Activating glucocorticoid receptor-ERK signaling pathway contributes to ginsenoside Rg1 protection against β-amyloid peptide-induced human endothelial cells apoptosis.
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.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-N
Rg1 Ginsenoside Rg1 Rg1 Rg1 Rg1 nitrogen RU486 U0126 estrogen ICI 82,780 Rg1 ginsenoside Rg1 Aβ25-35 GR ERK β-amyloid Aβ Aβ Aβ25-35 HIF-1α glucocorticoid receptor GR p-ERK estrogen receptor α Aβ25-35 GR ERK HIF-1α β-amyloid peptide glucocorticoid receptor ERK