title: Ferric human neuroglobin scavenges superoxide to form oxy adduct.
abstract: Neuroglobin (Ngb) is the third member of the vertebrate globin family, and the structure was solved as a typical globin fold with a b-type heme. Although it has been proposed that Ngb could be involved in neuroprotection against oxidative stress, the protective mechanism has not been fully identified yet. In order to clarify functions under hypoxic condition, in this study, we focused on the scavenger activity of human Ngb (hNgb) against superoxide. The activity of hNgb for superoxide was evaluated to be 7.4 µM for IC50, the half maximal inhibitory concentration. The result indicates that hNgb can be an anti-oxidant, and the value was almost the same as that of ascorbic acid. In addition, we characterized oxidation states of a heme iron in superoxide-treated hNgb with spectroscopic measurements. Superoxide-treated hNgb in the ferric form was readily converted to the oxygenated ferrous form, and the result suggested that ferric hNgb could scavenge superoxide by change of an oxidation state in a heme iron. Moreover, mutational experiments were performed, and the each variant mutated at 46 and 55 positions suggested a disulfide bond between Cys46 and Cys55 could be essential to be sensors for oxidative stress with the direct binding of superoxide. As a consequence, we concluded that redox changes of the heme iron and the disulfide bond could regulate neuroprotective functions of hNgb, and it suggests that hNgb can afford protection against hypoxic and ischemic stress in the brain.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University.
authors.forename: Taku
authors.initials: T
authors.lastname: Yamashita
authors.forename: Leila
authors.initials: L
authors.lastname: Hafsi
authors.forename: Eri
authors.initials: E
authors.lastname: Masuda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tsujino
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Uno
mesh_terms: D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D005914:Globins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000078787:Neuroglobin; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D013481:Superoxides; D005914:Globins; D007501:Iron