title: Egr-1, a central and unifying role in cardioprotection from ischemia-reperfusion injury?
abstract: OBJECTIVE
  Our previous studies have shown that N-n-butyl haloperidol iodide (F(2)) can antagonize myocardial ischemia/reperfusion (I/R) injury by blocking intracellular Ca(2+) overload and suppressing Egr-1 overexpression. The present study is to investigate the relation between the reduction of Ca(2+) overload and the inhibition of Egr-1 overexpression.
  
  
  METHODS
  The Sprague-Dawley rat myocardial I/R model and cultured cardiomyocyte hypoxia-reoxygenation (H/R) model were established. Administration of Egr-1 antisense oligodeoxyribonucleotide (AS-ODN) only or combining with F(2), Egr-1 protein expression was examined by Western-blot analyses. Hemodynamic parameters, creatine kinase (CK) and lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), myeloperoxidase (MPO), cardiac troponin I (cTnI), and tumor necrosis factor-alpha (TNF-alpha) were measured to assess the degree of injury and inflammation of myocardial tissues and cells.
  
  
  RESULTS
  Treatment with Egr-1 AS-ODN significantly reduced Egr-1 protein expression and attenuated injury and inflammation of myocardium caused by I/R or H/R evidenced by the amelioration of hemodynamics, the decrease in leakage of CK, LDH, cTnI, the increase in MDA generation, the decrease in SOD activity, the reduction of MPO activity in myocardial tissues and release of TNF-alpha from cultured cardiomyocytes. Treatment with F(2) combined with Egr-1 AS-ODN, the inhibition of Egr-1 protein expression and inflammation (MPO activity and TNF-alpha level) were not enhanced, but the protection from myocardial I/R (or H/R) injury was significantly increased in hemodynamics and cytomembrane permeability relative to the using of Egr-1 AS-ODN only.
  
  
  CONCLUSIONS
  These data suggest that the inhibition of Egr-1 overexpression cannot involve all mechanisms of cardioprotection from I/R injury.
authors.affiliation: Department of Pharmacology, First Affiliated Hospital, Shantou University Medical College, China.
authors.forename: Fen-Fei
authors.initials: FF
authors.lastname: Gao
authors.forename: Qiang-Yong
authors.initials: QY
authors.lastname: Jia
authors.forename: Fu-Xiao
authors.initials: FX
authors.lastname: Guo
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Zhang
authors.forename: Zhan-Qin
authors.initials: ZQ
authors.lastname: Huang
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhou
authors.forename: Yi-Cun
authors.initials: YC
authors.lastname: Chen
authors.forename: Gang-Gang
authors.initials: GG
authors.lastname: Shi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006439:Hemodynamics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; D020319:Oligodeoxyribonucleotides, Antisense; D017382:Reactive Oxygen Species; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D002118:Calcium