Acta Pharmacologica Sinica (2009) 30: 396-403; doi: 10.1038/aps.2009.2; published online 23rd March 2009

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 µmol/L), adenine 9-β-D-arabinofuranoside (ara A, 500 µmol/L; AMPK inhibitor) and wortmannin (0.5 µmol/L; PI3K inhibitor) only in combination with 200 µmol/L Gs-Rbl were administered in hypoxic cardiomyocytes, which were induced by 500 µmol/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-AMPKα (Thr172), AMPKα and Akt in cells were assayed.    

Results: Compared with simple hypoxia (0 µmol/L Gs-Rbl), Gs-Rb1 greater than 10 µmol/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 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