PMID- 19729006
OWN - NLM
STAT- MEDLINE
DCOM- 20100205
LR  - 20131121
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 89
IP  - 6
DP  - 2009 Dec
TI  - Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens 
      epithelial cells.
PG  - 995-1002
LID - 10.1016/j.exer.2009.08.011 [doi]
AB  - 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 microM) 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 microM) induced a time-dependent increase 
      in HIF-1alpha protein levels. Quercetin (30 microM) was also responsible for a 
      rapid and long-lasting translocation of HIF-1alpha 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-1alpha was reversed by addition of 
      excess iron (100 microM). These results demonstrate that quercetin activates the 
      HIF-1 signaling pathway in human lens epithelial cells.
FAU - Radreau, Pauline
AU  - Radreau P
AD  - School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK.
FAU - Rhodes, Jeremy D
AU  - Rhodes JD
FAU - Mithen, Richard F
AU  - Mithen RF
FAU - Kroon, Paul A
AU  - Kroon PA
FAU - Sanderson, Julie
AU  - Sanderson J
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090901
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Antioxidants)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (RNA, Messenger)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Blotting, Western/methods
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/genetics/*physiology
MH  - Lens Capsule, Crystalline/cytology/*drug effects/metabolism
MH  - Microarray Analysis/methods
MH  - Quercetin/*pharmacology
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Signal Transduction/drug effects
EDAT- 2009/09/05 06:00
MHDA- 2010/02/06 06:00
CRDT- 2009/09/05 06:00
PHST- 2009/07/02 00:00 [received]
PHST- 2009/08/14 00:00 [revised]
PHST- 2009/08/24 00:00 [accepted]
PHST- 2009/09/05 06:00 [entrez]
PHST- 2009/09/05 06:00 [pubmed]
PHST- 2010/02/06 06:00 [medline]
AID - S0014-4835(09)00253-X [pii]
AID - 10.1016/j.exer.2009.08.011 [doi]
PST - ppublish
SO  - Exp Eye Res. 2009 Dec;89(6):995-1002. doi: 10.1016/j.exer.2009.08.011. Epub 2009 
      Sep 1.