title: AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress.
abstract: OBJECTIVE
  The regulation of AMP-activated protein kinase (AMPK) is implicated in vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS). In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a mouse model with a high level of voluntary running (High-Runner).
  
  
  RESULTS
  By using flow channels with cultured ECs, AMPK Thr172 phosphorylation was increased with changes of flow rate or pulsatility. The activity of LKB1, the upstream kinase of AMPK, and the phosphorylation of eNOS at Ser1179 were concomitant with AMPK activation responding to changes in flow rate or pulsatility. The blockage of AMPK by a dominant-negative mutant of AMPK inhibited shear stress-induced eNOS Ser1179 phosphorylation and NO production. Furthermore, aortic AMPK activity and level of eNOS phosphorylation were significantly elevated in the aortas of High-Runner mice.
  
  
  CONCLUSIONS
  Our results suggest that shear stress activates AMPK in ECs, which contributes to elevated eNOS activity and subsequent NO production. Hence, AMPK, in addition to serving as an energy sensor, also plays an important role in regulating vascular tone.
authors.affiliation: Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
authors.forename: Erik M
authors.initials: EM
authors.lastname: Kolb
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.forename: Frances M
authors.initials: FM
authors.lastname: Sladek
authors.forename: Ghassan S
authors.initials: GS
authors.lastname: Kassab
authors.forename: Theodore
authors.initials: T
authors.lastname: Garland
authors.forename: John Y-J
authors.initials: JY
authors.lastname: Shyy
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D001011:Aorta / Q000201:enzymology; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011673:Pulsatile Flow; D013314:Stress, Mechanical
chemical_list: D009097:Multienzyme Complexes; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases