title: Involvement of IGF-I receptor and estrogen receptor pathways in the protective effects of ginsenoside Rg1 against Aβ₂₅₋₃₅-induced toxicity in PC12 cells.
abstract: 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 1μM. 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.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China. marychhk@yahoo.com
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Chen
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Quan-Gui
authors.initials: QG
authors.lastname: Gao
authors.forename: Man-Sau
authors.initials: MS
authors.lastname: Wong
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C074636:amyloid beta-protein (25-35); D011494:Protein Kinases; D017526:Receptor, IGF Type 1; C035054:ginsenoside Rg1