title: Lipopolysaccharide pretreatment attenuates myocardial infarct size: A possible mechanism involving heat shock protein 70-inhibitory kappaBalpha complex and attenuation of nuclear factor kappaB.
abstract: OBJECTIVE
  Lipopolysaccharide pretreatment is known to reduce myocardial infarct size, but the mechanism has not been elucidated. We hypothesized that heat shock protein 70, induced by lipopolysaccharide pretreatment, formed complexes with inhibitory kappaBalpha, thereby inhibiting degradation and attenuating activation of nuclear factor kappaB and cellular injury in rat myocardium.
  
  
  METHODS
  Fifteen Sprague-Dawley rats were given saline solution (control group) or lipopolysaccharide. After 48 hours, 5 hearts in each group were excised without ischemia for examination of heat shock protein 70 and inhibitory kappaBalpha levels and detection of heat shock protein 70-inhibitory kappaBalpha complexes. Myocardium from the remaining 10 rats in each group was exposed to 30 minutes of ischemia and 30 minutes of reperfusion (n = 5) to evaluate nuclear factor kappaB activity or to 24 hours of reperfusion (n = 5) to evaluate infarct size.
  
  
  RESULTS
  Infarct size was reduced in the lipopolysaccharide group (P <.05). Nuclear factor kappaB was activated in the control ischemia group and attenuated in the lipopolysaccharide group (P <.05). Heat shock protein 70 levels were increased in the lipopolysaccharide group (P <.05), but inhibitory kappaBalpha levels were similar in both groups. Heat shock protein 70-inhibitory kappaBalpha complexes were detected only in the lipopolysaccharide group. Colocalization of the 2 proteins was observed in the lipopolysaccharide group.
  
  
  CONCLUSIONS
  Heat shock protein 70, induced by lipopolysaccharide pretreatment, forms complexes with inhibitory kappaBalpha and attenuates activation of nuclear factor kappaB and myocardial infarct size. Our results suggest that attenuation of nuclear factor kappaB through a mechanism forming heat shock protein 70-inhibitory kappaBalpha complexes might protect the myocardium from ischemia-reperfusion injury.
authors.affiliation: Divisions of Cardiothoracic Surgery and Biochemical Genetics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shimizu
authors.forename: Mimi
authors.initials: M
authors.lastname: Tamamori-Adachi
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Arai
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tabuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamori
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018840:HSP70 Heat-Shock Proteins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha