PMID- 10607702
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20220310
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 95
IP  - 1
DP  - 2000 Jan 1
TI  - Hypoxia response element of the human vascular endothelial growth factor gene 
      mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible 
      factor-1 activity by nitric oxide.
PG  - 189-97
AB  - Nitric oxide (NO) regulates production of vascular endothelial growth factor 
      (VEGF) by normal and transformed cells. We demonstrate that NO donors may 
      up-regulate the activity of the human VEGF promoter in normoxic human 
      glioblastoma and hepatoma cells independent of a cyclic guanosine 
      monophosphate-mediated pathway. Deletion and mutation analysis of the VEGF 
      promoter indicates that the NO-responsive cis-elements are the hypoxia-inducible 
      factor-1 (HIF-1) binding site and an adjacent ancillary sequence that is located 
      immediately downstream within the hypoxia-response element (HRE). This work 
      demonstrates that the HRE of this promoter is the primary target of NO. In 
      addition, VEGF gene regulation by NO, as well as by hypoxia, is potentiated by 
      the AP-1 element of the gene. Our study also reveals that NO and hypoxia induce 
      an increase in HIF-1 binding activity and HIF-1alpha protein levels, both in the 
      nucleus and the whole cell. These results suggest that there are common features 
      of the NO and hypoxic pathways of VEGF induction, while in part, NO mediates gene 
      transcription by a mechanism distinct from hypoxia. This is demonstrated by a 
      difference in sensitivity to guanylate cyclase inhibitors and a different pattern 
      of HIF-1 binding. These results show that there is a primary role for NO in the 
      control of VEGF synthesis and in cell adaptations to hypoxia. (Blood. 
      2000;95:189-197)
FAU - Kimura, H
AU  - Kimura H
AD  - Investigative Treatment Division, National Cancer Center Research Institute East, 
      Kashiwa, Chiba, Japan.
FAU - Weisz, A
AU  - Weisz A
FAU - Kurashima, Y
AU  - Kurashima Y
FAU - Hashimoto, K
AU  - Hashimoto K
FAU - Ogura, T
AU  - Ogura T
FAU - D'Acquisto, F
AU  - D'Acquisto F
FAU - Addeo, R
AU  - Addeo R
FAU - Makuuchi, M
AU  - Makuuchi M
FAU - Esumi, H
AU  - Esumi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 79032-48-7 (S-Nitroso-N-Acetylpenicillamine)
RN  - EC 1.13.12.- (Luciferases)
RN  - GNN1DV99GX (Penicillamine)
SB  - IM
MH  - Base Sequence
MH  - Cell Hypoxia/*physiology
MH  - Cell Line
MH  - DNA-Binding Proteins/*metabolism
MH  - Endothelial Growth Factors/*genetics
MH  - *Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kinetics
MH  - Luciferases/biosynthesis/genetics
MH  - Lymphokines/*genetics
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Donors/*pharmacology
MH  - Nuclear Proteins/*metabolism
MH  - Penicillamine/*analogs & derivatives/pharmacology
MH  - *Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - *Regulatory Sequences, Nucleic Acid
MH  - S-Nitroso-N-Acetylpenicillamine
MH  - Sequence Deletion
MH  - Transcription Factors/metabolism
MH  - *Transcription, Genetic/drug effects
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - S0006-4971(20)36605-2 [pii]
PST - ppublish
SO  - Blood. 2000 Jan 1;95(1):189-97.