PMID- 17272744
OWN - NLM
STAT- MEDLINE
DCOM- 20070425
LR  - 20220408
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 27
IP  - 4
DP  - 2007 Apr
TI  - Reactive oxygen species activate the HIF-1alpha promoter via a functional 
      NFkappaB site.
PG  - 755-61
AB  - OBJECTIVE: Reactive oxygen species have been implicated as signaling molecules 
      modulating the activity of redox-sensitive transcription factors such as nuclear 
      factor kappa B (NF-kappaB). Recently, the transcription factor hypoxia-inducible 
      factor-1 (HIF-1), known to mediate gene expression by hypoxia, has been found to 
      be also activated by nonhypoxic factors in a redox-sensitive manner. We therefore 
      aimed to elucidate the link between these 2 important redox-sensitive 
      transcription factors. METHODS AND RESULTS: In pulmonary artery smooth muscle 
      cells, reactive oxygen species generated either by exogenous H2O2 or by a 
      NOX4-containing NADPH oxidase stimulated by thrombin activated or induced 
      NF-kappaB and HIF-1alpha. The reactive oxygen species-mediated HIF-1alpha 
      induction occurred on the transcriptional level and was dependent on NF-kappaB. 
      Transfection experiments with wild-type or mutant HIF-1alpha promoter constructs 
      revealed the presence of a yet unidentified NF-kappaB binding element. Gel shift 
      analyses and chromatin immunoprecipitation verified binding of NF-kappaB to this 
      site. Furthermore, reactive oxygen species enhanced expression of plasminogen 
      activator inhibitor-1, which was prevented by dominant-negative IkappaB or 
      mutation of the HIF-1 binding site within the plasminogen activator inhibitor-1 
      promoter. CONCLUSION: These findings show for the first time to our knowledge 
      that reactive oxygen species directly link HIF-1alpha and NF-kappaB, implicating 
      an important pathophysiological role of this novel pathway in disorders 
      associated with elevated levels of reactive oxygen species.
FAU - Bonello, Steve
AU  - Bonello S
AD  - Experimental Pediatric Cardiology, Department of Pediatric Cardiology and 
      Congenital Heart Disease, German Heart Center Munich at the TU Munich, 
      Lazarettstr. 36, D-80636 Munich, Germany.
FAU - Zahringer, Christian
AU  - Zahringer C
FAU - BelAiba, Rachida S
AU  - BelAiba RS
FAU - Djordjevic, Talija
AU  - Djordjevic T
FAU - Hess, John
AU  - Hess J
FAU - Michiels, Carine
AU  - Michiels C
FAU - Kietzmann, Thomas
AU  - Kietzmann T
FAU - Gorlach, Agnes
AU  - Gorlach A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070201
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Gene Expression Regulation
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - NF-kappa B/*metabolism/physiology
MH  - Plasminogen Activator Inhibitor 1/genetics
MH  - Promoter Regions, Genetic/*physiology
MH  - Pulmonary Artery/cytology
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Thrombin/pharmacology
MH  - Transcription, Genetic/physiology
EDAT- 2007/02/03 09:00
MHDA- 2007/04/26 09:00
CRDT- 2007/02/03 09:00
PHST- 2007/02/03 09:00 [pubmed]
PHST- 2007/04/26 09:00 [medline]
PHST- 2007/02/03 09:00 [entrez]
AID - 01.ATV.0000258979.92828.bc [pii]
AID - 10.1161/01.ATV.0000258979.92828.bc [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):755-61. doi: 
      10.1161/01.ATV.0000258979.92828.bc. Epub 2007 Feb 1.