DNA methylation in the central and efferent limbs of the chemoreflex requires carotid body neural activity

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12714-list-0001">The mechanisms underlying long‐term (30 days) intermittent hypoxia (LT‐IH)‐evoked DNA methylation of anti‐oxidant enzyme (AOE) gene repression in the carotid body (CB) reflex pathway were examined.LT‐IH‐treated rats showed increased reactive oxygen species (ROS) levels in the CB reflex pathway.Administration of a ROS scavenger or CB ablation blocked LT‐IH‐evoked DNA methylation and AOE gene repression in the central and efferent limbs of the CB reflex.LT‐IH increased DNA methyltransferase (Dnmt) activity through upregulation of Dnmt1 and 3b proteins by ROS‐dependent inactivation of glycogen synthase kinase 3β (GSK3β) by Akt.A pan‐Akt inhibitor prevented LT‐IH‐induced GSK3β inactivation, elevated Dnmt protein expression and activity, AOE gene methylation, sympathetic activation and hypertension.