The role of hypoxia-inducible factors in oxygen sensing by the carotid body

Adv Exp Med Biol. 2012;758:1-5. doi: 10.1007/978-94-007-4584-1_1.

Abstract

Chronic intermittent hypoxia (IH) associated with sleep-disordered breathing is an important cause of hypertension, which results from carotid body-mediated activation of the sympathetic nervous system. IH triggers increased levels of reactive oxygen species (ROS) in the carotid body, which induce increased synthesis and stability of hypoxia-inducible factor 1α (HIF-1α) and calpain-dependent degradation of HIF-2α. HIF-1 activates transcription of the Nox2 gene, encoding NADPH oxidase 2, which generates superoxide. Loss of HIF-2 activity leads to decreased transcription of the Sod2 gene, encoding manganese superoxide dismutase, which converts superoxide to hydrogen peroxide. Thus, IH disrupts the balance between HIF-1-dependent pro-oxidant and HIF-2-dependent anti-oxidant activities, and this loss of redox homeostasis underlies the pathogenesis of autonomic morbidities associated with IH.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Carotid Body / physiology*
  • Homeostasis
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
  • Oxygen / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species
  • endothelial PAS domain-containing protein 1
  • Oxygen