title: S-nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase.
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.
authors.affiliation: Johns Hopkins University School of Medicine, 720 Rutland Ave Ross 1150, Baltimore, MD 21205, USA.
authors.forename: Jessilyn
authors.initials: J
authors.lastname: Dunn
authors.forename: Sarah
authors.initials: S
authors.lastname: Gutbrod
authors.forename: Alanah
authors.initials: A
authors.lastname: Webb
authors.forename: Alina
authors.initials: A
authors.lastname: Pak
authors.forename: Simran K
authors.initials: SK
authors.lastname: Jandu
authors.forename: Anil
authors.initials: A
authors.lastname: Bhunia
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Santhanam
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D001119:Arginase / Q000378:metabolism*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D057075:Enzyme Assays; D006801:Humans; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015538:Nitrosation; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D010446:Peptide Fragments; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D001119:Arginase