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Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia.

Authors
 Ji Hae Jun  ;  Na Hyung Jun  ;  Jae Kwang Shim  ;  Eun Jung Shin  ;  Young Lan Kwak 
Citation
 EUROPEAN JOURNAL OF PHARMACOLOGY, Vol.745 : 1-9, 2014 
Journal Title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN
 0014-2999 
Issue Date
2014
MeSH
Acetylation ; Animals ; Apoptosis ; Cardiotonic Agents/administration & dosage ; Cardiotonic Agents/metabolism ; Caspase 3/metabolism ; Cell Line ; Erythropoietin/administration & dosage* ; Erythropoietin/metabolism ; GATA4 Transcription Factor/metabolism ; Hyperglycemia/complications* ; Hyperglycemia/metabolism ; Hyperglycemia/pathology ; MAP Kinase Signaling System/drug effects ; Male ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/pathology ; Myocardial Reperfusion Injury/prevention & control* ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Rats ; Rats, Sprague-Dawley ; Ubiquitination
Keywords
Bcl-2 ; Cardioprotection ; Caspase-3 ; Erythropoietin ; GATA binding protein-4 ; Hyperglycemia
Abstract
Erythropoietin (EPO), an essential hormone for erythropoiesis, provides protection against myocardial ischemia/reperfusion (I/R) injury. Hyperglycemia during acute myocardial infarction aggravates organ damage and attenuates the efficacies of various protective measures. This study aimed to investigate the protective role of EPO against myocardial I/R injury under a clinically relevant moderate hyperglycemic condition and its associated mechanisms. Eighty-two Sprague-Dawley rats were randomly assigned to six groups: normoglycemia-Sham, normoglycemia-I/R-control-saline (IRC), normoglycemia-I/R-EPO (IRE), hyperglycemia-Sham, hyperglycemia-IRC, and hyperglycemia-IRE. The rats received 1.2 g/kg dextrose or same volume of normal saline depending on the group. I/R was induced by a 30 min period of ischemia followed by reperfusion for 4 h. For 1 h before I/R injury, intravenous 4000 IU/kg of EPO was administered. EPO pretreatment significantly reduced the number of apoptotic cells and the infarct size compared with those of the control groups. EPO increased GATA-4 phosphorylation and acetylation against I/R in hyperglycemic myocardium. It also enhanced ERK induced GATA-4 post-translational modifications such as increased GATA-4 phosphorylation and acetylation, and decreased GATA-4 ubiquitination following hypoxia-reoxygenation in H9c2 cells in hyperglycemic medium. Increased GATA-4 stability by EPO diminished I/R-related down-regulation of Bcl-2 and reduction of caspase-3 activities in hyperglycemic myocardium. In conclusion, EPO pretreatment before I/R injury conveyed significant myocardial protection under moderate hyperglycemic condition through mechanisms involved in reduction of caspase-3 activity and up-regulation of Bcl-2 in association with enhanced ERK-induced GATA-4 stability.
Full Text
http://www.sciencedirect.com/science/article/pii/S0014299914006943
DOI
10.1016/j.ejphar.2014.09.038
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kwak, Young Lan(곽영란) ORCID logo https://orcid.org/0000-0002-2984-9927
Shin, Eun Jung(신은정)
Shim, Jae Kwang(심재광) ORCID logo https://orcid.org/0000-0001-9093-9692
Jun, Ji Hae(전지혜) ORCID logo https://orcid.org/0000-0002-8080-0715
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/138474
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