Original Article
Acta Pharmacologica Sinica (2009) 30: 396–403; doi: 10.1038/aps.2009.2
Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo
Hong-liang Kong1,2,#, Jian-ping Wang3,#, Zhan-quan Li1,#, Shu-mei Zhao4,#, Jing Dong2 and Wei-wei Zhang1
- 1Department of Cardiology, Liaoning Provincial People Hospital, Shenyang l10016, China
- 2Department of Cardiology, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou 450014, China
- 3Department of Neurology, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou 450014, China
- 4College of International education, Shenyang Normal University, Shenyang 110034, China
Correspondence: Dr Hong-liang Kong, E-mail khl339@sina.com
#These authors contributed equally to the article.
Received 28 October 2008; Accepted 5 January 2009; Published online 23 March 2009.
Abstract
Aim:
The aim of this study was to investigate whether Gs-Rbl relieves the CoCl2-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 
mol/L), adenine 9-
-D-arabinofuranoside (ara A, 500 mol/L; AMPK inhibitor) and wortmannin (0.5 mol/L; PI3K inhibitor) only in combination with 200 mol/L Gs-Rbl were administered in hypoxic cardiomyocytes, which were induced by 500 mol/L CoCl2 for 12 h. Then, the apoptotic rate (AR), 2-[3H]-deoxy-D-glucose (2-[3H]-DG) uptake, and the expression of GLUT-4 (including in plasma membrane, PM), phospho-AMPK
(Thr172), AMPK and Akt in cells were assayed.
Results:
Compared with simple hypoxia (0 mol/L Gs-Rbl), Gs-Rb1 greater than 10 mol/L significantly decreased the apoptotic rate (P<0.01) and significantly increased 2-[3H]-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 CoCl2. 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.
Keywords:
neonatal rat cardiomyocytes, hypoxia, apoptosis, ginsenosides-Rbl, glucose transporter-4
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