PMID- 9746763
OWN - NLM
STAT- MEDLINE
DCOM- 19981019
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 92
IP  - 7
DP  - 1998 Oct 1
TI  - Induction of endothelial PAS domain protein-1 by hypoxia: characterization and 
      comparison with hypoxia-inducible factor-1alpha.
PG  - 2260-8
AB  - Hypoxia results in adaptive changes in the transcription of a range of genes 
      including erythropoietin. An important mediator is hypoxia-inducible factor-1 
      (HIF-1), a DNA binding complex shown to contain at least two basic 
      helix-loop-helix PAS-domain (bHLH-PAS) proteins, HIF-1alpha and aryl hydrocarbon 
      nuclear receptor translocator (ARNT). In response to hypoxia, HIF-1alpha is 
      activated and accumulates rapidly in the cell. Endothelial PAS domain protein 1 
      (EPAS-1) is a recently identified bHLH-PAS protein with 48% identity to 
      HIF-1alpha, raising the question of its role in responses to hypoxia. We 
      developed specific antibodies and studied expression and regulation of EPAS-1 
      mRNA and protein across a range of human cell lines. EPAS-1 was widely expressed, 
      and strongly induced by hypoxia at the level of protein but not mRNA. Comparison 
      of the effect of a range of activating and inhibitory stimuli showed striking 
      similarities in the EPAS-1 and HIF-1alpha responses. Although major differences 
      were observed in the abundance of EPAS-1 and HIF-1alpha in different cell types, 
      differences in the inducible response were subtle with EPAS-1 protein being 
      slightly more evident in normoxic and mildly hypoxic cells. Functional studies in 
      a mutant cell line (Ka13) expressing neither HIF-1alpha nor EPAS-1 confirmed that 
      both proteins interact with hypoxically responsive targets, but suggest target 
      specificity with greater EPAS-1 transactivation (relative to HIF-1alpha 
      transactivation) of the VEGF promoter than the LDH-A promoter.
FAU - Wiesener, M S
AU  - Wiesener MS
AD  - Institute of Molecular Medicine and the Department of Cellular Science, John 
      Radcliffe Hospital, Oxford, UK.
FAU - Turley, H
AU  - Turley H
FAU - Allen, W E
AU  - Allen WE
FAU - Willam, C
AU  - Willam C
FAU - Eckardt, K U
AU  - Eckardt KU
FAU - Talks, K L
AU  - Talks KL
FAU - Wood, S M
AU  - Wood SM
FAU - Gatter, K C
AU  - Gatter KC
FAU - Harris, A L
AU  - Harris AL
FAU - Pugh, C W
AU  - Pugh CW
FAU - Ratcliffe, P J
AU  - Ratcliffe PJ
FAU - Maxwell, P H
AU  - Maxwell PH
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (ARNT protein, human)
RN  - 0 (Arnt protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Onium Compounds)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 3G0H8C9362 (Cobalt)
RN  - 6HJ411TU98 (diphenyleneiodonium)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EVS87XF13W (cobaltous chloride)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - CHO Cells
MH  - COS Cells
MH  - Cell Hypoxia/*physiology
MH  - Cell Line
MH  - Cobalt/pharmacology
MH  - Cricetinae
MH  - Cricetulus
MH  - DNA-Binding Proteins/*biosynthesis/genetics
MH  - Deferoxamine/pharmacology
MH  - Endothelial Growth Factors/genetics
MH  - *Gene Expression Regulation
MH  - HeLa Cells/drug effects/metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Iron Chelating Agents/pharmacology
MH  - L-Lactate Dehydrogenase/genetics
MH  - Lymphokines/genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nuclear Proteins/*biosynthesis/genetics
MH  - Onium Compounds/pharmacology
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/biosynthesis
MH  - *Receptors, Aryl Hydrocarbon
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Trans-Activators/*biosynthesis/genetics
MH  - Transcription Factors/metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1998/09/25 00:00
MHDA- 1998/09/25 00:01
CRDT- 1998/09/25 00:00
PHST- 1998/09/25 00:00 [pubmed]
PHST- 1998/09/25 00:01 [medline]
PHST- 1998/09/25 00:00 [entrez]
AID - S0006-4971(20)74520-9 [pii]
PST - ppublish
SO  - Blood. 1998 Oct 1;92(7):2260-8.