title: Transcription factor GATA-4 is involved in erythropoietin-induced cardioprotection against myocardial ischemia/reperfusion injury.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shan
authors.forename: Xuan
authors.initials: X
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Cao
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Linli
authors.initials: L
authors.lastname: Que
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
mesh_terms: 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*
chemical_list: D002316:Cardiotonic Agents; D050991:GATA4 Transcription Factor; D004921:Erythropoietin