May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Evidence for Activation of the HIF–1 Pathway by Quercetin in Human Lens Epithelial Cells
Author Affiliations & Notes
  • J. Sanderson
    School of Chemical Sciences and Pharmacy,
    University of East Anglia, Norwich, United Kingdom
  • J.D. Rhodes
    School of Biological Sciences,
    University of East Anglia, Norwich, United Kingdom
  • K.C. Cornish
    School of Biological Sciences,
    University of East Anglia, Norwich, United Kingdom
  • J.R. Reddan
    Biological Sciences, Oakland University, Rochester, MI
  • P.R. Kroon
    Institute of Food Research, Norwich, United Kingdom
  • R. Mithen
    Institute of Food Research, Norwich, United Kingdom
  • Footnotes
    Commercial Relationships  J. Sanderson, None; J.D. Rhodes, None; K.C. Cornish, None; J.R. Reddan, None; P.R. Kroon, None; R. Mithen, None.
  • Footnotes
    Support  BBSRC
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3845. doi:
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      J. Sanderson, J.D. Rhodes, K.C. Cornish, J.R. Reddan, P.R. Kroon, R. Mithen; Evidence for Activation of the HIF–1 Pathway by Quercetin in Human Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3845.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To investigate the effect of the dietary flavonoid quercetin on gene expression in a human lens epithelial cell line. Methods: The human lens epithelial cell line (FHL–124) was cultured in serum free EMEM for the duration of the experiments. Cell death and cell proliferation were assessed by cell area measurements and [3H]–thymidine incorporation. Transcription profiles from confluent cells exposed to 10µM quercetin or vehicle only for 24 hours were analysed using the IFR human oligonucleotide gene array (a 14 000 gene 2–colour cDNA microarray). Data were analysed using GenePix and GeneSpring software. Results: Exposure of human lens epithelial cells to 50 µM H2O2 for 24 hours resulted in decreases in cell proliferation and cell death. Pre–incubation of the cells with quercetin (10µM) for 24 hours, followed by exposure of cells to the oxidative stress in the absence of quercetin, protected against H2O2–induced cell death. This suggests that quercetin may cause changes in gene expression that protect against oxidative cell death. Global gene expression was analysed from duplicate experiments following incubation of cells with 10µM quercetin for 24 hours. Comparison of transcript profiles between control and quercetin–treated cells identified 22 genes for which increased expression was highly significant (p≤0.01) and 10 genes for which expression significantly decreased (p≤0.01). Interestingly, of the genes showing increased expression, more than half (12 genes) are reported to be induced by hypoxia via the HIF–1 pathway. These include AK 3 (normalised expression = 2.99), BNIP3 (normalised expression = 2.84) and PGK1 (normalised expression = 2.14). Conclusions: Quercetin causes the increased expression of HIF–1 target genes. This may play a role in protection against oxidative stress in lens epithelial cells.

Keywords: oxidation/oxidative or free radical damage • hypoxia • nutritional factors 
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