Transcription factor GATA-4 is involved in erythropoietin-induced cardioprotection against myocardial ischemia/reperfusion injury.
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.


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.


CONCLUSIONS
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.
Shan
Xiaohong
X
Department of Pathophysiology, Nanjing Medical University, China.
Xu
Xuan
X
Cao
Bin
B
Wang
Yongmei
Y
Guo
Lin
L
Zhu
Quan
Q
Li
Jing
J
Que
Linli
L
Chen
Qi
Q
Ha
Tuanzhu
T
Li
Chuanfu
C
Li
Yuehua
Y
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004921:Erythropoietin / Q000627:therapeutic use*; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*
D002316:Cardiotonic Agents; D050991:GATA4 Transcription Factor; D004921:Erythropoietin