RT Journal Article
SR Electronic
T1 Nectandrin B Activates Endothelial Nitric-Oxide Synthase Phosphorylation in Endothelial Cells: Role of the AMP-Activated Protein Kinase/Estrogen Receptor α/Phosphatidylinositol 3-kinase/Akt Pathway
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1166
OP 1178
DO 10.1124/mol.111.073502
VO 80
IS 6
A1 Tran Thi Hien
A1 Won Keun Oh
A1 Phi Hung Nguyen
A1 Seok Jeong Oh
A1 Moo Yeol Lee
A1 Keon Wook Kang
YR 2011
UL http://molpharm.aspetjournals.org/content/80/6/1166.abstract
AB We revealed previously that nectandrin B isolated from Myristica fragrans (nutmeg, Myristicaceae) functions as a potent AMP-activated protein kinase (AMPK) activator and showed its antiobesity effect. In this study, we investigated whether nectandrin B affects phosphorylation of endothelial nitric-oxide synthase (eNOS) in human endothelial cells. Nectandrin B increased the phosphorylation of eNOS and nitric oxide (NO) production in a concentration-dependent manner and maximal effect was found at 10 μg/ml. Nectandrin B activates AMPK, presumably via Ca2+/calmodulin kinase II activation and nectandrin B-stimulated eNOS phosphorylation was reversed by AMPK inhibition. Both the enzyme activity of phosphatidylinositol 3-kinase (PI3K) and the estrogen receptor (ER)-dependent reporter gene transcription were enhanced by nectandrin B. ERα inhibition by specific antagonist or small interfering siRNA (siRNA) suppressed nectandrin B-mediated eNOS phosphorylation. Moreover, AMPK inhibition significantly reversed the activation of ER-dependent transcription and PI3K activation in response to nectandrin B. Nectandrin B evoked endothelium-dependent relaxation in rat aortic rings, and this was blocked by inhibition of AMPK, ER, or PI3K. These results suggest that potent AMPK activator nectandrin B enhances NO production via eNOS phosphorylation in endothelial cells and ERα-dependent PI3K activity is required.