PMID- 12054621
OWN - NLM
STAT- MEDLINE
DCOM- 20020705
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 293
IP  - 1
DP  - 2002 Apr 26
TI  - The dietary flavonoid quercetin modulates HIF-1 alpha activity in endothelial 
      cells.
PG  - 446-50
AB  - The mechanism of activation of the transcription factor hypoxia-inducible 
      factor-1 (HIF-1) has been studied extensively. Under normal cellular oxygen 
      conditions protein levels of the alpha subunit (HIF-1 alpha) are kept low due to 
      massive ubiquitination and subsequent proteosomal degradation. However, during 
      hypoxia ubiquitination is inhibited, causing stabilisation of the HIF-1 alpha 
      protein. HIF-1 alpha can then translocate to the nucleus and facilitate 
      transcription of numerous target genes, the majority of which are involved in 
      glycolysis and angiogenesis via heterodimerisation with the beta subunit (HIF-1 
      beta/ARNT). Until now hypoxia has been the only naturally occurring signal shown 
      to activate this transcription factor. We report here that the dietary flavonoid 
      quercetin also activates HIF-1 alpha in all steps of its activation pathway, in a 
      manner similar to hypoxia. We found that quercetin, an inhibitor of Ser/Thr 
      kinases, stabilises HIF-1 alpha and causes nuclear localisation of the protein in 
      a transcriptionally active state. Taken together these results strongly indicate 
      that the dietary flavonoid quercetin regulates HIF-1 function at normal oxygen 
      concentrations.
FAU - Wilson, William J
AU  - Wilson WJ
AD  - Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska 
      Institutet, S-171 77 Stockholm, Sweden.
FAU - Poellinger, Lorenz
AU  - Poellinger L
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 9IKM0I5T1E (Quercetin)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Luciferases/genetics/metabolism
MH  - Mice
MH  - Phosphorylation
MH  - Quercetin/*pharmacology
MH  - Recombinant Proteins/metabolism
MH  - Transcription Factors/drug effects/*metabolism
MH  - Transfection
EDAT- 2002/06/11 10:00
MHDA- 2002/07/06 10:01
CRDT- 2002/06/11 10:00
PHST- 2002/06/11 10:00 [pubmed]
PHST- 2002/07/06 10:01 [medline]
PHST- 2002/06/11 10:00 [entrez]
AID - S0006-291X(02)00244-9 [pii]
AID - 10.1016/S0006-291X(02)00244-9 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2002 Apr 26;293(1):446-50. doi: 
      10.1016/S0006-291X(02)00244-9.