Nuclear translocation of extracellular superoxide dismutase.
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.
Ookawara
Tomomi
T
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, 663-8501, Hyogo, Japan.
Kizaki
Takako
T
Takayama
Eiji
E
Imazeki
Nobuo
N
Matsubara
Osamu
O
Ikeda
Yoshitaka
Y
Suzuki
Keiichiro
K
Li Ji
Li
L
Tadakuma
Takushi
T
Taniguchi
Naoyuki
N
Ohno
Hideki
H
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*
D019913:Nuclear Localization Signals; D006493:Heparin; D013482:Superoxide Dismutase