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The Role of Hypoxia-Inducible Factors in Oxygen Sensing by the Carotid Body

  • Gregg L. SemenzaEmail author
  • Nanduri R. Prabhakar
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)

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.

Keywords

Cardiorespiratory homeostasis Obstructive sleep apnea Oxidative stress Oxygen homeostasis 

Notes

Acknowledgements

Research from authors’ laboratories was supported by contracts/grants HHS-N268201000032C, PO1-HL65608, P20-GM78494, RO1-HL55338, U54-CA143868 (G.L.S.) and HL-76537, HL-90554, and HL-86493 (N.R.P) from the National Institutes of Health.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology; and McKusick-Nathans Institute of Genetic MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences DivisionUniversity of ChicagoChicagoUSA

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