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, N-n-butyl haloperidol (F2), previously shown to protect cardiomyocytes subjected to I/R, dose-dependently downregulated H/R-induced ROS generation, MAPK activation, and Egr-1 expression and activity in CMECs, whereas XO/HX and MAPK activators (EGF, anisomycin) antagonized the effects of F2. Inhibition of the ROS/MAPK/Egr-1 signaling pathway, by either F2, NAC, or inhibition of MAPK, increased CMEC viability and the GSH/GSSG ratio, and decreased Egr-1 nuclear translocation. These results show that the ROS/MAPK/Egr-1 signaling pathway mediates H/R injury in CMECs, and F2 blocks this pathway to protect against H/R injury and further alleviate myocardial I/R injury.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Lu S,Zhang Y,Zhong S,Gao F,Chen Y,Li W,Zheng F,Shi Gdoi
10.3389/fphar.2016.00520subject
Has Abstractpub_date
2017-01-05 00:00:00pages
520issn
1663-9812journal_volume
7pub_type
杂志文章abstract::Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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pub_type: 杂志文章
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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pub_type: 杂志文章,收录出版
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