
Oct 27, 2020·Stem Cells International·Provvidenza M AbruzzoCarlo Ventura
Nov 24, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Yuxuan WangMinghua Wu
Apr 17, 2021·Frontiers in Cardiovascular Medicine·Olina DagherMichel Carrier
May 23, 2021·Experimental Gerontology·Mojtaba ParviziIan R Lanza
Mar 12, 2021·Endocrinology·Allyson K PalmerJames L Kirkland
Jul 9, 2021·Mechanisms of Ageing and Development·W Andrew OwensGavin D Richardson

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