title: Role of calcium-sensing receptor in cardiac injury of hereditary epileptic rats.
abstract: BACKGROUND
  It has been reported that epilepsy leads to cardiac injury, but the underlying mechanisms have not yet been elucidated. Studies indicated that the calcium-sensing receptor (CaSR) is involved in cardiomyocyte apoptosis. However, the role of CaSR in epilepsy-induced cardiac injury remains unclear.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of CaSR on cardiac injury of hereditary epileptic rats.
  
  
  METHODS
  The tremor (TRM) rat was used as an epilepsy model. Apoptotic rate, collagen volume fraction, and the expression of CaSR, Bcl-2, Bax, caspase-3, extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), p38 mitogen-activated protein kinase (MAPK), transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen I and collagen III protein were analyzed.
  
  
  RESULTS
  The results showed that the CaSR protein was increased in TRM rat hearts. Cardiac apoptosis and fibrosis were also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Masson's trichrome staining, respectively. Further results demonstrated that the expression of Bax, caspase-3, P-JNK, P-p38, TGF-β1, CTGF, collagen I and collagen III protein were upregulated, whereas Bcl-2 and P-ERK were downregulated in TRM rat hearts. Moreover, these deleterious changes were further aggravated by GdCl3 and attenuated by NPS-2390.
  
  
  CONCLUSIONS
  Our results suggest that CaSR promotes cardiac apoptosis and fibrosis in TRM rat through the induction of mitochondrial and MAPK pathways as well as the activation of TGF-β1 and CTGF.
authors.affiliation: Department of Surgery, Fifth Clinical College of Harbin Medical University, Daqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Cao
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Jing
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004827:Epilepsy / Q000150:complications / Q000378:metabolism*; D005260:Female; D005355:Fibrosis; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C526316:CCN2 protein, rat; D024042:Collagen Type I; D024043:Collagen Type II; D019253:Proto-Oncogene Proteins c-bcl-2; D044169:Receptors, Calcium-Sensing; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D055513:Connective Tissue Growth Factor; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3