Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells

Radreau, Pauline, Rhodes, Jeremy D., Mithen, Richard C., Kroon, Paul A. and Sanderson, Julie (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Experimental Eye Research, 89 (6). pp. 995-1002. ISSN 1096-0007

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Abstract

Quercetin is a dietary bioflavonoid which has been shown to inhibit lens opacification in a number of models of cataract. The objectives of this study were to determine gene expression changes in human lens epithelial cells in response to quercetin and to investigate in detail the mechanisms underlying the responses. FHL-124 cells were treated with quercetin (10 µM) and changes in gene expression were measured by microarray. It was found that 65% of the genes with increased expression were regulated by the hypoxia-inducible factor-1 (HIF-1) pathway. Quercetin (10 and 30 µM) induced a time-dependent increase in HIF-1a protein levels. Quercetin (30 µM) was also responsible for a rapid and long-lasting translocation of HIF-1a from the cytoplasm to the nucleus. Activation of HIF-1 signaling by quercetin was confirmed by qRT–PCR which showed upregulation of the HIF-1 regulated genes EPO, VEGF, PGK1 and BNIP3. Analysis of medium taken from FHL-124 cells showed a sustained dose-dependent increase in VEGF secretion following quercetin treatment. The quercetin-induced increase and nuclear translocation of HIF-1a was reversed by addition of excess iron (100 µM). These results demonstrate that quercetin activates the HIF-1 signaling pathway in human lens epithelial cells.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: Rachel Smith
Date Deposited: 07 Apr 2011 11:38
Last Modified: 21 Jul 2020 23:35
URI: https://ueaeprints.uea.ac.uk/id/eprint/28411
DOI: 10.1016/j.exer.2009.08.011

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