Regulation of Gene Expression by HIF-1

Gregg L. Semenza, Larissa A. Shimoda, Nanduri R. Prabhakar

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


Hypoxia-inducible factor 1 (HIF-1) is a critical mediator of physiological responses to acute and chronic hypoxia. First, HIF-1 is required for the development of the systems that mediate these responses, including the heart, blood and blood vessels. Mice with complete HIF-1α deficiency manifest developmental defects that involve all three components of the circulatory system. Second, HIF-1 mediates changes in gene expression that underlie physiological responses to chronic hypoxia, such as increased erythropoiesis and angiogenesis. Hif1a+/- mice, which are partially HIF-1α deficient, manifest impaired hypoxia-induced pulmonary vascular remodelling. Smooth muscle cells from pulmonary arteries (PASMCs) of wild-type mice subjected to chronic hypoxia manifest hypertrophy, depolarization, increased [Ca22+]i, and decreased voltage-gated K+ currents. These responses are impaired in PASMCs from Hif1a+/- mice. Carotid bodies isolated from Hif1a+/- mice are unresponsive to hypoxia despite normal histology and normal responses to cyanide stimulation. Rat PC12 cells share properties with O2-sensing glomus cells of the carotid body, including hypoxia-inducible expression of tyrosine hydroxylase, the rate limiting enzyme for catecholamine biosynthesis. In PC12 cells subjected to intermittent hypoxia, Ca2+/calmodulin-dependent kinase activity leads to HIF-1 transcriptional activity and tyrosine hydroxylase mRNA expression. Thus, HIF-1 regulates both acute and chronic responses to continuous and intermittent hypoxia.

Original languageEnglish (US)
Title of host publicationSignalling Pathways in Acute Oxygen Sensing
Number of pages13
ISBN (Electronic)9780470035009
ISBN (Print)0470014571, 9780470014578
StatePublished - Oct 7 2008


  • HIF-1 gene regulation
  • HIF-1 induced by intermittent hypoxia
  • Hypoxia response element (HRE)
  • Hypoxia-inducible factor 1 (HIF-1)
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Regulation of Gene Expression by HIF-1'. Together they form a unique fingerprint.

Cite this