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  • Title: Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo.
    Author: Kong HL, Wang JP, Li ZQ, Zhao SM, Dong J, Zhang WW.
    Journal: Acta Pharmacol Sin; 2009 Apr; 30(4):396-403. PubMed ID: 19305424.
    Abstract:
    AIM: 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. CONCLUSION: 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.
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