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Epigenetic Regulation of Carotid Body Oxygen Sensing: Clinical Implications

  • Jayasri Nanduri
  • Nanduri R. PrabhakarEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

O2 sensing Apnea Epigenetic mechanisms DNA hypermethylation Exocytosis Oxidative stress 

Notes

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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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Biological Science DivisionInstitute for Integrative PhysiologyChicagoUSA
  2. 2.Biological Science DivisionInstitute for Integrative Physiology and Center for Systems Biology of O(2) Sensing, University of ChicagoChicagoUSA

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