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Epigenetic Regulation of Carotid Body Oxygen Sensing: Clinical Implications

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Arterial Chemoreceptors in Physiology and Pathophysiology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 860))

Abstract

Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in infants born preterm. Recent epidemiological studies showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension. Thus, apnea of prematurity predisposes individuals to autonomic dysfunction in adulthood. Experimental studies showed that adult rats exposed to IH as neonates exhibit augmented carotid body and adrenal chromaffin cells (AMC) response to hypoxia and irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity of the carotid body and AMC in adult rats exposed to neonatal IH was associated with increased oxidative stress, decreased expression of genes encoding anti-oxidant enzymes, and increased expression of pro-oxidant enzymes. Epigenetic mechanisms including DNA methylation leads to long-term changes in gene expression. The decreased expression of the Sod2 gene, which encodes the anti-oxidant enzyme, superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during IH exposure prevented the oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction in adult rats. These findings suggest that epigenetic mechanisms, especially DNA methylation contributes to neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.

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Acknowledgement

This research was supported by grants from National Institutes of Health, Heart, Lung and Blood Institute PO1-HL-90554 and UH2- HL-123610.

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Authors and Affiliations

  1. Biological Science Division, Institute for Integrative Physiology, 5841 S. Maryland Avenue, MC 5068, Room N-711, University of Chicago, Chicago, IL, 60637, USA

    Jayasri Nanduri

  2. Biological Science Division, Institute for Integrative Physiology and Center for Systems Biology of O(2) Sensing, University of Chicago, Chicago, IL, USA

    Nanduri R. Prabhakar

Authors
  1. Jayasri Nanduri
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  2. Nanduri R. Prabhakar
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Correspondence to Nanduri R. Prabhakar .

Editor information

Editors and Affiliations

  1. Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Faculty of Medicine and Health, Leeds, United Kingdom

    Chris Peers

  2. College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

    Prem Kumar

  3. Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, Ohio, USA

    Christopher Wyatt

  4. Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    Estelle Gauda

  5. Department of Biology, McMaster University, Hamilton, Ontario, Canada

    Colin A. Nurse

  6. Institute for Integrative Physiology and Center for Systems Biology of O(2) Sensing Biological Sciences Division, University of Chicago, Chicago, Illinois, USA

    Nanduri Prabhakar

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Nanduri, J., Prabhakar, N.R. (2015). Epigenetic Regulation of Carotid Body Oxygen Sensing: Clinical Implications. In: Peers, C., Kumar, P., Wyatt, C., Gauda, E., Nurse, C., Prabhakar, N. (eds) Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology, vol 860. Springer, Cham. https://doi.org/10.1007/978-3-319-18440-1_1

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