title: Developmental programming of O(2) sensing by neonatal intermittent hypoxia via epigenetic mechanisms.
abstract: Recurrent apnea with intermittent hypoxia (IH) is a major clinical problem in infants born preterm. Carotid body chemo-reflex and catecholamine secretion from adrenal medullary chromaffin cells (AMC) are important for maintenance of cardio-respiratory homeostasis during hypoxia. This article highlights studies on the effects of IH on O(2) sensing by the carotid body and AMC in neonatal rodents. Neonatal IH augments hypoxia-evoked carotid body sensory excitation and catecholamine secretion from AMC which are mediated by reactive oxygen species (ROS)-dependent recruitment of endothelin-1 and Ca(2+) signaling, respectively. The effects of neonatal IH persist into adulthood. Evidence is emerging that neonatal IH initiates epigenetic mechanisms involving DNA hypermethylation contributing to long-lasting increase in ROS levels. Since adult human subjects born preterm exhibit higher incidence of sleep-disordered breathing and hypertension, DNA hypomethylating agents might offer a novel therapeutic intervention to decrease long-term cardio-respiratory morbidity caused by neonatal IH.
authors: Institute for Integrative Physiology and Center for Systems Biology of O(2) Sensing, Biological Science Division, University of Chicago, Chicago, USA.
authors: Jayasri
authors: J
authors: Nanduri
authors: Nanduri R
authors: NR
authors: Prabhakar
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002344:Carotid Body / Q000502:physiology*; D019439:Chromaffin Cells / Q000502:physiology*; D044127:Epigenesis, Genetic; D005311:Fetal Hypoxia / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D010100:Oxygen / Q000097:blood*
chemical_list: D010100:Oxygen