Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia.

Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Research Abstract Details 

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Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Abstract Text:

Akira Ishikawa,Hidemi Yoshida,Norifumi Metoki,Tsutomu Toki,Tadaatsu Imaizumi,Tomoh Matsumiya,Koji Yamashita,Kageaki Taima,Kei Satoh,Akira Ishikawa,Hidemi Yoshida,Norifumi Metoki,Tsutomu Toki,Tadaatsu Imaizumi,Tomoh Matsumiya,Koji Yamashita,Kageaki Taima,Kei Satoh,

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.

Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Publishing Authors By Initials

A Ishikawa,H Yoshida,N Metoki,T Toki,T Imaizumi,T Matsumiya,K Yamashita,K Taima,K Satoh,A Ishikawa,H Yoshida,N Metoki,T Toki,T Imaizumi,T Matsumiya,K Yamashita,K Taima,K Satoh,

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Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuroscience research

VOLUME: 59

Page Numbers: 406-12

Journal Abbreviation: Neurosci. Res.

ISSN: 0168-0102

DAY: 17

MONTH: 08

YEAR: 2007

Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia.

AFFILIATION: Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan.

Country: Ireland

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MEDLINETA: Neurosci Res

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