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 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 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.
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Acknowledgements
We thank Prof Hai-peng ZHANG (Department of Pathophysiology, China Medical University) for providing reagents.
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Kong, Hl., Wang, Jp., Li, Zq. et al. Anti-hypoxic effect of ginsenoside Rbl on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo. Acta Pharmacol Sin 30, 396–403 (2009). https://doi.org/10.1038/aps.2009.2
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DOI: https://doi.org/10.1038/aps.2009.2
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