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Development, application, and generalization of new methodology to spatially resolve proteolytic phenomena.

Research Project

Project/Area Number 06557131
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Biological pharmacy
Research InstitutionTOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE

Principal Investigator

SAIDO Takaomi C  Tokyo Metropolitan Institute of Medical Science, Department of Molecular Biology, Research Scientist, 遺伝情報研究部門, 研究員 (80205690)

Co-Investigator(Kenkyū-buntansha) SHIBATA Masao  Medical and Biological Laboratory, Inc., Department of Medicine, Chief, 医薬開発研究室, 室長
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsPROTEOLYSIS / PROTEASE / CALPAIN / FODRIN / ISCHEMIA / beta-AMYLOID / AGING / ALZHEIMER'S DISEASE / プロテオリミス / フキドリン / フオドリン
Research Abstract

Biological science has long suffered from the technical inability to spatially resolve proteolytic phenomena ; orthodox methods require sample homogenization resulting in loss of spatial information that could reveal where in cells or tissues a proteolytic reaction of interest takes place. Efforts have thus been made to overcome this obstacle by developing antibodies that distinguish a proteolyzed form of a given protein from its intact form. The methodology for such an approach has been generalized and is used as a powerful tool to resolve proteolytic phenomena such as calpain-catalyzed proteolysis in brain ischemia and processing of beta-amyloid peptide associated with Alzheimer's disease. Newly obtained information by this method is likely to contribute to developint preventive and therapeutic measures against these neurodegenerative disorders.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Saido,T.C. 他: "Spntial resolution of the primary B-amyloidogenic process indnced in postischemic brain" J.Biol Chem.269. 15253-15257 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido,T.C. 他: "Calpain : new perspoctives in molecmlar diversity and physiological-pathological involvemont." FASEB J.8. 814-822 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido,T.C. 他: "Dominant and atterantial deposition of distinct B-amyloid peptide species,AB N3(PE),in senile playnes" Neuron. 14. 457-466 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido,T.C. 他: "Amino-and carboxyl-terominal heterogeneity of B-amyloid peptides deposited in human brain" Neuron Leth.215. 173-176 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuda,T. 他: "Reduction of plasma glntomyl an nopeptidase activity in sporadic Alzheilner's discase" Biochem.Biophys.Res.Commun. 231. 526-530 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido,T.C.: "Alzheimer's disease as proteolytic disorders : prodnction and catabolism of B-any loid." Neurobiol.Aging. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 西道隆臣・丸山敬: "アルツハイマー病の分子医学" 中外医学社, 114 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yokota, M., Saido, T.C., Miyaji, K., Tani, E., Kawashima, S., Suzuki, K.: "Stimulation of protein-tyrosine phosphorylation in gerbil hippocampus after global forebrain ischemia" Neurosci. Lett.168. 69-72 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagao, S., Saido, T.C.(corresponding author), Akita, Y., Tsuchiya, T., Suzuki, K., Kawashima, S.: "Calpain-calpastatin interactions in epidermoid carcinoma KB cells." J.Biochem.115. 1178-1184 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sorimachi, H., Saido, T.C., Suzuki, K: "New era of calpain research, discovery of tissue-specific calpains" FEBS Lett.343. 1-5 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C., Nagao, S., Shiramine, M., Tsukaguchi, M., Yoshizawa, T., Sorimachi, H., Ito, H., Tsuchiya, T., Kawashima, S., Suzuki, K.: "Distinct kinetics of subunit autolysis in mammalian m-calpain activation" FEBS Lett.346. 263-267 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C., Sorimachi, H., Suzuki, K.: "Calpain : new perspectives in molecular diversity and physiological-pathological involvement" FASEB J.8. 