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Monitoring system of oxidative stress and therapeutic approach to oxidative stress-associated disorders by redox-regulating drugs

Research Project

Project/Area Number 09357022
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

YODOI Junji  Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (80108993)

Co-Investigator(Kenkyū-buntansha) WADA Hiromi  Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (90167205)
MATSUMORI Akira  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (70135573)
KUMAGAI Shunichi  Kobe University, School of Medicine, Professor, 医学部, 教授 (00153346)
HIROTA Kiichi  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00283606)
INAMOTO Takashi  Kyoto University, College of Medical Technology, Professor, 医療技術短期大学部, 教授 (10135577)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥28,000,000 (Direct Cost: ¥28,000,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1998: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1997: ¥15,400,000 (Direct Cost: ¥15,400,000)
Keywordsthioredoxin / redox / oxidative stress / ELISA / transgenic mouse / ADF
Research Abstract

Human thioredoxin (TRX) is induced by a variety of oxidative stress. It has multiple functions such as anti-oxidant activity, regulation of transcription factors, and cytokine or chemokine-like activities. In this study, we measured serum/plasma TRX levels using ELISA to evaluate their relation to oxidative stress.
1. Plasma levels of TRX were elevated in HIV-infected patients and correlated with decreases of intracellular glutathione levels in lymphocytes and changes of lymphocyte surface markers. The prognosis of patients with elevated plasma TRX was poor.
2. Serum TRX levels in HCV-infected patients were significantly higher than in normal individuals. Serum TRX levels correlated with the disease progression of hepatitis and serum ferritin levels. Patients with higher serum TRX levels exhibited resistance to IFN therapy.
3. Serum levels of TRX were elvated in patients with autoimmune diseases, such as SLE, rheumatoid arthritis (RA) and Sjogren's syndrome. TRX levels in knee synovial fl … More uid of patients with RA correlated with serum CRP levels, and were higher than that in patients with other arthritis such as arthritis deformans.
4. During open heart surgery with cardiopulmonary bypass, plasma TRX levels were elevated after reperfusion of the postcardioplegic heart.
5. TRX expression in rat hearts increased 24 hours after transient coronary artery occlusion. Administration of recombinant human TRX decreased the activation of NF-κB and ischemia/reperfusion injury.
6. After middle cerebral artery occlusion, TRX expression in rats decreased in the ischemic core regions, but increased in the perifocal ischemic regions. The infarct areas and volume were significantly smaller in TRX trangenic mice than in control mice.
Thus, our results suggest that TRX levels reflect oxidative stress and the measurement of TRX would give us insights into pathogenesis of oxidative stress-associated disorders. Moreover, administration of TRX may be useful for preventing oxidative stress and cure for its associated diseases. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Nakamura,H.他: "Pedux regulation of cellular activaton"Annu. Rev. Immunol.. 15. 351-369 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi,Y.他: "Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat"Takagi, Y.他. 18. 206-214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi,Y.他: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage"Takagi, Y.他. 96. 4131-4136 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maurice,M.M.他: "Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis"Arthritis. Rheum,. 42. 2430-2439 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J.CellPhysiol.: "Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition"J.Cell Physiol.. 182. 33-40 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 熊谷俊一: "酸化ストレスの指標としてのADF/チオレドキシン"臨床病理. 46. 574-580 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura, H. et al.: "Redox regulation of cellular activation."Annu. Rev. Immunol.. 15. 351-369 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi, Y. et al.: "Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat."J. Cerebral Blood Flow and Metabolism. 18. 206-214 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi, Y. et al.: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage."Proc. Natl. Acad. Sci. U. S. A.. 96. 4131-4136 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maurice, M. M. et al.: "Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis."Arthritis Rheum.. 42. 2430-2439 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Isowa, N. et al.: "Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition."J. Cell Physiol.. 182. 33-40 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kumagai, S.: "ADF/thioredoxin as an indicator of oxidative stress"Rinsho Byori. 46. 574-580 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takagi, Y.他: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage"Proc. Natl. Acad. Sci. U.S.A.. 96. 4131-4136 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishiyama, A.他: "Identification of Thioredoxin-binding Protein-2/Vitamin D3 Up-regulated Protein 1 as a Negative Regulator of Thioredoxin Function and Expression"J. Biol. Chem.. 274. 21645-61650 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueno, M.他: "Thioredoxin-dependent redox regulation of p53-mediated p21 activation."J. Biol. Chem.. 274. 35809-35815 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirota, K.他: "Distinct roles of thioredoxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription facor NF-kB"J. Biol. Chem.. 274. 27891-27897 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Bertini, R.他: "Thioredoxin,a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells"J. Exp. Med.. 189. 1783-1789 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maurice, M.M.他: "Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis."Arthritis. Rheum.. 42. 2430-2439 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura,H.: "Measurements of plasma glutaredoxin and thioredoxin in healthy volunteers and during open heart surgery." Free Rad.Biol.Med.24. 1176-1186 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueda,S.: "Redox regulation of caspase-3(-like) Protease activity: regulatory roles of thioredoxin and cytochrome c." J.Immunol.161. 6689-6695 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakamura,H.: "Redox regulation by thioredoxin in host defense." Currrent Trends in Immunology. 1. 133-140 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hotta,M.: "Pancreatic b-cell-specific expression of thioredoxin, an anti-oxidative and anti-apoptotic protein, prevents autoimmune diabetes as well as streptozotocin-induced diabetes." J.Exp.Med.188. 1445-1451 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuki,H.: "Protective effect of Adult T-cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat." Investigative Ophthalmology and Visual Science. 39. 1470-1477 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takagi,Y.: "Redox control of neuronal damage during brain ishemia following middle cerebral artery occlusion in the rat." J.Cerebral Blood Flow and Metabolism. 18. 206-214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ono,K.: "Enhanced expression of hepatocyte growth factor/c-met by myocardial ischemia and reperfusion in a rat model." Circulation. 95. 2552-2558 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ono,K.: "Cytokine gene expression after myocardial infarction in rat hearts.Possible implication in left ventricular remodeling." Circulation. in pewss (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takagi,Y.: "Redox control of neuronal damage during brain ishemia following middle cerebral artery occulusion in the rat." J.Cerebral Blood Flow and Metabolism. 18. 206-214 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okubo,K.: "Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung." Journal of Thoracic Cardiovascular Surgery. 113. 1-9 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakamura,H.: "Redox regulation of cellular activation." Annual Reviews of Immunology. 15. 351-369 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 熊谷俊一: "酸化ストレスの指標としてのADF/チオレドキシン" 臨床病理. (印刷中). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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