PMID- 12900407
OWN - NLM
STAT- MEDLINE
DCOM- 20031202
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 41
DP  - 2003 Oct 10
TI  - AMP-activated protein kinase activity is critical for hypoxia-inducible factor-1 
      transcriptional activity and its target gene expression under hypoxic conditions 
      in DU145 cells.
PG  - 39653-61
AB  - AMP-activated protein kinase (AMPK) functions as an energy sensor to provide 
      metabolic adaptations under the ATP-deprived conditions such as hypoxia. In the 
      present study, we considered a role of AMPK in the adaptive response to hypoxia 
      by examining whether AMPK is involved in the regulation of hypoxia-inducible 
      factor-1 (HIF-1), a heterodimeric transcription factor that is critical for 
      hypoxic induction of physiologically important genes. We demonstrate that hypoxia 
      or CoCl2 rapidly activated AMPK in DU145 human prostate cancer cells, and its 
      activation preceded the induction of HIF-1 alpha expression. Under these 
      conditions, blockade of AMPK activity by a pharmacological or molecular approach 
      significantly attenuated hypoxia-induced responses such as HIF-1 target gene 
      expression, secretion of vascular endothelial growth factor, glucose uptake, and 
      HIF-1-dependent reporter gene expression, indicating that AMPK is critical for 
      the HIF-1 transcriptional activity and its target gene expression. Its functional 
      requirement for HIF-1 activity was also demonstrated in several different cancer 
      cell lines, but AMPK activation alone was not sufficient to stimulate the HIF-1 
      transcriptional activity. We further present data showing that AMPK transmits a 
      positive signal for HIF-1 activity via a signaling pathway that is independent of 
      phosphatidylinositol 3-kinase/AKT and several mitogen-activated protein kinases. 
      Taken together, our results suggest that AMPK is a novel and critical component 
      of HIF-1 regulation, implying its new roles in oxygen-regulated cellular 
      phenomena.
FAU - Lee, Minyoung
AU  - Lee M
AD  - Department of Molecular Biology, Medical Research Center for Bioreaction to 
      Reactive Oxygen Species, Kyung Hee University College of Medicine, Seoul, Korea.
FAU - Hwang, Jin-Taek
AU  - Hwang JT
FAU - Lee, Hye-Jeong
AU  - Lee HJ
FAU - Jung, Seung-Nam
AU  - Jung SN
FAU - Kang, Insug
AU  - Kang I
FAU - Chi, Sung-Gil
AU  - Chi SG
FAU - Kim, Sung-Soo
AU  - Kim SS
FAU - Ha, Joohun
AU  - Ha J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20030804
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 3G0H8C9362 (Cobalt)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EVS87XF13W (cobaltous chloride)
SB  - IM
RIN - J Biol Chem. 2018 Nov 16;293(46):18013. PMID: 30446603
MH  - AMP-Activated Protein Kinases
MH  - Base Sequence
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Cobalt/pharmacology
MH  - DNA, Neoplasm/genetics
MH  - DNA-Binding Proteins/*genetics/*metabolism
MH  - Enzyme Activation
MH  - Gene Expression/drug effects
MH  - Glucose Transporter Type 1
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Male
MH  - Monosaccharide Transport Proteins/genetics
MH  - Multienzyme Complexes/*metabolism
MH  - Nuclear Proteins/*genetics/*metabolism
MH  - Prostatic Neoplasms/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Neoplasm/genetics/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/*genetics/*metabolism
MH  - Transcription, Genetic
MH  - Vascular Endothelial Growth Factor A/genetics
EDAT- 2003/08/06 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/08/06 05:00
PHST- 2003/08/06 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/08/06 05:00 [entrez]
AID - S0021-9258(20)83014-2 [pii]
AID - 10.1074/jbc.M306104200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Oct 10;278(41):39653-61. doi: 10.1074/jbc.M306104200. Epub 2003 
      Aug 4.