814-822 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C., Yokota, M., Maruyama, K., Yamao-Harigawa, W., Tani, E., Ihara, Y., Kawashima, S.: "Spatial resolution of the primary beta-amyloidogenic process induced in postischemic brain." J.Biol. Chem.269. 15253-15257 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshida, K., Inui, M., Harada, K., Saido, T.C., Sorimachi, Y., Ishihara, T., Kawashima, S., Sobue, K.: "Reperfusion of rat heart after brief ischemia induces proteolysis of calspection (non-erythroid spectrin or fodrin) by calpain" Circ. Res.77. 603-610 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Blomgren, K., Kawashima, S., Saido, T.C., Karlsson, J.-O., Hagberg, H.: "Subcellular distribution of calpains and fodrin degradation after neonatal hypoxic ischemia" Brain Res.684. 143-149 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bloomgren, K., McRae, A., Bona, E., Gilland, E., Saido, T.C., Karlsson, J.-O., Hagberg, H.: "Degradation of fodrin and MAP2 after neonatal cerebral hypoxic-ischemia." Brain Res.684. 136-142 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bednarski, E., Vanderklish, P., Gall, C., Saido, T.C., Bahr, B.A., Lynch, G.: "Translational suppression of calpain I reduces NMDA-induced spectrin proteolysis and pathophysiology in cultured hippocampal slices." Brain Res.694. 147-157 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Vanderklish P., Saido T.C., Gall, C., Arai, A., Lynch, G.: "Proteolysis of spectrin by calpain accompanies theta-burst stimulation in cultured hippocampal slices" Mol. Brain Res.32. 25-35 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Harigaya, Y., Shoji, M., Kawarabayashi, T., Kanai, M., Nakamura, T., Iizuka, T., Igeta, Y., Saido, T.C., Sahara, N., Mori, H., Hirai, S.: "Modified amyloid beta-protein ending at 42 or 40 with different solubility accumulates in the brain of Alzheimer's disease." Biochem. Biophys. Res. Commun.211. 1015-1022 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yokota, M., Saido, T.C., Tani, E., Kawashima, S., Suzuki, K.: "Three distinct phases of fodrin proteolysis induced in postischemic hippocampus : involvement of calpain and unidentified protease" Stroke. 26. 1901-1907 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Igarashi, K., Kaneda, M., Yamaji, A., Saido, T.C., Kikkawa, U., Ono, Y., Inoue, K., Umed, M.: "A novel phospatidylserine-binding peptide motif defined by an anti-idiotypic monoclonal antibody : localization of phosphatidylserine-specific binding sites on protein kinase C and phosphatidylserine decarboxylase." J.Biol. Chem.270. 29075-29078 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Martin, S.J., O'Brien, G.A., Nishioka W.K., Mahboubi, A., Saido, T.C., Green, D.R.: "Proteolysis of fodrin (nonerythroid spectrin) during apoptosis." J.Biol. Chem.270. 6425-6428 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Du, X., Saido, T.C.(two first authors), Tsubuki, S., Indig, F.E., Williams, M.. J., Ginsberg, M.H.: "Calpain cleavage of the cytoplasmic domain of the integrin beta3 subunit." J.Biol. Chem.270. 24146-26152 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C., Iwatsubo, T., Mann, D.M.A., Shimada, H., Ihara, Y., Kawashima, S.: "Dominant and differential deposition of distinct beta-amyloid peptide species, AbetaN3 (pE), in senile plaques" Neuron. 14. 457-466 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamashima, T., Saido, T.C., Takita, M., Miyazawa, A., Yamano, J., Miyakawa, A., Nishijo, H., One, T., Yamashita J., Yoshioka, T.: "Transient brain ischemia provokes Ca2+ mobilization, PIP2 overexpression and calpain activation prior to delayd CA-1 neuronal death in monkeys." Eur. J.Neurosci.8. 1932-1944 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inomata, M., Hayashi, M., Ohno-Iwashita, Y., Tsubuki, S., Saido, T.C., Kawashima, S.: "Involvement of calpain in integrin-mediated signal transduction." Arch. Biochem. Biophys. 328. 