Involvement of IGF-I receptor and estrogen receptor pathways in the protective effects of ginsenoside Rg1 against Aβ25–35-induced toxicity in PC12 cells


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Abstract

HighlightsRg1 has neuroprotective effect against Aβ25–35-induced toxicity in PC12 cells.JB-1 or ICI182,780 blocks the protective effect of Rg1.Rg1 activates the MEK/ERK and estrogen receptor signaling pathway.Ginsenoside Rg1 is the main pharmacologically active compound of ginsenosides and has demonstrated pharmacological effects in the cardiovascular system, central nervous system and immune system. The involvement of insulin-like growth factor-I receptor (IGF-IR)-dependent pathway and estrogen receptor (ER)-dependent pathway in the biological effect of ginsenoside Rg1 have been demonstrated in our previous study. The present study tested the hypothesis that the protective effects of Rg1 against Aβ25–35-induced toxicity involved activation of the IGF-IR and ER signaling pathways in PC12 cells. Treatment with Aβ25–35 decreased the cell viability in a dose-dependent manner in PC12 cells. Rg1 pretreatment resulted in an enhancement of survival and the maximum protection occurred at the concentration of 1 μM. Co-treatment with IGF-IR antagonist JB-1 or ER antagonist ICI182,780 could completely block the protective effect of Rg1. The decreased Bcl-2 mRNA expression induced by Aβ25–35 could be restored by Rg1 pretreatment. Rg1 pretreatment could also restore the decreased mitochondrial membrane potential induced by Aβ25–35 and these effects could be completely blocked by JB-1 or ICI182,780. In addition, Rg1 treatment alone could significantly increase the phosphorylation level of MEK and ERK in a time-dependent manner and the functional transactivation of ERα in PC12 cells. The functional transactivation of ERα by Rg1 could be completely blocked by JB-1 or ICI182,780. Taken together, our results suggest that IGF-IR and ER signaling pathways might be involved in the protective effect of Rg1 against Aβ25–35-induced toxicity in PC12 cells.

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