S-nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase

Mol Cell Biochem. 2011 Sep;355(1-2):83-9. doi: 10.1007/s11010-011-0841-2. Epub 2011 May 1.

Abstract

Arginase constrains endothelial nitric oxide synthase activity by competing for the common substrate, L -Arginine. We have recently shown that inducible nitric oxide synthase (NOS2) S-nitrosates and activates arginase 1 (Arg1) leading to age-associated vascular dysfunction. Here, we demonstrate that a direct interaction of Arg1 with NOS2 is necessary for its S-nitrosation. The specific domain of NOS2 that mediates this interaction is identified. Disruption of this interaction in human aortic endothelial cells prevents Arg1 S-nitrosation and activation. Thus, disruption of NOS2-Arg1 interaction may represent a therapeutic strategy to attenuate age related vascular endothelial dysfunction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / pathology
  • Animals
  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / enzymology
  • Arginase / metabolism*
  • Cell Line
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Enzyme Assays
  • Humans
  • Immunoprecipitation
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitrates / metabolism*
  • Nitric Oxide Synthase Type II / chemistry
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitrosation
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Lipopolysaccharides
  • Nitrates
  • Peptide Fragments
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Arginase