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Development of a method for early diagnosis of diabetic of complications by detecting glycation reaction intermediates.

Research Project

Project/Area Number 09557017
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pathological medical chemistry
Research InstitutionOsaka University

Principal Investigator

FUJII Junichi  Osaka University Medical School, Associate Professor, 医学部, 助教授 (00222258)

Co-Investigator(Kenkyū-buntansha) ITOH Satoru  Fujirebio, Inc.Diagnostic Research Laboratories, General Manager, 検査薬研究所, 室長
TANIGUCHI Naoyuki  Osaka University Medical School, Professor, 医学部, 教授 (90002188)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsDiabetic complicatrions / Glycation / Crystallin / Glucose / Fructose / Polyol pathway / Cataract
Research Abstract

Glycation occurs during normal aging and at accelerated rates in diabetes and is involved in structural and functional alterations of proteins and other cellular components. In terms of diabetic complications, the glycation hypothesis and the poiyol pathway hypothesis are usually discussed independently. An antibody was raised against fructated lysine in proteins by immunizing fructated lysine-conjugated ovalbumin in rabbits. The affinity purified antibody specifically recognized proteins incubated with fructose, but not with glucose. When bovine serum albumin was incubated with various concentrations of fructose, the reactivity of thee antibody increased in a dose- and time-dependent manner. When soluble proteins prepared from either normal or streptozotocin-induced diabetic rat eyes were analyzed by ELISA using this antibody, an increase in the reactive components was observed as a function of aging as well as under diabetic conditions. Immunoblot analysis showed that lens crystallin reacted highly with this antibody. Since fructose is largely biosynthesized through the polyol pathway, which is enhanced under diabetic conditions and lens is known to have a high activity of this pathway, this antibody is capable of recognizing fructated proteins in viva. Thus this antibody represents a potentially useful tool for investigating two major issues which appear to be involved in diabetic complications, namely, the glycation reaction and the polyol pathway.

Report

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

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Asahi,M: "The oxidation of selenocysteine is involved in the inactivation of glutathione peroxidase by nitric oxide donor." J Biol Chem. 272. 19152-19157 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto,A: "A high expression of heme oxygenase-1 in the liver of LEC rats at the stage of hepatitis ; the possible implication of induction in uninvolved tissues." Free Radic Res. 28. 383-391 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujii,J: "A defect in the mitochondrial import of mutant Mn-superoxide dismutase produced in Sf21 cells." J Biochem. 124. 340-346 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hatanaka,Y: "Reactive oxygen species enhances the induction of onducible nitric oxide synthase by sphingomyelinase in RAW264.7 cells." Biochim Biophys Acta. 1393. 203-210 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyazawa,N: "Immunological detection of fructated proteins in in vitro and in vivo." Biochem J. 336. 101-107 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawasaki,Y: "Specific detection of the early process of the glycation reaction by fructose and glucose in diabetic rat lens." FEBS Lett. 441. 116-120 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Fujii: "Pathophysiology of Lipid Peroxides and Related Free Radicals(K.Yagi ed.)" Japan Scientific Societies Press,Tokyo, 10 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Fujii: "Medical Biochemistry(Dominiczak MH,and Baynes JW eds.)" Mosby,London(in press), (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Asahi: "the oxidation of selenocysteine is involved in the inactivation of glutathione peroxidase by nitric oxide donor." J Biol Chem. 272. 19152-19157 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Matsumoto: "A high expression of heme oxygenase-1 in the liver of LEC rats at the stage of hepatitis ; the possible implication of induction in uninvolved tissues." Free Radic Res. 28. 383-391 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] J.Fujii: "A defect in the mitochondrial import of mutant Mn-superoxide dismutase produced in Sf21 cells." J Biochem. 124. 340-346 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hatanaka: "Reactive oxygen species enhances the induction of onducible nitric oxide synthase by sphingomyelinase in RAW264.7 cells." Biochim Biophys Acta. 1393. 203-210 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Miyazawa: "Immunological detection of fructated proteins in in vitro and in vivo." Biochem J. 336. 101-107 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawasaki: "Specific detection of the early process of the glycation reaction by fructose and glucose in diabetic rat lens." FEBS Lett. 441. 116-120 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsumoto,A: "A high expression of heme oxygenase-1 in the liver of LEC rats at the stage of hepatitis;the possible implication of induction in uninvolved tissues." Free Radic Res. 28. 383-391 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koizumi,M: "A marked increase in free copper levels in the plasma and liver of LEC rats:an animal model of Wilson disease and liver cancer." Free Radic Res. 28. 441-450 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujii,J: "A defect in the mitochondrial import of mutant Mn-superoxide dismutase produced in Sf21 cells." J Biochem. 124. 340-346 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hatanaka,Y: "Reactive oxygen species enhances the induction of onducible nitric oxide synthase by sphingomvelinase in RAW264.7 cells." Biochim Biophys Acta. 1393. 203-210 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Watanabe T: "Dysfunction of antioxidative enzymes in the trinitrobenzensulfonic acid-induced coliltis rat." Pathophysiology. 5. 191-198 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyazawa N: "Immunological detection of fructated proteins in in vitro and in vivo." Biochem J. 336. 101-107 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Fujii.: "Pathophysiology of Lipid Peroxides and Related Free Radicals" Japan Scientific Societies Press,Tokyo, 10 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Fujii.: "Medical Biochemistry(Dominiczak MH,and Baynes JW eds.)" Mosby,London(in press), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Asahi: "The oxidation of selenocysteine is involved in the inactivation of glutathione peroxidase by nitric oxide donor." J.Biol.Chem.272. 19152-19157 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.G.Seo: "Roles of purine nucleotides and adenosine in enhancing NOSII dene expression in interleukin-1 β-stimulated rat vascular smoothmuscle cells." Free Radic.Res.26. 409-418 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.N.Islam: "TGF-β triggers oxidative modification and enhances apoptosis in HIT-cells through accumulation of reactive oxygen species by suppression of catalase and glutathione. peroxidase." Free Radic.Biol.Med.22. 1007-1017 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Fujikado: "THe effect of nitric oxide synthase inhibitor on the form deprivation myopia." Curr.Eye Res.16. 992-996 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] J.Fujii: "Pathophysiology of Lipid Peroxides and Related Free Radicals"(Yagi,K.ed)" Japan Sci.Soc,Press,Tokyo, 10 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Taniguchi: "Oxidative Stress in Cancer,AIDS,and Neurodegenerative Diseases"(L.Montagnier,R.Olivier,and C.P.asquier eds)" Marcel Dekker,Inc.New York, 6 (1998)

    • Related Report
      1997 Annual Research Report

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

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