PMID- 12485909
OWN - NLM
STAT- MEDLINE
DCOM- 20030213
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 973
DP  - 2002 Nov
TI  - ERK and calcium in activation of HIF-1.
PG  - 448-53
AB  - HIF-1 (hypoxia-inducible factor-1) is the main transcription factor responsible 
      for increased gene expression in hypoxia. The oxygen-dependent regulation of 
      HIF-1 activity occurs at multiple levels in vivo. The mechanisms regulating 
      HIF-1alpha protein expression have been most extensively analyzed, but the ones 
      modulating HIF-1 transcriptional activity remain unclear. Changes in the 
      phosphorylation and/or redox status of HIF-1alpha certainly play a role. Here, we 
      show that ionomycin could activate HIF-1 transcriptional activity in a way that 
      is additive to the effect of hypoxia without affecting HIF-1alpha protein level 
      and HIF-1 DNA binding capacity. In addition, a calmodulin dominant-negative 
      mutant as well as BAPTA, an intracellular calcium chelator, inhibited the 
      hypoxia-induced HIF-1 activation. These results indicate that elevated calcium in 
      hypoxia could participate in HIF-1 activation. PD98059, an inhibitor of the ERK 
      pathway, but not KN-93, an inhibitor of calmodulin kinases II and IV, also 
      blocked HIF-1 activation by hypoxia and by ionomycin. Altogether, these results 
      suggest that calcium and calmodulin would act upstream of ERK in the hypoxia 
      signal transduction pathway leading to enhanced HIF-1 transcriptional activity.
FAU - Mottet, Denis
AU  - Mottet D
AD  - Laboratory of Biochemistry and Cellular Biology, University of Namur, 5000 Namur, 
      Belgium.
FAU - Michel, Gaetan
AU  - Michel G
FAU - Renard, Patricia
AU  - Renard P
FAU - Ninane, Noelle
AU  - Ninane N
FAU - Raes, Martine
AU  - Raes M
FAU - Michiels, Carine
AU  - Michiels C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 56092-81-0 (Ionomycin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*physiology
MH  - Calcium Signaling/*physiology
MH  - Carcinoma, Hepatocellular
MH  - Cell Hypoxia
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/drug effects/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Ionomycin/*pharmacology
MH  - Liver Neoplasms
MH  - MAP Kinase Signaling System/*physiology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Nuclear Proteins/drug effects/genetics/*metabolism
MH  - Plasmids
MH  - Transcription Factors/*metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2002/12/18 04:00
MHDA- 2003/02/14 04:00
CRDT- 2002/12/18 04:00
PHST- 2002/12/18 04:00 [pubmed]
PHST- 2003/02/14 04:00 [medline]
PHST- 2002/12/18 04:00 [entrez]
AID - 10.1111/j.1749-6632.2002.tb04681.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2002 Nov;973:448-53. doi: 10.1111/j.1749-6632.2002.tb04681.x.