Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor.
Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic endothelial cells. However, the signaling pathways involved have not been well studied in human aortic endothelial cells. The present study was designed to examine whether purified ginsenoside Rb1, a major active component of ginseng could actually induce NO production and to clarify the signaling pathway in human aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid increase in NO production was abrogated by treatment with nitric oxide synthetase inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2 (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly, NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt and MEK/ERK pathways and androgen receptor are involved in the regulation of acute eNOS activation by Rb1 in human aortic endothelial cells.
Yu
Jing
J
Department of Integrated Traditional Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Eto
Masato
M
Akishita
Masahiro
M
Kaneko
Akiyo
A
Ouchi
Yasuyoshi
Y
Okabe
Tetsuro
T
D000595:Amino Acid Sequence; D059002:Androgen Receptor Antagonists; D000730:Androstadienes / Q000494:pharmacology; D001011:Aorta; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000077191:Wortmannin
D059002:Androgen Receptor Antagonists; D000730:Androstadienes; D005419:Flavonoids; D036145:Ginsenosides; D048289:Imidazolidines; D011944:Receptors, Androgen; D009569:Nitric Oxide; C021277:nilutamide; C442759:ginsenoside Rb1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin