Abstract
Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The iron-chelator desferrioxamine (DFX) increased the expression of hypoxia-inducible factor (HIF)-1alpha in the hair cell line, HEI-OC1. The increased VEGF production by DFX was inhibited by iron. DFX also induced the activation of mitogen-activated protein kinase (MAPK) on HEI-OC1. The increased VEGF production by DFX was inhibited by a specific inhibitor of MAPK. In addition, DFX induced the VEGF production and HIF-1alpha stabilization in vivo. These results indicate that VEGF production is regulated via MAPK and HIF-1alpha under hypoxic condition in the inner ear.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Hypoxia / physiology
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Cell Line
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Cells, Cultured
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DNA-Binding Proteins / physiology*
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Ear, Inner / metabolism*
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Enzyme Activation / physiology
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Mice
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Mice, Transgenic
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Mitogen-Activated Protein Kinases / physiology*
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Nuclear Proteins / physiology*
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Stress, Physiological / metabolism*
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Stress, Physiological / physiopathology*
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Transcription Factors / physiology*
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Vascular Endothelial Growth Factor A / biosynthesis*
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Vascular Endothelial Growth Factor A / genetics
Substances
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DNA-Binding Proteins
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Hif1a protein, mouse
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Hypoxia-Inducible Factor 1
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Hypoxia-Inducible Factor 1, alpha Subunit
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Nuclear Proteins
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Transcription Factors
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Vascular Endothelial Growth Factor A
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Mitogen-Activated Protein Kinases