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A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension.

Publication ,  Journal Article
Liu, S; Premont, RT; Kontos, CD; Zhu, S; Rockey, DC
Published in: Nat Med
September 2005

Nitric oxide (NO) production by endothelial cell nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. We sought to understand the mechanism underlying defective eNOS function. Phosphorylation of the serine-threonine kinase Akt, which activates eNOS, was substantially reduced in sinusoidal endothelial cells from injured livers. Overexpression of Akt in vivo restored phosphorylation of Akt and production of NO and reduced portal pressure in portal hypertensive rats. We found that Akt physically interacts with G-protein-coupled receptor kinase-2 (GRK2), and that this interaction inhibits Akt activity. Furthermore, GRK2 expression increased in sinusoidal endothelial cells from portal hypertensive rats and knockdown of GRK2 restored Akt phosphorylation and NO production, and normalized portal pressure. Finally, after liver injury, GRK2-deficient mice developed less severe portal hypertension than control mice. Thus, an important mechanism underlying impaired activity of eNOS in injured sinusoidal endothelial cells is defective phosphorylation of Akt caused by overexpression of GRK2 after injury.

Duke Scholars

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

September 2005

Volume

11

Issue

9

Start / End Page

952 / 958

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Rats, Sprague-Dawley
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, S., Premont, R. T., Kontos, C. D., Zhu, S., & Rockey, D. C. (2005). A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Nat Med, 11(9), 952–958. https://doi.org/10.1038/nm1289
Liu, Songling, Richard T. Premont, Christopher D. Kontos, Shoukang Zhu, and Don C. Rockey. “A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension.Nat Med 11, no. 9 (September 2005): 952–58. https://doi.org/10.1038/nm1289.
Liu S, Premont RT, Kontos CD, Zhu S, Rockey DC. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Nat Med. 2005 Sep;11(9):952–8.
Liu, Songling, et al. “A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension.Nat Med, vol. 11, no. 9, Sept. 2005, pp. 952–58. Pubmed, doi:10.1038/nm1289.
Liu S, Premont RT, Kontos CD, Zhu S, Rockey DC. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Nat Med. 2005 Sep;11(9):952–958.

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

September 2005

Volume

11

Issue

9

Start / End Page

952 / 958

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Rats, Sprague-Dawley
  • Rats
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Nitric Oxide Synthase Type III
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Male