title: Nitric oxide and its decomposed derivatives decrease the binding of extracellular-superoxide dismutase to the endothelial cell surface.
abstract: Extracellular-superoxide dismutase (EC-SOD) is bound to the vascular endothelial cell surface with an affinity for heparan sulfate proteoglycan. The binding of EC-SOD to the human umbilical vein endothelial cell (HUVEC) and bovine aortic endothelial cell surface proteoglycans was significantly decreased by the incubation with S-nitroso-N-acetyl-DL-penicillamine (SNAP) and +/- -N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexene-1-yl]-3-pyridine carboxamide (NOR4), potent nitric oxide (NO) donors. NO derived from lipopolysaccharide-stimulated J774 A-1 cells also decreased the binding of EC-SOD to HUVEC, and this decrease was blocked by N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor. SNAP and NOR4 also decreased the binding of EC-SOD to immobilized heparin. Furthermore, the decomposed derivatives of NO donors and sodium nitrite decreased the binding of EC-SOD. These observations suggest that excess NO produced in the inflammatory conditions decreases the binding of EC-SOD to the vascular endothelial cell surface, which results in a loss of the ability to protect the endothelial cell surface from oxidative stress.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Adachi
mesh_terms: D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology* / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000201:enzymology*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C102260:NOR 4; D020030:Nitric Oxide Donors; D009573:Nitrites; D011509:Proteoglycans; D011725:Pyridines; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D006493:Heparin; D013482:Superoxide Dismutase; D010396:Penicillamine