129-134 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kanai, Y., Kanai-Azuma, M., Noce, T., Saido, T.C., Shiroishi, T., Hayashi, Y., Yazaki, K.: "Identification of two Sox 17 mRNA isoforms, with and without the HMG-box region, and their differential expression in mouse spermatogenesis." J.Cell Biol.133. 667-681 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Lemere, C.A., Blusztajn, J.K., Yamaguchi, H., Wisniewski, T., Saido, T.C., Selkoe, D.J.: "Sequence of deposition of heterogeneous amyloid beta-peptides and apo E in Down syndrome : implications for initial events in amyloid plaque formation." Neurobiol. Disease. 3. 16-32 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yokota, M., Saido, T.C., Tani, E., Yamaura, I., Minami, N.: "Cytotoxic fragment of amyloid precursor protein accumulates in hippocampus after global forebrain ischemia." J.Cereb. Blood Flow Metabol.16. 1219-1223 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saito, Y., Maruyama, K., Kawano, J., Yamagishi, K., Saido, T.C., Kawashima, S.: "Molecular cloning and characterization of a novel form of neuropeptide precursor gene as a developmentally regulated molecule." J.Biol. Chem.271. 15615-15622 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C., Yamao-Harigawa, W., Iwatsubo, T., Kawashima, S.: "Amino- and carboxyl-terminal heterogeneity of beta-amyloid peptides deposited in human brain" Neurosci. Lett.215. 173-176 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwatsubo, T., Saido, T.C., Mann, D.M.A., Lee, V.M.-Y., Trojanowski, J.Q.: "Full-length Abeta(1-42 (43)) as well as amino-terminally modified and truncated Abeta42 (43) deposit in diffuse plaques." Am. J.Pathol.149. 1823-1830 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Lemere, C.A., Lopera, F., Kosik, K.S., Lendon, C.L., Ossa, J., Saido, T.C., Yamaguchi, H., Ruiz, A., Martinez, A., Madrigal, L., Hincapie, L., Arango L., J.C., Anthony, D.C., Koo, E.H., Goate, A.M., Selkoe, D.. J., Arango v., J.C.: "The E280A Presenilin 1 mutation leads to a distinct Alzheimer's disease phenotype : Increased Abeta42 deposition and severe cerebellar pathology" Nature Medicine. 2. 1146-1150 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Maruyama, K., Tomita, T., Shinozaki, K., Kume, H., Asada, H., Saido, T.C., Ishiura, S,Iwatsubo, T., Obata, K.: "Familial Alzheimer's disease-linked mutations at Val717 of amyloid precusor protein are specific for the increased secretion of Abeta42 (43)" Biochem. Biophys. Res. Commun.227. 730-735 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Blomgren, K., McRae, A., Elmered, A., Kawashima, S., Saido, T.C., Hagberg, H.: "The calpain proteolytic system in neonatal hypoxic-ischemia." Ann. New York Acad. Sci.(in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuda, T., Shoji, M., Arai, H., Kawashima, S., Saido, T.C.: "Reduction of plasma glutamyl aminopeptidase activity in sporadic Alzheimer's disease" Biochem. Biophys. Res. Commun.231. 526-530 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tomita, T., Maruyama, K., Saido, T.C., Kume, H., Shinozaki, K., Tokuhiro, S., Capell, A., Walter, J., Gruenberg, J., ; Haass, C., Iwatsubo, T., Obata, K: "The presenilin 2 mutation (N141I) linked to familial Alzheimer's disease (Volga German families) increases the secretion of amyloid beta protein ending at Abeta42 (43)." Proc. Nat. Acad. Sci. USA. 94. 2025-2030 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mann, D.M.A., Iwatsubo, T., Pickering-Brown, S.M., Owen, F., Saido, T.C., Perry, R.H.: "Preferential Deposition of amyloid beta protein (Abeta) in the form of Abeta40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele." Neurosci. Lett.221. 81-84 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mann, D.M.A., Pickering-Brown, Byatt, N.N., Wright, A.E., Owen, F., Iwatsubo, T., Saido, T.C.: "An intronic polymorphism in the presenilin-1 gene does not influence the amount or molecular form of the amyloid beta protein deposited in Alzheimer's disease." Neurosci. Lett.222. 