Abstract |
Nitric oxide (NO) has been reported to modulate the vascular endothelial growth factor ( VEGF) gene by accumulating hypoxia-inducible factor-1alpha (HIF-1alpha) protein, but there is a contradiction among effects of various NO donors. The effects of NO donors including S-nitroso-N-acetyl- penicillamine (SNAP), S-nitroso- glutathione (GSNO), 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC18), 3-[(+/-)-(E)-ethyl-2(')-[(E)-hydroxyimino]-5-nitro-3-hexenecarbamoyl]- pyridine (NOR4), 3-morpholinosydnonimine (SIN-1), and nitroprusside (SNP) on the VEGF reporter gene were examined. SNAP, GSNO, NOC18, and NOR4 enhanced the VEGF reporter activity under normoxia and modulated the hypoxic induction. In contrast, SNP had only an inhibitory effect. An NO scavenger attenuated the reporter activation by NO donors except NOR4, but did not ameliorate the inhibitory effect of SNP. A reducing compound dithiothreitol suppressed NO-induced activation of the VEGF reporter gene. SNAP, GSNO, and NOC18 induced the accumulation of HIF-1alpha protein, while others did not. These results suggest that SNAP, GSNO, and NOC compounds are suitable for pharmacological studies in HIF-1-mediated VEGF gene activation by NO.
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Authors | Hideo Kimura, Tsutomu Ogura, Yukiko Kurashima, Alessandro Weisz, Hiroyasu Esumi |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 296
Issue 4
Pg. 976-82
(Aug 30 2002)
ISSN: 0006-291X [Print] United States |
PMID | 12200144
(Publication Type: Journal Article)
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Chemical References |
- 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene
- Endothelial Growth Factors
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- Lymphokines
- NOR 4
- Nitric Oxide Donors
- Nitrites
- Pyridines
- RNA, Messenger
- Reducing Agents
- S-nitro-N-acetylpenicillamine
- Transcription Factors
- Triazenes
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Nitroprusside
- Nitric Oxide
- S-Nitrosoglutathione
- linsidomine
- RNA
- Molsidomine
- Luciferases
- Penicillamine
- Dithiothreitol
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Topics |
- Blotting, Northern
- Blotting, Western
- Cell Nucleus
(metabolism)
- Dithiothreitol
(pharmacology)
- Dose-Response Relationship, Drug
- Endothelial Growth Factors
(genetics, metabolism)
- Genes, Reporter
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
- Luciferases
(metabolism)
- Lymphokines
(genetics, metabolism)
- Molsidomine
(analogs & derivatives, pharmacology)
- Nitric Oxide
(metabolism)
- Nitric Oxide Donors
(pharmacology)
- Nitrites
(metabolism)
- Nitroprusside
(pharmacology)
- Oxidation-Reduction
- Penicillamine
(analogs & derivatives, pharmacology)
- Plasmids
(metabolism)
- Promoter Regions, Genetic
- Pyridines
(pharmacology)
- RNA
(metabolism)
- RNA, Messenger
(metabolism)
- Reducing Agents
(pharmacology)
- S-Nitrosoglutathione
(pharmacology)
- Transcription Factors
(metabolism)
- Triazenes
(pharmacology)
- Tumor Cells, Cultured
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
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