title: Nitration of surfactant protein A (SP-A) tyrosine residues results in decreased mannose binding ability.
abstract: Nitric oxide (.NO) is a signal transducing free radical which can modify oxidant stress by limiting superoxide (O2.-)-mediated injury. However, the product of .NO reaction with O2.-, peroxynitrite (ONOO-), is a potent oxidizing and nitrating agent. Exposure of a mixture containing phosphatidylcholine liposomes and surfactant apoprotein A (SP-A; 10% by weight) to increasing concentrations of .NO, generated by spermine NONOate, and constant O2.- levels, produced by the action of xanthine oxidase on lumazine, suppressed O2.(-)-induced lipid peroxidation in the presence of Fe3(+)- EDTA. On the other hand, an increase in the .NO/O2.- value resulted in nitration of SP-A tyrosine residues, located in the carbohydrate recognition domain (CRD), and decreased the ability of SP-A to aggregate lipids and bind mannose, two functions that require an intact CRD. SP-A was also nitrated to a large extent following exposure to 3-morpholinosydnonimine (SIN-1) or tetranitromethane at pH 8. In each case, increased nitrotyrosine content correlated in a monotonic fashion with inhibition of lipid aggregation and mannose binding, correlated with the extent of functional inhibition. Superoxide dismutase (2400 U/ml) and urate (100 microM; nonspecific scavenger of both ONOO- and hydroxyl radical), but not mannitol (50 mM; hydroxyl radical scavenger), prevented the SIN-1-induced injury to SP-A. In contrast, spermine NON-Oate or xanthine oxidase plus lumazine alone neither inhibited SP-A function nor nitrated the protein. These results indicate that at high concentrations, .NO inhibit O2.-induced lipid peroxidation. However, ONOO., formed by the reaction of .NO and O2.-, nitrates SP-A leading to decreased ability to aggregate lipids and bind mannose.
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham 35233-6810, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.forename: I Y
authors.initials: IY
authors.lastname: Haddad
authors.forename: S
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000818:Animals; D001665:Binding Sites; D016166:Free Radical Scavengers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation; D008081:Liposomes; D008358:Mannose / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011510:Proteolipids / Q000737:chemistry* / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013774:Tetranitromethane / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry
chemical_list: D016166:Free Radical Scavengers; D008081:Liposomes; D009566:Nitrates; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D013481:Superoxides; D009569:Nitric Oxide; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; D013774:Tetranitromethane; D008358:Mannose