PMID- 17898080
OWN - NLM
STAT- MEDLINE
DCOM- 20080319
LR  - 20220330
IS  - 1059-1524 (Print)
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Linking)
VI  - 18
IP  - 12
DP  - 2007 Dec
TI  - Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving 
      phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery 
      smooth muscle cells.
PG  - 4691-7
AB  - The oxygen sensitive alpha-subunit of the hypoxia-inducible factor-1 (HIF-1) is a 
      major trigger of the cellular response to hypoxia. Although the posttranslational 
      regulation of HIF-1alpha by hypoxia is well known, its transcriptional regulation 
      by hypoxia is still under debate. We, therefore, investigated the regulation of 
      HIF-1alpha mRNA in response to hypoxia in pulmonary artery smooth muscle cells. 
      Hypoxia rapidly enhanced HIF-1alpha mRNA levels and HIF-1alpha promoter activity. 
      Furthermore, inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT but not 
      extracellular signal-regulated kinase 1/2 pathway blocked the hypoxia-dependent 
      induction of HIF-1alpha mRNA and HIF-1alpha promoter activity, suggesting 
      involvement of a PI3K/AKT-regulated transcription factor. Interestingly, hypoxia 
      also induced nuclear factor-kappaB (NFkappaB) nuclear translocation and activity. 
      In line, expression of the NFkappaB subunits p50 and p65 enhanced HIF-1alpha mRNA 
      levels, whereas blocking of NFkappaB by an inhibitor of nuclear factor-kappaB 
      attenuated HIF-1alpha mRNA induction by hypoxia. Reporter gene assays revealed 
      the presence of an NFkappaB site within the HIF-1alpha promoter, and mutation of 
      this site abolished induction by hypoxia. In line, gel shift analysis and 
      chromatin immunoprecipitation confirmed binding of p50 and p65 NFkappaB subunits 
      to the HIF-1alpha promoter under hypoxia. Together, these findings provide a 
      novel mechanism in which hypoxia induces HIF-1alpha mRNA expression via the 
      PI3K/AKT pathway and activation of NFkappaB.
FAU - Belaiba, Rachida S
AU  - Belaiba RS
AD  - Experimental Pediatric Cardiology, Department of Pediatric Cardiology and 
      Congenital Heart Disease, German Heart Center Munich at the Technical University 
      Munich, D-80636 Munich, Germany.
FAU - Bonello, Steve
AU  - Bonello S
FAU - Zahringer, Christian
AU  - Zahringer C
FAU - Schmidt, Stefanie
AU  - Schmidt S
FAU - Hess, John
AU  - Hess J
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 - 20070926
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Arteries/metabolism
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Humans
MH  - Hypoxia/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - RNA, Messenger/genetics
MH  - Signal Transduction
MH  - Transcription, Genetic/*genetics
MH  - Up-Regulation/*genetics
PMC - PMC2096613
EDAT- 2007/09/28 09:00
MHDA- 2008/03/20 09:00
PMCR- 2008/01/27
CRDT- 2007/09/28 09:00
PHST- 2007/09/28 09:00 [pubmed]
PHST- 2008/03/20 09:00 [medline]
PHST- 2007/09/28 09:00 [entrez]
PHST- 2008/01/27 00:00 [pmc-release]
AID - E07-04-0391 [pii]
AID - 3279168 [pii]
AID - 10.1091/mbc.e07-04-0391 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2007 Dec;18(12):4691-7. doi: 10.1091/mbc.e07-04-0391. Epub 2007 
      Sep 26.