title: Unusual peroxidase activity of polynitroxylated pegylated hemoglobin: Elimination of H(2)O(2) coupled with intramolecular oxidation of nitroxides.
abstract: Polynitroxylated hemoglobin (Hb(AcTPO)(12)) has been developed as a hemoglobin-based oxygen carrier. While Hb(AcTPO)(12) has been shown to exert beneficial effects in a number of models of oxidative injury, its peroxidase activity has not been characterized thus far. In the blood stream, Hb(AcTPO)(12) undergoes reduction by ascorbate to its hydroxylamine form Hb(AcTPOH)(12). Here we report that Hb(AcTPOH)(12) exhibits peroxidase activity where H(2)O(2) is utilized for intramolecular oxidation of its TPOH residues to TPO. This represents an unusual redox-catalytic mechanism whereby reduction of H(2)O(2) is achieved at the expense of reducing equivalents of ascorbate converted into those of Hb(AcTPOH)(12), a new propensity that cannot be directly associated with ascorbate.
authors.affiliation: Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Detcho A
authors.initials: DA
authors.lastname: Stoyanovsky
authors.forename: Alexandr
authors.initials: A
authors.lastname: Kapralov
authors.forename: Zhentai
authors.initials: Z
authors.lastname: Huang
authors.forename: Akihiro
authors.initials: A
authors.lastname: Maeda
authors.forename: Anatoly
authors.initials: A
authors.lastname: Osipov
authors.forename: Carleton J C
authors.initials: CJ
authors.lastname: Hsia
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Hulya
authors.initials: H
authors.lastname: Bayr
authors.forename: Valerian E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D003497:Cyclic N-Oxides / Q000097:blood / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000097:blood / Q000378:metabolism*
chemical_list: D003497:Cyclic N-Oxides; D006454:Hemoglobins; D009589:Nitrogen Oxides; D006861:Hydrogen Peroxide; D010544:Peroxidases