57-60 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C.: "Alzheimer's disease as proteolytic disorders : Production and catabolism of beta-amyloid" Neurobiol. Aging. (in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saido, T.C., Yokota, M., Tani, E., Kawashima, S.: Post-secretory catabolism of beta-amyloid in brain. in Alzheimer's Disease : Biology. Diagnosis and Therapeutics (Iqbal, K., Winblad, B., Nishimura, T., Takeda, M., Wisniewski, H.M., eds.), John Wiley & Sons Ltd. (Chichester), 339-348 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inomata,M.他: "Involvemert of calpain in integrin-mediated signal transduction." Akch.Biochem.Biophys.328. 129-134 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokota,M.他: "Cytotoxic fragment of amyloid preursor protein accumulates in hippocampus after global forebrain ischernia" J.Careb.Blood Flow Metahol.16. 1219-1223 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saido,T.C.他: "Amino-and Carboxyl-terminal heterogenaity of β-amyloid peptides deposited in human broin." Ncurosci Lett.215. 173-176 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Leinere,cA.他: "The E280A presonilin I mutation Leads to a atistinot Alzheimers d : 4use phenotype : Increased Aβ42 deposition and sevore ceroballar pothology." Nature Mediicine. 2. 1146-1150 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kuda,T.他: "Reduction of plasrne glntamyl aminopepticlase activity in sporadic Alzheimers disease" Biochen.Biophys.Res.Commun.231. 526-530 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saido,T.C.: "Alzheimers discase as protcolytic disorters : prooluction and catabolism of β-amyloid" Neurobior.Aging. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 西道隆臣・丸山敬: "アルツハイマー病の分子医学" 中外医学社, 114 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Martin, S. J. 他: "Proteoiysis of fodrin (nonerythroid spectrin) during apoptosis." J. Biol. Chem.270. 6425-6428 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Du, X., Saido T. C. 他: "Calpain cleavage of the cytoplasmic domain of the integrin B3 subunit." J. Biol. Chem.270. 24146-26152 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Eto, A. 他: "The role of the calpain-calpastatin system in thyrotropin-releasing hormone-induced selective down-regulation of a protein-kinase-C isozyme, npkce." J. Biol. Chem.270. 25115-25120 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yokota, M., Saido T. L. 他: "Three drstinct phases of fodrin proteclysis indrad in paslischemic hippo campus" Stroke. 26. 1901-1907 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saido T. C. 他: "Dominant and difflential deposition of distinct β-amyloid peptide species, Α β N3(PE), in senile plaques." Neuron. 14. 457-466 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Inomata 他: "Involvement of calpain in integrin-mediated signal transduction." Arch. Biochem. Biophys.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saido,T.L.他: "Dominant and differential deposition of distinct B-amyloid peptide species, ABN3(p5),in semile plaques" Neuron. 14. 457-466 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Saido,T.C.他: "Spatial resolution of the primary B-amyloidogenic process induced in postischemic brain" J.Biol.chem.269. 15253-15257 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Saido,T.l.他: "Calpain:new perspeotives in molecular diversity and physiological-pathological involvement" FASEB J.8. 814-822 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Saido、T.C.他: "Distinct kinetics of subunit autolysis in nammalian m-calpain activation" FEBS Lett.346. 263-267 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sorimachi,H 他: "New era of calpain research,discovery of tissue-specitic calpains" FEBS Lett.343. 1-5 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagao,S他: "Calpain-calpastatin interactions in epidermoid carcinoma KB cells" J.Biochem.115. 1178-1184 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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