Regulation of Gene Expression by HIF-1

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

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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
Publisherwiley
Pages2-14
Number of pages13
ISBN (Electronic)9780470035009
ISBN (Print)0470014571, 9780470014578
DOIs
StatePublished - Oct 7 2008

Keywords

  • 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)

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  • Cite this

    Semenza, G. L., Shimoda, L. A., & Prabhakar, N. R. (2008). Regulation of Gene Expression by HIF-1. In Signalling Pathways in Acute Oxygen Sensing (pp. 2-14). wiley. https://doi.org/10.1002/9780470035009.ch2