title: Increasing expression of (CCAAT enhancer binding protein) homologous protein induced by endoplasmic reticulum stress in myocardium after cardiac arrest and resuscitation in rat.
abstract: OBJECTIVE
  Post-resuscitation myocardial dysfunction yields high rates of mortality, but its potential mechanism remains poorly understood. This study investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis is activated in the heart after cardiac arrest (CA) and resuscitation.
  
  
  METHODS
  Wistar rats were subjected to 5 min electrically induced CA and then resuscitated by mechanical chest compression and epinephrine administration. Animals were decapitated at 3, 6, 12 and 24h (n=8, per group) after return of spontaneous circulation (ROSC). Myocardial specimens were analysed using electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, reverse transcription polymerase chain reaction, Western blotting and immunohistochemistry.
  
  
  RESULTS
  The ER, mitochondria and nuclei in cardiomyocytes from the experimental groups were seriously damaged. Typical apoptotic nuclei were observed in cardiomyocytes 24h after resuscitation. TUNEL showed an approximately two-fold increase in the percentage of apoptotic cardiomyocytes 24h post-ROSC. The mRNA levels of glucose-regulated protein78 (GRP78) and calreticulin (CRT) were significantly elevated 3-24h after reperfusion. The transcription of the ER stress-associated apoptotic gene chop increased. The protein expressions of GRP78 and CRT were up-regulated at first; the C/EBP (CCAAT enhancer binding protein) homologous protein (CHOP) then increased, along with elevations in the active form of caspase-3. In situ immunostaining of ER stress markers also demonstrated that ER stress occurred in the myocardium after CA and resuscitation.
  
  
  CONCLUSIONS
  ER stress and the CHOP apoptotic pathway are activated in the myocardium after CA and resuscitation. ER stress-mediated apoptosis may be one of the main pathological mechanisms of post-resuscitation myocardial injury.
authors.affiliation: Department of Emergency, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xue-lian
authors.initials: XL
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D053148:Caspase 3 / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006323:Heart Arrest / Q000378:metabolism* / Q000628:therapy*; D006360:Heat-Shock Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D015415:Biomarkers; D022762:CCAAT-Enhancer-Binding Proteins; D037282:Calreticulin; D053148:Caspase 3; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP