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Ginsenoside Rg1 activated CaMKIIalpha mediated extracellular signal-regulated kinase/mitogen activated protein kinase
Jin-feng Hu1, Wei Xue, Na Ning
1Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Aim:
We carried out this study to investigate the effect of ginsenoside Rg1 on the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/ MAPK) pathway for understanding its effect on synaptic platicity.
Methods:
Western blotting and immunostaining were used to examine the phosphorylation of ERK1/2, CaMKIIalpha and cAMP response element binding protein (CREB) in PC12 cells and synaptosomes. The confocal microscopy and fluorescent indicator Fluo-3 was applied to observe the intracellular calcium ion flux.
Results:
The phosphorylation of ERK1/2 in PC12 cells and synaptosomes incubated with Rg1 was increased and reached maximum at 4 min. Rg1 also promoted the transient enhancement of upstream calcium ion and activated CaMKIIalpha, which reached maximum at 2 min. CREB, the downstream protein, was phosphorylated within 8 min in PC12 cells after being incubated with Rg1. Moreover, KN93 partially inhibited the activation of ERK1/2, and PD98059 also partially blocked the phosphorylation of CREB.
Conclusions:
Rg1 activated ERK/MAPK pathway by CaMKIIalpha, and the activation of CREB was not only dependent on ERK induced by Rg1, which may provide an explanation for the effect of Rg1 on long-term potentiation.
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