title: Effects of calcium-sensing receptors on apoptosis in rat hippocampus during hypoxia/reoxygenation through the ERK1/2 pathway.
abstract: OBJECTIVE
  To explore the effects of calcium-sensing receptors (CaSR) on apoptosis in rat hippocampus during hypoxia/reoxygenation (H/R).
  
  
  METHODS
  After rat hippocampus was isolated, the cultures were subjected to H/R, and meanwhile gadolinium chloride (GdCl3, agonist of CaSR) and NPS 2390 (antagonists of CaSR) were added to reperfusion solution. The number of hippocampal neuron, cell viability and apoptosis rate were determined by inverted microscope, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometer (FCM), respectively. Besides, caspase-3, Bax, cytochrome C (Cyt-c), extracellular signal-regulated protein kinase (ERK) 1/2, pERK1/2, P38 and pP38 were analyzed by Western blotting.
  
  
  RESULTS
  The hippocampal neuron number and cell viability were significantly decreased during H/R, and were further significantly reduced when co-treatment with CaSR agonist GdCl3. But the effects of GdCl3 were attenuated by NPS-2390. Whereas, apoptosis rate, the expression level of caspase-3, Bax and Cyt-c were all significantly increased under H/R condition, and was further significantly increased by GdCl3, but were reversed by NPS-2390 (P < 0.05). Moreover, there were no significant differences in expression of ERK1/2, P38 and pP38 among different groups. However, the expression of pERK1/2 was significantly increased during H/R, but was significantly reduced by NPS 2390 (P < 0.05).
  
  
  CONCLUSIONS
  The results suggest that CaSR might play significant roles in the induction of hippocampus apoptosis in rat during H/R through phosphorylation of ERK1/2.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China.
authors.forename: Shilei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D011810:Quinoxalines / Q000494:pharmacology; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C569355:2-quinoxaline-carboxamide-N-adamantan-1-yl; D051017:Apoptosis Regulatory Proteins; D011810:Quinoxalines; D044169:Receptors, Calcium-Sensing; C473605:extracellular calcium cation-sensing receptor, rat; D005682:Gadolinium; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C038958:gadolinium chloride; D000218:Adamantane
keywords: Calcium-sensing receptors; GdCl3; NPS 2390; apoptosis; hippocampus; hypoxia/reoxygenation