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Erythropoietin attenuates myocardial ischemia-reperfusion injury aggravated by hyperglycemia which is involved in the upregulation of Bcl-2 through caspase-3 inhibition and GATA-4 regulation
DC Field | Value | Language |
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dc.contributor.author | 전나형 | - |
dc.date.accessioned | 2015-12-24T09:08:44Z | - |
dc.date.available | 2015-12-24T09:08:44Z | - |
dc.date.issued | 2014 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/135060 | - |
dc.description | Dept. of Medicine/박사 | - |
dc.description.abstract | Erythropoietin (EPO), an essential hormone for erythropoiesis, can provide protection against myocardial ischemia/reperfusion (I/R) injury. Hyperglycemia during acute myocardial infarction is common and associated with increased organ damage and attenuated efficacy of protective measures. This study aimed to investigate whether EPO could ameliorate the myocardial I/R injury in hyperglycemic rats as well as in normoglycemic rats. Eighty-two Sprague-Dawley rats were randomly assigned to six groups: normoglycemia (NG)-Sham, NG-I/R–control (IRC), NG-I/R-EPO (IRE), hyperglycemia (HG)-Sham, HG-IRC, and HG-IRE. The rats received 1.2 g/kg dextrose or the 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 infarct size, number of apoptotic cells, and caspase-3 activity compared with untreated I/R rats in hyperglycemic condition. I/R-induced down-regulation of Bcl-2 in myocardium was remarkably attenuated in EPO pretreatment groups under hyperglycemic conditions. EPO administration significantly down-regulated the level of GATA-4 degradation, which was associated with increased stability caused by ERK-regulated GATA-4 post-translational modifications in the myocardium following I/R in hyperglycemic conditions. These results indicate that the protective mechanism of EPO pretreatment before I/R injury involves up-regulation of Bcl-2 via not only down-regulation of caspase-3 activity but also increase of ERK-induced GATA-4 stability in hyperglycemic condition. | - |
dc.description.statementOfResponsibility | open | - |
dc.publisher | Graduate School, Yonsei University | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Erythropoietin attenuates myocardial ischemia-reperfusion injury aggravated by hyperglycemia which is involved in the upregulation of Bcl-2 through caspase-3 inhibition and GATA-4 regulation | - |
dc.title.alternative | Caspase-3 억제와 GATA-4 조절을 통해 bcl-2을 증가시킴으로서 고혈당증에 의해 악화된 심근의 허혈-재관류 손상을 감소시키는 erythropoietin의 효과 | - |
dc.type | Thesis | - |
dc.contributor.alternativeName | Jun, Na Hyung | - |
dc.type.local | Dissertation | - |
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