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Neurogranin regulates eNOS function and endothelial activation.

Vino T Cheriyan1, Mabruka Alfaidi2, Ashton N Jorgensen1

  • 1Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.

Redox Biology
|March 17, 2020
PubMed
Summary
This summary is machine-generated.

Neurogranin (Ng) regulates endothelial nitric oxide synthase (eNOS) activity and NO production. This protein is crucial for maintaining vascular function and preventing endothelial dysfunction, impacting cardiovascular disease.

Keywords:
Endothelial dysfunctionFlow-mediated dilationNeurograninNitric oxideOxidative stressShear stress

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Area of Science:

  • Vascular Biology
  • Endothelial Cell Signaling
  • Cardiovascular Physiology

Background:

  • Endothelial nitric oxide (NO) is vital for vascular function and remodeling.
  • Endothelial nitric oxide synthase (eNOS) produces NO via calcium-dependent and independent pathways.

Purpose of the Study:

  • To investigate the role of neurogranin (Ng), a brain Ca2+-calmodulin signaling regulator, in endothelial cells (EC) and eNOS regulation.
  • To determine Ng's impact on vascular function and cardiovascular disease pathophysiology.

Main Methods:

  • Ng knockdown in human aortic endothelial cells (HAEC) using siRNA.
  • Ng knockout (Ng-/-) in mice.
  • Assessment of eNOS activity, NO production, phosphorylation, and expression under various conditions, including shear stress.
  • Flow-mediated dilation experiments in mice.

Main Results:

  • Ng depletion decreased eNOS activity and NO production in HAEC and mice.
  • Shear stress reduced Ng expression, further decreasing eNOS expression and S1177 phosphorylation.
  • Ng deficiency impaired AKT-dependent eNOS phosphorylation and NF-κB-mediated eNOS expression, promoting endothelial activation.
  • Ng deletion reduced eNOS activity and caused endothelial dysfunction in mice.

Conclusions:

  • Neurogranin (Ng) is essential for Ca2+-calmodulin-dependent eNOS regulation in endothelial cells.
  • Ng plays a critical role in maintaining vascular function and contributes to vascular remodeling, relevant to cardiovascular disease.