| Title | Role of Calcium-Sensing Receptor in Cardiac Injury of Hereditary Epileptic Rats |
| Authors | Li, Lei Chen, Fan Cao, Yong-gang Qi, Han-ping Huang, Wei Wang, Ye Jing, Shan Sun, Hong-li |
| Affiliation | Harbin Med Univ, Clin Coll 5, Dept Surg, Harbin, Peoples R China. Harbin Med Univ, Dept Pharmacol, Daqing, Peoples R China. Peking Univ, Peoples Hosp, Beijing 100044, Peoples R China. |
| Keywords | Epilepsy Calcium-sensing receptor Tremor rat Cardiomyocyte apoptosis Myocardial fibrosis INDUCED APOPTOSIS CORTICAL-NEURONS SUDDEN-DEATH CELL-DEATH KINASE REPERFUSION ISCHEMIA SEIZURES MODEL ARRHYTHMIAS |
| Issue Date | 2015 |
| Publisher | pharmacology |
| Citation | PHARMACOLOGY.2015,95,(1-2),10-21. |
| 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-beta(1) (TGF-beta(1)), 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-beta(1), 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-beta(1) and CTGF. (C) 2015 S. Karger AG, Basel |
| URI | http://hdl.handle.net/20.500.11897/386683 |
| ISSN | 0031-7012 |
| DOI | 10.1159/000369627 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
