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The role of reactive oxygen species in adipocytes and obesity: with special reference to extracellular SOD

Research Project

Project/Area Number 13470084
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKyorin University, School of Medicine

Principal Investigator

OHNO Hideki  Kyorin University, School of Medicine, Department of Molecular Predictive Medicine and Sport Science, Professor, 医学部, 教授 (00133819)

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)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
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)
Keywordsextracellular 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
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.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Kizaki, T. et al.: "Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages"Proc. Natl. Acad. Sci. USA. 99. 9392-9397 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ookawara, T. et al.: "Nuclear translocation of extracellular superoxide dismutase"Biochem. Biophys. Res. Commun.. 296. 54-61 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Radak, Z. et al.: "Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon"Exp. Gerontol.. 37. 1423-1430 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ookawara, T. et al.: "Effects of endurance training on three superoxide dismutase isoenzyme in human plasma"Free Radic. Res.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimoto, K. et al.: "Gliclazide protects pancreatic beta-cells from damages by hydrogen peroxide"Biochem. Biophys. Res. Commun.. 303. 112-119 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, H. et al.: "Extracellular superoxide dismutase and lifestyle related diseases"Curr. Top. Pharmacol.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 大野 秀樹他編: "Q&A 運動と遺伝"大修館書店. 259 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno,H., et al.: "Physical exercise and uncoupling protein family (Review)"Adv. Exerc. Sports Physiol.. 7. 1-15 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Radak,Z., et al.: "Telomerase activity is not alterd by regular strenuous exercise in skeletal muscle or by sarcoma in liver of rats"Redox Rep.. 6. 99-103 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Radak,Z., et al.: "Adaptation to exercise-induced oxidative stress: from muscle to brain (Review)"Exerc. Immunol. Rev.. 7. 90-107 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sitoh, D., et al.: "Characteristics of plasma extracellular SOD in burned patients"Burns. 27. 577-581 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kizaki,T., et al.: "Activation and apoptosis of murine peritoneal macropharges by acute cold stress"Biochem. Biophys. Res. Commun.. 281. 700-706 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hollander,J., et al.: "Superoxide dismutase gene expression is activated by a single bout of exercise in rat skeletal muscle"Pflugers Arch.. 442. 426-434 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Radak,Z., et al.: "Single bout of exercise eliminates the immobilization-induced oxidative stress in rat brain"Neurochem. Int.. 39. 33-38 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kizaki,T., et al.: "Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase by AP-1 in macrophage cell line"Biochem. Biophys. Res. Commun.. 289. 1031-1038 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kizaki,T., et al.: "Stress- and aging -associated modulation of macrophage functions (Review)"Environ. Health Prev. Med.. 6. 218-228 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito,Y., et al.: "Exercise training increases membrane bound form of tumor necrosis factor- α receptors with decreases in the secretion of soluble forms of receptors in the rat adipocytes"Life Sci.. 70. 601-609 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kizaki,T., et al.: "Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide- stimulated macrophages"Proc. Natl. Acad. Sci. USA. 99. 9392-9397 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nomura,S., et al.: "Possible mechanisms by which adipocyte lipolysis is enhanced in exercise-trained rats"Biochem. Biophys. Res. Commun.. 295. 236-242 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ookawara,T., et al.: "Nuclear translocation of extracellular superoxide dismutase"Biochem. Biophys. Res. Commun.. 296. 54-* (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Radak,Z., et al.: "Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon"Exp. Gerontol.. 37. 1423-1430 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimoto,K., et al.: "Gliclazide protects pancreatic beta- cells from damage by hydrogen peroxide"Biochem. Biophys. Res. Commun.. 303. 112-119 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ookawa,T., et al.: "Effects of oxidative stress on the nuclear translocation of extracellular superoxide dismutase"Biochem. Biophys. Res. Commun.. 303. 914-919 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Gotoh,Y., et al.: "Dissociation between gene expression and protein contents of tissue superoxide dismutase in a rat model of lethal burns"Burns. 29. 115-122 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno,H., et al.: "Extracellular superoxide dismutase and lifestyle related diseases (Review)"Curr. Top. Pharmacol. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kizaki, T. et al.: "Uncoupling protein 2 plays an important role in nitric oxide production of lipopolysaccharide-stimulated macrophages"Proc.Natl.Acad.Sci.USA. 99. 9392-9397 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ookawara, T. et al.: "Nuclear translocation of extracellular superoxide dismutase"Biochem.Biophys.Res.Commun. 296. 54-61 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Radak, Z. et al.: "Effect of aging and late onset dietary restriction on antioxidant enzymes and proteasome activities, and protein carbonylation of rat skeletal muscle and tendon"Exp.Gerontol.. 37. 1423-1430 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ookawara, T. et al.: "Effects of endurance training on three superoxide dismutase isoenzyme in human plasma"Free Radic.Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimoto, K. et al.: "Gliclazide protects pancreatic beta-cells from damages by hydrogen peroxide"Biochem.Biophys.Res.Commun.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohno, H. et al.: "Extracellular superoxide dismutase and lifestyle related diseases"Curr.Top.Pharmacol. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大野秀樹・他編: "Q&A 運動と遺伝"大修館書店. 259 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito, Y.: "Exercise training increases membrane bound form of tumor necrosis factor-a receptors with decreases in the secretion of soluble forms of receptors in rat adipocytes"Life Sci.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kizaki, T.: "Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase by AP 1 in macrophage cell line J774A.1"Biochem. Biophys. Res. Commun.. 289・5. 1031-1038 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kizaki, T.: "Activation and apoptosis of murine peritoneal macrophages by acute cold stress"Biochem. Biophys. Res. Commun.. 283・3. 700-706 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Radak, Z: "Adaptation to exercise-induced oxidative stress : from muscle to brain"Exerc.Immunol.Rev.. 7. 90-107 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Radak, Z: "Telomerase activity is not altered by regular strenuous exercise in skeletal muscle or by sarcoma in liver of rats"Redox Rep.. 6・2. 99-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Redak, Z: "Single bout of exercise eliminates the immobilization -induced oxidative stress in rat brain"Neurochem.Int.. 39・1. 33-38 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohno, H.: "Physical exercise and uncoupling protein family"Adv.Exerc.Sports Physiol.. 7・1. 1-15 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saitoh, D.: "Characteristics of plasma extracellular SOD in burned patients"Burns. 27・6. 577-581 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hollander, J.: "Superoxide dismutase gene expression is activated by a single bout of exercise in rat skeletal muscle"Pflugers Arch.. 442・3. 426-434 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Harada, M.: "Mercury pollution in the Tapajos River basin, Amazon : mercury level of head hair and health effects"Environ.Int.. 27・4. 285-290 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kizaki, T.: "Stress-and aging associated modulation of macrophage functions"Environ.Health Prev.Med.. 6・4. 218-228 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大野 秀樹: "Q&A運動と遺伝"大修館書店. 259 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大野 秀樹: "運動生理・生化学辞典"大修館書店. 525 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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