FEBS Letters · 2006 · 116 citations · 21 references
Life SciencesBiochemistryMolecular BiologyCell SignalingMolecular PharmacologySignal TransductionEndothelial ActivationEndothelial DysfunctionG Protein-coupled Receptor SignalingPhosphoinositide SignalingEndothelial Cell PhysiologyFluorescence Polarization ImagingFluorescence Polarization MicroscopyGlucocorticoid Receptor SignalingNitric OxideNitric Oxide ProductionNitric Oxide Synthase RegulationPi3k-akt Signaling Pathway
We here provide definitive evidence that ginsenoside-Rg1, the pharmacologically active component of ginseng, is a functional ligand of the glucocorticoid receptor (GR) as determined by fluorescence polarization assay. Rg1 increased the phosphorylation of GR, phosphatidylinositol-3 kinase (PI3K), Akt/PKB and endothelial nitric oxide synthase (eNOS) leading to increase nitric oxide (NO) production in human umbilical vein endothelial cell. Rg1-induced eNOS phosphorylation and NO production were significantly reduced by RU486, LY294,002, or SH-6. Also, knockdown of GR completely eliminated the Rg1-induced NO production. This study revealed that Rg1 can indeed serve as an agonist ligand for GR and the activated GR can induce rapid NO production from eNOS via the non-transcriptional PI3K/Akt pathway.
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Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Stefanie Dimmeler, Ingrid Fleming, Beate Fißlthaler et al. · Nature · 1999 · 3.6K citations