Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1α

We report that in Hif1a−/−embryonic stem cells that did not express the O2-regulated HIF-1α subunit, levels of mRNAs encoding glucose transporters and glycolytic enzymes were reduced, and cellular proliferation was impaired

Narayan V. Iyer; Lori E. Kotch; Faton Agani; Sandra W. Leung; Erik Laughner; Roland H. Wenger; Max Gassmann; John D. Gearhart; Ann M. Lawler; Aimee Y. Yu; Gregg L. Semenza


Scholarcy highlights

  • Among the most extensively developed physiologic systems are those devoted to O2 homeostasis, which reflects the human body’s constant and absolute requirement for this essential molecule
  • Recombination results in deletion of Hif1a sequences encoding the bHLH domain, which is essential for dimerization of hypoxia-inducible factor 1␣ with HIF
  • The presence of extensive mesenchymal cell death was confirmed by supravital staining with Nile blue sulfate. These results indicate that mesenchymal cell death was responsible for the failure of neural tube closure that was uniformly observed in Hif1a−/− embryos
  • We have demonstrated recently HIF-1␣ expression in nonhypoxic rat fibroblasts transformed by the V-SRC oncoprotein
  • HIF-1␣ expression may be activated by one or more signal transduction pathways involved in cellular proliferation
  • There was no significant difference in the degree of cell death between genotypes, suggesting that the differences in cell number reflect differences in rates of cell division
  • The decreased proliferation of Hif1a−/− embryonic stem cells suggests that HIF-1␣ may be involved in the regulation of cell division, either directly or indirectly via effects on intermediary metabolism
  • Excessive cell death was detected in E8.5 Hif1a−/− embryos prior to the appearance of any vascular defects, suggesting that an intact mesenchyme may be required to provide essential cellular or humoral support of vascular integrity, as demonstrated in mice deficient for platelet-derived growth factor-B

Need more features? Save interactive summary cards to your Scholarcy Library.