| Project/Area Number |
13470084
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Kyorin University, School of Medicine |
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Principal Investigator |
OHNO Hideki Kyorin University, School of Medicine, Department of Molecular Predictive Medicine and Sport Science, Professor, 医学部, 教授 (00133819)
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| Co-Investigator(Kenkyū-buntansha) |
HITOMI Yoshiaki Kyorin University, School of Medicine, Department of Molecular Predictive Medicine and Sport Science, Assistant, 医学部, 助手 (70231545)
SUZUKI Kenji Kyorin University, School of Medicine, Department of Molecular Predictive Medicine and Sport Science, Assistant Professor, 医学部, 講師 (10187726)
KIZAKI Takako Kyorin University, School of Medicine, Department of Molecular Predictive Medicine and Sport Science, Associate Professor, 医学部, 助教授 (00322446)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2001: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | extracellular SOD / obesity / adipocyte / reactive oxygen species / uncoupling protein / heparin affinity / nuclear translocation / nitric oxide / ヘパリン親和性ドメイン / 白色脂肪細胞 / 褐色脂肪細胞 / 糖尿病 / 運動トレーニング |
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| Research Abstract |
Extracellular superoxide dismutase (EC-SOD) is a copper- and zinc-containing secretary glycoprotein, located in extracellular fluids including plasma and the extracellular matrix of tissues. The primary structure of EC-SOD indicates that the enzyme consists of an N-terminal hydrophobic signal peptide for secretion, a Cu, Zn-SOD-like domain in the middle portion, and a heparin-binding region, which contains clusters of positively charged amino acids in the C-terminal portion, as well as one potential site for N-linked gycosylation. Histochemical examination of mouse tissues showed nuclear staining of EC-SOD, and the nuclear translocation of EC-SOD was also confirmed in cultured cells. The EC-SOD which wa secreted into the medium was incorporated into 3T3-L1 preadipocytes and a significant fraction of the material taken up was localized in the mucleus. Site-directed mutagenesis indicated that the heparin-binding domain of EC-SOD functions as the nuclear localization signal. Moreover, EC-SOD was incorporated from conditioned medium of stable EC-SOD expressing CHO-EK cells into 3T3-L1 cells within 15 min. The uptake was clearly inhibited by the addition of heparin at a concentration of 0.4 μg/ml. Nuclear translocation of the incorporated EC-SOD was markedly enhanced by H_2O_2 treatment following incubation with the CHO-EK medium. The results obtained here suggest that the upregulation of the nuclear translocation of EC-SOD by oxidative stress might play a role in the mechanism by which the nucleus is protected against oxidative damage of genomic DNA, possibly leading to a low incidence of lifestyle related diseases such as cancer.
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