title: Nuclear translocation of extracellular superoxide dismutase.
abstract: Histochemical examination of mouse tissues showed nuclear staining of extracellular superoxide dismutase (EC-SOD), and the nuclear translocation of EC-SOD was also confirmed in cultured cells that had been transfected with its gene, as shown by immunohistochemistry and Western blot analysis. The EC-SOD which was secreted into the medium was incorporated into 3T3-L1 cells and a significant fraction of the material taken up was localized in the nucleus. Site-directed mutagenesis indicated that the heparin-binding domain of EC-SOD functions as the nuclear localization signal. These results suggest that the mechanism of the nuclear transport of EC-SOD involves a series of N-terminal signal peptide- and C-terminal heparin-binding domain-dependent processes of secretion, re-uptake and the subsequent nuclear translocation. The findings herein provide support for the view that the role of EC-SOD is to protect the genome DNA from damage by reactive oxygen species and/or the transcriptional regulation of redox-sensitive gene expression.
authors.affiliation: Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, 663-8501, Hyogo, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ookawara
authors.forename: Takako
authors.initials: T
authors.lastname: Kizaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Takayama
authors.forename: Nobuo
authors.initials: N
authors.lastname: Imazeki
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Li
authors.initials: L
authors.lastname: Li Ji
authors.forename: Takushi
authors.initials: T
authors.lastname: Tadakuma
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D019913:Nuclear Localization Signals; D010957:Plasmids; D021381:Protein Transport; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D006493:Heparin; D013482:Superoxide Dismutase