Anti-hypoxic effect of ginsenoside Rb1 on neonatal rat cardiomyocytes is mediated through the specific activation of glucose transporter-4 ex vivo

作者：Kong, Hong-liang^*; Wang, Jian-ping; Li, Zhan-quan; Zhao, Shu-mei; Dong, Jing; Zhang, Wei-wei

来源：Acta Pharmacologica Sinica, 2009, 30(4): 396-403.

DOI：10.1038/aps.2009.2

• neonatal rat cardiomyocytes
• hypoxia
• apoptosis
• ginsenosides-Rb1
• glucose transporter-4

Aim: The aim of this study was to investigate whether Gs-Rb1 relieves the CoCl2-induced apoptosis of hypoxic neonatal rat cardiomyocytes and in which the role of glucose transporter-4 (GLUT-4).
Methods: Gs-Rb1 (0, 10, 50, 100, 200, 400, and 500 mu mol/L), adenine 9-beta-D-arabinofuranoside (ara A, 500 mu mol/L; AMPK inhibitor) and wortmannin (0.5 mu mol/L; PI3K inhibitor) only in combination with 200 mu mol/L Gs-Rb1 were administered in hypoxic cardiomyocytes, which were induced by 500 mu mol/L CoCl2 for 12 h. Then, the apoptotic rate (AR), 2-[H-3]-deoxy-D-glucose (2-[H-3]-DG) uptake, and the expression of GLUT-4 ( including in plasma membrane, PM), phospho-AMPK alpha (Thr172), AMPK alpha and Akt in cells were assayed.
Results: Compared with simple hypoxia (0 mu mol/L Gs-Rb1), Gs-Rb1 greater than 10 mu mol/L significantly decreased the apoptotic rate (P<0.01) and significantly increased 2-[H-3]-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 adose-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.

• 出版日期2009-4
• 单位辽宁省人民医院; 沈阳师范大学