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Cell Mol Neurobiol. 2011 Jan;31(1):119-33. doi: 10.1007/s10571-010-9561-5. Epub 2010 Sep 16.

Continuous expression of HIF-1α in neural stem/progenitor cells.

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  • 1Department of Neurosurgery, University of New Mexico Health Sciences Center, Albuquerque, 87131-0001, USA. troitbak@salud.unm.edu

Abstract

Hypoxia-inducible factor-1 alpha subunit (HIF-1α) is a transcriptional activator mediating adaptive cellular response to hypoxia. Normally degraded in most cell types and tissues, HIF-1α becomes stable and transcriptionally active under conditions of hypoxia. In contrast, we found that HIF-1α is continuously expressed in adult brain neurogenic zones, as well as in neural stem/progenitor cells (NSPCs) from the embryonic and post-natal mouse brain. Our in vitro studies suggest that HIF-1α does not undergo typical hydroxylation, ubiquitination, and degradation within NSPCs under normoxic conditions. Based on immunofluorescence and cell fractionation, HIF-1α is primarily sequestered in membranous cytoplasmic structures, identified by immuno-electron microscopy as HIF-1α-bearing vesicles (HBV), which may prevent HIF-1α from degradation within the cytoplasm. HIF-1α shRNAi-mediated knockdown reduced the resistance of NSPCs to hypoxia, and markedly altered the expression levels of Notch-1 and β-catenin, which influence NSPC differentiation. These findings indicate a unique regulation of HIF-1α protein stability in NSPCs, which may have importance in NSPCs properties and function.

PMID:
20844947
[PubMed - indexed for MEDLINE]
PMCID:
PMC3629813
Free PMC Article
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