The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions.
Von Hippel-Lindau protein (pVHL) normally functions to cause ubiquitin-mediated degradation of hypoxia-inducible factor-1alpha (HIF-1alpha) under normoxic but not under hypoxic conditions, and induces neuronal differentiation of neural progenitor cells. However, the role of pVHL in the differentiation of neural progenitor cells under either condition has not been fully elucidated. Herein, we show that under the anoxic condition the expression of pVHL and neuronal markers in neural progenitor cells was inhibited, while HIF-1alpha was induced. In addition, neural progenitor cells expressing pVHL following gene transfer showed distinct neuronal differentiation and no induction of HIF-1alpha under the normoxic condition but not under the anoxic condition. In conclusion, neuronal differentiation induced by pVHL is associated with degradation of HIF-1alpha and occurs normally under the normoxic condition but not under the anoxic condition. Differentiation of neuronal progenitor cells may thus depend on oxygen density.
Tanaka
Yoshihide
Y
Department of Neurosurgery, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Kanagawa, Japan.
Kanno
Hiroshi
H
Dezawa
Mari
M
Mimura
Toshiro
T
Kubo
Atsuhiko
A
Yamamoto
Isao
I
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D005904:Glial Fibrillary Acidic Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C051774:neurofilament protein H; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein