Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

Title
Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase
Author(s)
황용필[황용필]김형균[김형균]트란 티 히엔[트란 티 히엔]정명호[정명호]정태천정혜광[정혜광]
Keywords
KAPPA-B PATHWAY; TRANSCRIPTIONAL ACTIVITY; VASCULAR-DISEASE; HEME OXYGENASE-1; GENE-EXPRESSION; UP-REGULATION; CELLS; DYSFUNCTION; AKT; NO
Issue Date
201111
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
TOXICOLOGY AND APPLIED PHARMACOLOGY, v.257, no.1, pp.48 - 58
Abstract
The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-alpha-stimulated monocytes to endothelial cells and suppressed the INF-alpha induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the INF-alpha-induced nuclear factor-kappa B activation, which was attenuated by pretreatment with N-G-nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. (C) 2011 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/24266http://dx.doi.org/10.1016/j.taap.2011.08.017
ISSN
0041-008X
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약학대학 > 약학부 > Articles
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