title: Activating glucocorticoid receptor-ERK signaling pathway contributes to ginsenoside Rg1 protection against β-amyloid peptide-induced human endothelial cells apoptosis.
abstract: The deposition of β-amyloid (Aβ) in neurons and vascular cells of the brain has been characterized in Alzheimer's disease. Ginsenoside Rg1 (Rg1) is an active components in Panax ginseng, a famous traditional Chinese medicines recorded in Compendium of Materia Medica. Present study attempted to evaluate the potential mechanisms of Aβ-mediated insult and the protective effects of Rg1 on human endothelial cells. Rg1 attenuated the Aβ25-35-associated mitochondrial apoptotic events, accompanied by inhibiting HIF-1α expression followed by intracellular reactive nitrogen species generation, and protein nitrotyrosination. These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than estrogen receptor α antagonist ICI 82,780. Taken together, our results suggested that Rg1 protected against Aβ25-35-induced apoptosis at least in part by two complementary GR-dependent ERK phosphorylation pathways: (1) down-regulating HIF-1α initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades. These data provided a novel insight to the mechanisms of Rg1protective effects on Aβ25-35-induced endothelial cells apoptosis, suggesting that GR-ERK signaling pathway might play an important role in it.
authors.affiliation: Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jieping
authors.initials: J
authors.lastname: Yan
authors.forename: Qibing
authors.initials: Q
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Dou
authors.forename: Yini
authors.initials: Y
authors.lastname: Hsieh
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Rongrong
authors.initials: R
authors.lastname: Tao
authors.forename: Danyan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yijia
authors.initials: Y
authors.lastname: Lou
mesh_terms: D016229:Amyloid beta-Peptides; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002070:Butadienes; D036145:Ginsenosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009570:Nitriles; D010446:Peptide Fragments; D020011:Protective Agents; D017382:Reactive Oxygen Species; D011965:Receptors, Glucocorticoid; C113580:U 0126; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D015735:Mifepristone; C002744:3-nitrotyrosine; D014443:Tyrosine; C035054:ginsenoside Rg1