Transcription Factor GATA-4 Is Involved in Erythropoietin-Induced Cardioprotection Against Myocardial Ischemia/Reperfusion Injury

Autor: Shan, Xiaohong, Xu, Xuan, Cao, Bin, Wang, Yongmei, Guo, Lin, Zhu, Quan, Li, Jing, Que, Linli, Chen, Qi, Ha, Tuanzhu, Li, Chuanfu, Li, Yuehua
Předmět:
Zdroj: ETSU Faculty Works.
Druh dokumentu: Text
DOI: 10.1016/j.ijcard.2008.03.043
Popis: Background: Erythropoietin (EPO) can reduce myocardial ischemia/reperfusion (I/R) injury. However, the cellular mechanisms have not been elucidated entirely. The present study was to investigate whether transcription factor GATA-4 could be involved in EPO-induced cardioprotection when it was administered after ischemia, immediately before reperfusion. Methods and results: Male Balb/c mice treated with or without EPO were subjected to ischemia (45 min) followed by reperfusion (4 h). TTC staining showed that the infarct size in EPO-treated mice was significantly reduced compared with untreated I/R mice (P < 0.05). Echocardiography examination suggested that EPO administration significantly improved cardiac function following I/R. TUNEL assay indicated that EPO treatment decreased apoptosis. EPO administration also significantly increased the level of nuclear GATA-4 phosphorylation in the myocardium which was positively correlated with the reduction of myocardial infarction. In vitro hypoxia/re-oxygenation study showed that EPO treatment increased the levels of phospho-GATA-4 and decreased cardiomyocyte apoptosis. More significantly, blocking GATA-4 by transfection of a dominant-negative form of GATA-4 (dnGATA-4) abolished EPO-induced cardioprotective effects. Conclusion: EPO administration after ischemia, just before reperfusion induced cardioprotection and stimulated GATA-4 phosphorylation. Activation of GATA-4 may be one of the mechanisms by which EPO induced protection against myocardial I/R injury.
Databáze: Networked Digital Library of Theses & Dissertations