Vascular endothelial growth factor is regulated by hypoxic stress via MAPK and HIF-1 alpha in the inner ear.
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.
Jeong
Hyun-Ja
HJ
College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
Kim
Joon-Bae
JB
Hong
Seung-Heon
SH
An
Nyeon-Hyoung
NH
Kim
Min-Sun
MS
Park
Byung-Rim
BR
Park
Rae-Kil
RK
Kim
Hyung-Min
HM
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D007758:Ear, Inner / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology*; D014157:Transcription Factors / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D020928:Mitogen-Activated Protein Kinases