AUTHOR=Lu Shishi , Zhang Yanmei , Zhong Shuping , Gao Fenfei , Chen Yicun , Li Weiqiu , Zheng Fuchun , Shi Ganggang TITLE=N-n-butyl Haloperidol Iodide Protects against Hypoxia/Reoxygenation Injury in Cardiac Microvascular Endothelial Cells by Regulating the ROS/MAPK/Egr-1 Pathway JOURNAL=Frontiers in Pharmacology VOLUME=7 YEAR=2017 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00520 DOI=10.3389/fphar.2016.00520 ISSN=1663-9812 ABSTRACT=
Endothelium dysfunction induced by reactive oxygen species (ROS) is an important initial event at the onset of myocardial ischemia/reperfusion in which the Egr-1 transcription factor often serves as a master switch for various damage pathways following reperfusion injury. We hypothesized that an intracellular ROS/MAPK/Egr-1 signaling pathway is activated in cardiac microvascular endothelial cells (CMECs) following hypoxia/reoxygenation (H/R). ROS generation, by either H/R or the ROS donor xanthine oxidase-hypoxanthine (XO/HX) activated all three MAPKs (ERK1/2, JNK, p38), and induced Egr-1 expression and Egr-1 DNA-binding activity in CMECs, whereas ROS scavengers (EDA and NAC) had the opposite effect following H/R. Inhibitors of all three MAPKs individually inhibited induction of Egr-1 expression by H/R in CMECs. Moreover,