title: U0126 attenuates ischemia/reperfusion-induced apoptosis and autophagy in myocardium through MEK/ERK/EGR-1 pathway.
abstract: Myocardial ischemia is one of the main causes of sudden cardiac death worldwide. Depending on the cell type and stimulus, ERK activity mediates different anti-proliferative events, such as apoptosis, autophagy, and senescence. The aim of this study was to determine the protective effect of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126), an ERK kinase inhibitor, on myocardial ischemia/reperfusion (I/R) injury and the mechanisms involved. An I/R model was established in vivo in C57BL/6 mice and in vitro using mouse cardiomyocytes, respectively. To evaluate the protective effects of U0126 on I/R injury, we measured the myocardial infarct area, apoptosis, and autophagy. Our data indicated that pretreatment with U0126 significantly reduced the infarct area caused by I/R. Moreover, U0126 reduced the caspase-3 activity and the number of TUNEL-positive cardiomyocytes, which together indicate decreased apoptosis. Additionally, U0126 remarkable reduced the level of Beclin-1 and LC3 and increased p62 expression, which indicates that U0126 suppressed H/R-induced autophagy. Furthermore, the relationship between U0126 and MEK/ERK pathway activation in H/R-induced cardiomyocytes was also investigated. U0126 ameliorated H/R injury through inhibition of the MEK/ERK pathway and by suppressing in the downstream EGR-1 expression. Together, our research suggests that U0126 may protect against H/R injury by preventing H/R-induced myocardium apoptosis and autophagy via the MEK/ERK/EGR-1 pathway, and may be a potential therapeutic approach for attenuating myocardial I/R injury.
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Anxing
authors.initials: A
authors.lastname: Wang
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China. Electronic address: huijunzhangbj@163.com.
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Liang
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Qiu
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Tian
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Junzheng
authors.initials: J
authors.lastname: Jia
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Erke
authors.initials: E
authors.lastname: Xing
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Rufei
authors.initials: R
authors.lastname: Chen
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Zongxing
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: The Second Department of Cardiovascular, Baoji City Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721001, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002070:Butadienes / Q000494:pharmacology* / Q000627:therapeutic use; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002070:Butadienes; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D009570:Nitriles; C113580:U 0126
keywords: EGR-1; Ischemia/reperfusion (I/R); MEK/ERK; Myocardium; U0126