Ginsenoside Rg1 activated CaMKIIalpha mediated extracellular signal-regulated kinase/mitogen activated protein kinase signaling pathway.
OBJECTIVE
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.
Hu
Jin-feng
JF
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Xue
Wei
W
Ning
Na
N
Yuan
Yu-he
YH
Zhang
Jun-tian
JT
Chen
Nai-hong
NH
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D036145:Ginsenosides; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C035054:ginsenoside Rg1