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

被引：25

作者：

Chen, Wen-Fang ^{[1
,2
]}

Zhou, Li-Ping ^{[1
,2
]}

Chen, Lei ^{[1
,2
]}

Wu, Lin ^{[1
,2
]}

Gao, Quan-Gui ^{[1
,2
,3
]}

Wong, Man-Sau ^{[3
]}

机构：

[1] Qingdao Univ, Shandong Prov Key Lab Pathogenesis & Prevent Neur, Coll Med, Dept Physiol, Qingdao 266071, Peoples R China

[2] Qingdao Univ, State Key Disciplines Physiol, Coll Med, Qingdao 266071, Peoples R China

[3] Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Kowloon, Hong Kong, Peoples R China

来源：

NEUROCHEMISTRY INTERNATIONAL | 2013年 / 62卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Ginsenoside Rg1; beta-Amyloid peptide; Estrogen receptor; Insulin-like growth factor-I receptor; PC12; cells; GROWTH-FACTOR-I; ALZHEIMERS-DISEASE; PROTEIN; ESTRADIOL; KINASE; RAT; NEUROTOXICITY; THERAPEUTICS; ACTIVATION; APOPTOSIS;

D O I：

10.1016/j.neuint.2013.03.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 A beta(25-35)-induced toxicity involved activation of the IGF-IR and ER signaling pathways in PC12 cells. Treatment with A beta(25-35) 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 mu M. 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 A beta(25-35) could be restored by Rg1 pretreatment. Rg1 pretreatment could also restore the decreased mitochondrial membrane potential induced by A beta(25-35) 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 ER alpha in PC12 cells. The functional transactivation of ER alpha 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 A beta(25-35)-induced toxicity in PC12 cells. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1065 / 1071

页数：7

共 29 条

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