Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia

Ji Hae Jun, Na Hyung Jun, Jae Kwang Shim, Eun Jung Shin, Younglan Kwak

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalEuropean Journal of Pharmacology
Volume745
DOIs
Publication statusPublished - 2014 Dec 15

Fingerprint

Erythropoietin
Reperfusion Injury
Hyperglycemia
Myocardium
Reperfusion
Ischemia
Myocardial Reperfusion Injury
Acetylation
Caspase 3
Myocardial Ischemia
Phosphorylation
Erythropoiesis
Ubiquitination
Post Translational Protein Processing
Cell Size
Sprague Dawley Rats
Up-Regulation
Down-Regulation
Myocardial Infarction
Hormones

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Jun, Ji Hae ; Jun, Na Hyung ; Shim, Jae Kwang ; Shin, Eun Jung ; Kwak, Younglan. / Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia. In: European Journal of Pharmacology. 2014 ; Vol. 745. pp. 1-9.
@article{ce87f4faca434e189706e0a3e724ad08,
title = "Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate 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.",
author = "Jun, {Ji Hae} and Jun, {Na Hyung} and Shim, {Jae Kwang} and Shin, {Eun Jung} and Younglan Kwak",
year = "2014",
month = "12",
day = "15",
doi = "10.1016/j.ejphar.2014.09.038",
language = "English",
volume = "745",
pages = "1--9",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia. / Jun, Ji Hae; Jun, Na Hyung; Shim, Jae Kwang; Shin, Eun Jung; Kwak, Younglan.

In: European Journal of Pharmacology, Vol. 745, 15.12.2014, p. 1-9.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia

AU - Jun, Ji Hae

AU - Jun, Na Hyung

AU - Shim, Jae Kwang

AU - Shin, Eun Jung

AU - Kwak, Younglan

PY - 2014/12/15

Y1 - 2014/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84918822859&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918822859&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2014.09.038

DO - 10.1016/j.ejphar.2014.09.038

M3 - Article

C2 - 25446919

AN - SCOPUS:84918822859

VL - 745

SP - 1

EP - 9

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -