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Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia.
MedLine Citation:
PMID:  25446919     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 1.2g/kg dextrose or same volume of normal saline depending on the group. I/R was induced by a 30min period of ischemia followed by reperfusion for 4h. For 1h before I/R injury, intravenous 4000IU/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.
Authors:
Ji Hae Jun; Na-Hyung Jun; Jae-Kwang Shim; Eun Jung Shin; Young-Lan Kwak
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-16
Journal Detail:
Title:  European journal of pharmacology     Volume:  745C     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-9     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier B.V. All rights reserved.
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