Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P51532 (
transcriptional activator
)
6,546
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, reduces
brain edema
in patients with acute ischemic stroke. We have addressed the effect of edaravone on the expression of vascular endothelial growth factor (VEGF), a potential mediator of
brain edema
, in astrocytes exposed to hypoxia. Normal human astrocytes in culture were treated with edaravone, and the levels of VEGF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). The expression of hypoxia-inducible factor-1alpha (HIF-1alpha), a
transcriptional activator
of VEGF, was examined by RT-PCR, real-time PCR and western blotting; and the binding of HIF-1alpha to the promoter region of VEGF gene by chromatin immunoprecipitation (ChIP) assay. Edaravone moderately suppressed the expression of VEGF mRNA and protein in astrocytes under hypoxia in time- and concentration-dependent manners. It also suppressed the accumulation of HIF-1alpha in the nuclei under hypoxia. ChIP assay confirmed that edaravone reduced HIF-1alpha binding to VEGF promoter. We conclude that edaravone inhibits VEGF expression in astrocytes exposed to hypoxia, at least partly, through the down-regulation of HIF-1alpha. These findings offer a partial explanation for the protective effect of edaravone on the development of
brain edema
in patients with acute ischemic stroke.
...
PMID:Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. 1788 87
