title: Novel distribution of calreticulin to cardiomyocyte mitochondria and its increase in a rat model of dilated cardiomyopathy.
abstract: BACKGROUND
  Calreticulin (CRT), a Ca(2+)-binding chaperone of the endoplasmic reticulum, can also be found in several other locations including the cytosol, nucleus, secretory granules, the outer side of the plasma membrane, and the extracellular matrix. Whether CRT is localized at mitochondria of cardiomyocytes and whether such localization is affected under DCM are still unclear.
  
  
  RESULTS
  The DCM model was generated in rats by the daily oral administration of furazolidone for thirty weeks. Echocardiographic and hemodynamic studies demonstrated enlarged left ventricular dimensions and reduced systolic and diastolic function in DCM rats. Immuno-electron microscopy and Western blot showed that CRT was present in cardiomyocyte mitochondria and the mitochondrial content of CRT was increased in DCM hearts (P<0.05). Morphometric analysis showed notable myocardial apoptosis and mitochondrial swelling with fractured or dissolved cristae in the DCM hearts. Compared with the control group, the mitochondrial membrane potential level of the freshly isolated cardiac mitochondria and the enzyme activities of cytochrome c oxidase and succinate dehydrogenase in the model group were significantly decreased (P<0.05), and the myocardial apoptosis index and the caspase activities of caspase-9 and caspase-3 were significantly increased (P<0.05). Pearson linear correlation analysis showed that the mitochondrial content of CRT had negative correlations with the mitochondrial function, and a positive correlation with myocardial apoptosis index (P<0.001). The protein expression level of cytochrome c and the phosphorylation activity of STAT3 in the mitochondrial fraction were significantly decreased in the model group compared with the control group (P<0.05).
  
  
  CONCLUSIONS
  These data demonstrate that CRT is localized at cardiomyocyte mitochondria and its mitochondrial content is increased in DCM hearts.
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: weijindr@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Shan
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Respiratory Medicine, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Xue
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology*; D032342:Muscle Cells / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D037282:Calreticulin
keywords: Apoptosis; Calreticulin; Dilated cardiomyopathy; Mitochondria; STAT3