title: Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis.
abstract: OBJECTIVE
  This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis.
  
  
  METHODS
  A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining.
  
  
  RESULTS
  The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05).
  
  
  CONCLUSIONS
  Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy.
authors.affiliation: Department of Pathophysiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: ICU of The Second Hospital, Shanxi Medical University Taiyuan 030001, P. R. China.
authors.forename: Minli
authors.initials: M
authors.lastname: Lv
authors.affiliation: Department of Pathophysiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Jia
authors.affiliation: Functional Integrative Laboratory, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pathophysiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Physiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Xujiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Baohong
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Jingquan
authors.initials: J
authors.lastname: Ji
authors.affiliation: Functional Integrative Laboratory, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Hepatology, Changzhi Medical College Changzhi 046000, P. R. China.
authors.forename: Zhongfu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Institute of Hepatology, Shanxi Medical University Taiyuan 030001, P.R. China.
authors.forename: Dewu
authors.initials: D
authors.lastname: Han
authors.affiliation: USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine, University of Southern California Los Angeles, CA 90033, United States.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053454:Caspase 12 / Q000378:metabolism; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051742:Transcription Factor CHOP / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D051742:Transcription Factor CHOP; D051996:Transcription Factor RelA; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP
keywords: 78 kD glucose-regulated protein; Endotoxin; cardiomyocytes apoptosis; cirrhotic cardiomyopathy; endoplasmic reticulum stress