title: Structural and functional analysis of native peroxiredoxin 2 in human red blood cells.
abstract: Peroxiredoxin 2, a typical 2-Cys peroxiredoxin, is the third most abundant protein in erythrocytes. It is understood that the physiologically functional state of peroxiredoxin 2 is the monomer, and that its role in scavenging low levels of H(2)O(2) results in the formation of disulfide-linked dimers, which are reversibly reduced to monomers by the thioredoxin-thioredoxin reductase system. Additionally, peroxiredoxins are highly susceptible to sulfinic acid formation through reactions with various peroxides. This overoxidized form, which is thought to convert peroxiredoxins into molecular chaperones and to be accompanied by a transition to polymeric forms, can be reversed by sulfiredoxins. However, physiological conformational changes and the antioxidant role of erythrocyte peroxiredoxin 2 are still unclear because there is low sulfiredoxin and thioredoxin-thioredoxin reductase activity in erythrocytes. In this study, we examined the structural and redox states of peroxiredoxin 2 in fresh hemolysates and estimated the activities of native and overoxidized peroxiredoxin 2 purified from red blood cells to clear the physiological roles of peroxiredoxin 2 in erythrocyte. Our findings demonstrate that native peroxiredoxin 2 exists as high molecular weight (>160 kDa) oligomers and that decamers or higher order molecular weight oligomers (260-460 kDa) have peroxidase activity. We further showed that peroxiredoxin 2 oligomers, which were predominantly composed of monomers in the reduced form, exert a chaperone activity equal to that of overoxidized peroxiredoxin 2 polymers. These results provide the novel insight that redox-active peroxiredoxin 2 functions in human red blood cells as high molecular weight oligomers that possess peroxidase and chaperone activities.
authors.affiliation: Department of Hygienic Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. yo@my-pharm.ac.jp
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Takuya
authors.initials: T
authors.lastname: Ohminato
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000328:Adult; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D018832:Molecular Chaperones / Q000097:blood*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000097:blood; D054464:Peroxiredoxins / Q000097:blood*; D013329:Structure-Activity Relationship; D055815:Young Adult
chemical_list: D018832:Molecular Chaperones; D010544:Peroxidases; D054464:Peroxiredoxins