title: Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo.
abstract: OBJECTIVE
  The aim of this study was to investigate whether Gs-Rbl relieves the CoCl(2)-induced apoptosis of hypoxic neonatal rat cardiomyocytes and in which the role of glucose transporter-4 (GLUT-4).
  
  
  METHODS
  Gs-Rbl (0, 10, 50, 100, 200, 400, and 500 micromol/L), adenine 9-beta-D-arabinofuranoside (ara A, 500 micromol/L; AMPK inhibitor) and wortmannin (0.5 micromol/L; PI3K inhibitor) only in combination with 200 micromol/L Gs-Rbl were administered in hypoxic cardiomyocytes, which were induced by 500 micromol/L CoCl(2) for 12 h. Then, the apoptotic rate (AR), 2-[(3)H]-deoxy-D-glucose (2-[(3)H]-DG) uptake, and the expression of GLUT-4 (including in plasma membrane, PM), phospho-AMPKalpha (Thr172), AMPKalpha and Akt in cells were assayed.
  
  
  RESULTS
  Compared with simple hypoxia (0 micromol/L Gs-Rbl), Gs-Rb1 greater than 10 micromol/L significantly decreased the apoptotic rate (P<0.01) and significantly increased 2-[(3)H]-DG uptake (P<0.01), GLUT-4 content in cells and PM (P<0.01), AMPK activity (P<0.01) and Akt (P<0.01) levels in a dose-dependent manner. AMPK activity was completely suppressed by ara-A, just as Akt was suppressed by wortmannin. The AR, glucose uptake and GLUT-4 levels in cells and PM were partly down-regulated by ara-A or wortmannin.
  
  
  CONCLUSIONS
  Gs-Rb1 may protect neonatal rat cardiomyocytes from apoptosis induced by CoCl(2). The anti-apoptotic effect of Gs-Rb1 may occur by improving glucose uptake, in which GLUT-4 translocation and expression played a key role. Both the AMPK and the PI3K/Akt pathways may take part in the anti-hypoxic efficacy of Gs-Rb1.
authors.affiliation: Department of Cardiology, Liaoning Provincial People Hospital, Shenyang, China. khl339@sina.com
authors.forename: Hong-liang
authors.initials: HL
authors.lastname: Kong
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Zhan-quan
authors.initials: ZQ
authors.lastname: Li
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Zhang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D036145:Ginsenosides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000032:analysis / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D036145:Ginsenosides; D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; C442759:ginsenoside Rb1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase; D005947:Glucose