PMID- 25572699
OWN - NLM
STAT- MEDLINE
DCOM- 20151006
LR  - 20191224
IS  - 1423-0313 (Electronic)
IS  - 0031-7012 (Linking)
VI  - 95
IP  - 1-2
DP  - 2015
TI  - Role of calcium-sensing receptor in cardiac injury of hereditary epileptic rats.
PG  - 10-21
LID - 10.1159/000369627 [doi]
AB  - 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-beta1 (TGF-beta1), 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-beta1, 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-beta1 and CTGF.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Li, Lei
AU  - Li L
AD  - Department of Surgery, Fifth Clinical College of Harbin Medical University, 
      Daqing, China.
FAU - Chen, Fan
AU  - Chen F
FAU - Cao, Yong-Gang
AU  - Cao YG
FAU - Qi, Han-Ping
AU  - Qi HP
FAU - Huang, Wei
AU  - Huang W
FAU - Wang, Ye
AU  - Wang Y
FAU - Jing, Shan
AU  - Jing S
FAU - Sun, Hong-Li
AU  - Sun HL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150108
PL  - Switzerland
TA  - Pharmacology
JT  - Pharmacology
JID - 0152016
RN  - 0 (Bax protein, rat)
RN  - 0 (CCN2 protein, rat)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type II)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - Collagen Type I/metabolism
MH  - Collagen Type II/metabolism
MH  - Connective Tissue Growth Factor/metabolism
MH  - Epilepsy/complications/*metabolism
MH  - Female
MH  - Fibrosis
MH  - Heart Diseases/etiology/*metabolism/pathology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Myocardium/metabolism/pathology
MH  - Myocytes, Cardiac/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats, Wistar
MH  - Receptors, Calcium-Sensing/*metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2015/01/13 06:00
MHDA- 2015/10/07 06:00
CRDT- 2015/01/10 06:00
PHST- 2014/08/26 00:00 [received]
PHST- 2014/11/04 00:00 [accepted]
PHST- 2015/01/10 06:00 [entrez]
PHST- 2015/01/13 06:00 [pubmed]
PHST- 2015/10/07 06:00 [medline]
AID - 000369627 [pii]
AID - 10.1159/000369627 [doi]
PST - ppublish
SO  - Pharmacology. 2015;95(1-2):10-21. doi: 10.1159/000369627. Epub 2015 Jan 8.