title: Piceatannol, a natural hydroxylated analog of resveratrol, promotes nitric oxide release through phosphorylation of endothelial nitric oxide synthase in human endothelial cells.
abstract: OBJECTIVE
  Endothelial dysfunction associated with many cardiovascular diseases is largely due to reduced nitric oxide (NO) derived from endothelial NO synthase (eNOS). Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene; Pic) is reported to have cardiovascular therapeutic effects. However, the cellular and molecular mechanisms underlying the cardioprotective effects of Pic are still unclear. Here, we investigated whether Pic could influence endothelial NO release in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  In HUVECs exposed to Pic, NO production and phosphorylation of eNOS and protein kinase B (Akt) were determined by using a commercially available NO assay kit and Western blot analysis, respectively.
  
  
  RESULTS
  Pic stimulated dose- and time-dependent NO production via eNOS phosphorylation. Pic also stimulated dose-dependent phosphorylation of Akt. Interestingly, NO production and eNOS phosphorylation in response to Pic were significantly abolished by the phosphoinositide 3-kinase (PI3K)/Akt inhibitor LY294002.
  
  
  CONCLUSIONS
  Pic is capable of inducing eNOS phosphorylation and the subsequent NO release, presumably, by activating PI3K/Akt pathway. The potential efficacy of Pic, a natural hydroxylated analog and a metabolite of resveratrol, may aid in the prevention of cardiovascular diseases characterized by endothelial dysfunction.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan, South Korea. hopae@wku.ac.kr.
authors.forename: Y
authors.initials: Y
authors.lastname: Son
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: Y-K
authors.initials: YK
authors.lastname: Cheong
authors.forename: H C
authors.initials: HC
authors.lastname: Jung
authors.forename: S-O
authors.initials: SO
authors.lastname: Jeong
authors.forename: S H
authors.initials: SH
authors.lastname: Park
authors.forename: H-O
authors.initials: HO
authors.lastname: Pae
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D013267:Stilbenes; D009569:Nitric Oxide; C041525:3,3',4,5'-tetrahydroxystilbene; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases