Reactivity studies of the Fe(III) and Fe(II)NO forms of human neuroglobin reveal a potential role against oxidative stress.
Neuroglobin, recently discovered in the brain and in the retina of vertebrates, belongs to the class of hexacoordinate globins, in which the distal histidine coordinates the iron center in both the Fe(II) and Fe(III) forms. As for most other hexacoordinate globins, the physiological function of neuroglobin is still unclear, but seems to be related to neuronal survival following acute hypoxia. In this study, we have addressed the question whether human neuroglobin could act as a scavenger of toxic species, such as nitrogen monoxide, peroxynitrite, and hydrogen peroxide, which are generated at high levels in the brain during hypoxia; we have also investigated the kinetics of the reactions of its Fe(III) (metNGB) and Fe(II)NO forms with several reagents. Binding of cyanide or NO* to metNGB follows bi-exponential kinetics, showing the existence of two different protein conformations. In the presence of excess NO*, metNGB is converted into NGBFe(II)NO by reductive nitrosylation, in analogy to the reactions of NO* with metmyoglobin and methemoglobin. The Fe(II)NO form of neuroglobin is oxidized to metNGB by peroxynitrite and dioxygen, two reactions that also take place in hemoglobin, albeit at lower rates. In contrast to myoglobin and hemoglobin, metNGB unexpectedly does not generate the cytotoxic ferryl form of the protein upon addition of either peroxynitrite or hydrogen peroxide. Taken together, our data indicate that human neuroglobin may be an efficient scavenger of reactive oxidizing species and thus may play a role in the cellular defense against oxidative stress.
Herold
Susanna
S
Laboratorium für Anorganische Chemie, Eidgenössische Technische Hochschule Hönggerberg, CH-8093 Zürich, Switzerland. herold@inorg.chem.ethz.ch
Fago
Angela
A
Weber
Roy E
RE
Dewilde
Sylvia
S
Moens
Luc
L
D005290:Ferric Compounds / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D005914:Globins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D000078787:Neuroglobin; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*
D005290:Ferric Compounds; D005296:Ferrous Compounds; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D009569:Nitric Oxide; D005914:Globins