title: Effects of Panax quinquefolium saponin on phosphatidylinositol 3-kinase/serine threonine kinase pathway of neonatal rat myocardial cells subjected to hypoxia.
abstract: OBJECTIVE
  To explore the effects of Panax Quinquefolium Saponin (PQS) on phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/Akt) pathway of neonatal rat myocardial cells subjected to hypoxia.
  
  
  METHODS
  Neonatal rat myocardial cells were cultured in vitro. After the myocardial cell injury was induced by hypoxia, the cells were randomized into 5 groups: the normal group, the model group, the positive control group (Ciclosporin A, 2 µ mol/L), the low-dose PQS group (PQSL, 25mg/L), and the high-dose PQS group (PQSH, 50 mg/L). Morphology and behavior of myocardial cells were observed under an inverted microscope. Apoptosis rate and lactate dehydrogenase (LDH) leakage rate of myocardial cells were determined by colorimetry. Mitochondrial transmembrane potential was assessed using a fluorexon laser. Phospho-glycogen synthase kinase (GSK)-3β and phospho-Akt as well as cytochrome C were determined by Western blot
  
  
  RESULTS
  LDH leakage in the Ciclosporin A group, PQSH group and PQSL group reduced progressively compared with the model group (P<0.05). Akt and GSK-3β was strongly phosphorylated after treatment with Ciclosporin A and PQS compared with the model group (P<0.05, P<0.01). Compared with the model group (16.41±1.74; 35.28±6.30), both the integrated optical density of mitochondrial permeability transition pore (MPTP) and the mitochondrial transmembrane potential significantly increased in the PQSH group (42.74±2.12; 71.36±6.54) and the PQSL group (39.58±1.49; 66.99±5.45; P<0.05, P<0.01). However, the protein of cytochrome C outside the mitochondrion decreased in the PQSH group (273.66±14.61) and the PQSL group (259.62±17.31) compared with the model group (502.41±17.76; P<0.05).
  
  
  CONCLUSIONS
  Through activation of the PI3K/Akt pathway and inhibition of the MPTP, PQS might protect the heart against ischemia injury and apoptosis of myocardial cells.
authors.affiliation: Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
authors.forename: Chun-yu
authors.initials: CY
authors.lastname: Guo
authors.forename: Xiao-juan
authors.initials: XJ
authors.lastname: Ma
authors.forename: Jing-shang
authors.initials: JS
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Hui-jun
authors.initials: HJ
authors.lastname: Yin
authors.forename: Ke-ji
authors.initials: KJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007770:L-Lactate Dehydrogenase; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D012503:Saponins; C079995:Panax quinquefolium saponin; C000605508:Gsk3b protein, rat