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

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

SUBMITTER: Roitbak T 

PROVIDER: S-EPMC3629813 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature