title: N-n-butyl haloperidol iodide protects cardiac microvascular endothelial cells from hypoxia/reoxygenation injury by down-regulating Egr-1 expression.
abstract: OBJECTIVE
  Our previous studies have shown that N-n-butyl haloperidol iodide (F2) can antagonize myocardial ischemia/reperfusion (I/R) injury by down-regulating the early growth response (Egr)-1 expression, but the molecular mechanisms are not well understood. Because there is evidence implicating myocardial I/R injury is closely associated with endothelial dysfunction. The present study is to test the hypothesis that the protective effects of F2 on myocardial I/R injury is related closely with down-regulating Egr-1 expression on cardiac microvascular endothelial cells (CMECs).
  
  
  METHODS
  A model of cultured CMECs exposed to hypoxia/reoxygenation (H/R) was developed. With antisense Egr-1 oligodeoxyribonucleotide (ODN), the relationship between Egr-1 expression and endothelial H/R injury was investigated. Egr-1 mRNA and protein expression were examined by real-time fluorescent quantitative PCR, immunocytochemical staining and Western-blot analysis. Lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), intercellular adhesion molecule-1 (ICAM-1), adherence of neutrophil and platelets, and cell viability were measured after H/R to evaluate the degree of endothelial injury.
  
  
  RESULTS
  Pretreatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of CMECs. Consistent with down-regulation of Egr-1 expression by F2, inflammation and other damage were significantly reduced as evidenced by a decrease of ICAM-1 expression, reduction of neutrophil and platelets adherence, increase in SOD, and decreases in MDA and LDH levels, resulting in the rise of cell viability.
  
  
  CONCLUSIONS
  We demonstrate a protective effect of F2 in CMECs against H/R injury by down-regulating Egr-1 expression, which might be play a vital role in the pathogenesis of myocardial I/R injury.
authors.affiliation: Department of Pharmacology, Shantou University Medical College, Shantou, PR China.
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fenfei
authors.initials: F
authors.lastname: Gao
authors.forename: Fuxiao
authors.initials: F
authors.lastname: Guo
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Cai
authors.forename: Yicun
authors.initials: Y
authors.lastname: Chen
authors.forename: Jinhong
authors.initials: J
authors.lastname: Zheng
authors.forename: Ganggang
authors.initials: G
authors.lastname: Shi
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; C482574:N-n-butyl haloperidol iodide; D020319:Oligodeoxyribonucleotides, Antisense; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D006220:Haloperidol