title: Activation of calcium-sensing receptors is associated with apoptosis in a model of simulated cardiomyocytes ischemia/reperfusion.
abstract: OBJECTIVE
  Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation. Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP3 signaling transduction. However, little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes.
  
  
  METHODS
  Primary neonatal rat ventricular cardiomyocytes were incubated in ischemiamimetic solution for 2 h, and then re-incubated in normal culture medium for 24 h to establish a model of simulated ischemia/reperfusion (I/R). Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The expression of CaSRs mRNA was detected by real-time reverse transcription polymerase chain reaction (RT-PCR). In addition, the expressions of caspase-3 and Bcl-2 were analyzed by western blot.
  
  
  RESULTS
  The simulated I/R enhanced the expression of CaSRs and cardiomyocyte apoptosis. GdCl3, a specific activator of CaSRs, further increased the expression of CaSRs and cardiomyocyte apoptosis, along with up-regulation of caspase-3 and down-regulation of Bcl-2.
  
  
  CONCLUSIONS
  CaSRs are associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Tiebing
authors.initials: T
authors.lastname: Zhu
authors.forename: Tingting
authors.initials: T
authors.lastname: Sun
authors.forename: Liansheng
authors.initials: L
authors.lastname: Wang
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.forename: Zhengxian
authors.initials: Z
authors.lastname: Tao
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
keywords: apoptosis; calcium sensing receptors; cardiomyocyte; ischemia/reperfusion
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