Developmental programming of O2 sensing by neonatal intermittent hypoxia via epigenetic mechanisms |
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Authors: | Jayasri Nanduri Nanduri R Prabhakar |
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Institution: | Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Science Division, University of Chicago, Chicago, USA |
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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 O2 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 Ca2+ 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. |
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Keywords: | Apnea of prematurity Cardio-respiratory morbidities DNA methylation Histone modifications Exocytosis Neurotransmitters/modulators Oxidative stress |
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