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An approach to pathology of psychiatric disorders by a research on the methylation of membrane proteins

Research Project

Project/Area Number 60480263
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionEhime University

Principal Investigator

KAKIMOTO Yasuo  Ehime University (professor), 医学部, 教授 (60028305)

Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1985: ¥3,100,000 (Direct Cost: ¥3,100,000)
KeywordsMembrane protein / Protein N-methylases / Protein carbodymethylases / Calmodulin / schizophrenia / Mania / Adenosylhomocystein / 精神分裂病 / 赤血球 / 向精神薬物 / カルモジュリン / 蛋白質N-メチル化酵素 / メチルリシン / ハイプシン
Research Abstract

While phosphorylation of proteins has been accepted to play essential roles in the regulation of membrane and enzyme functions, biological significance of protein methylation remains unclear in spite of wide occurrences of protein methylation. Nervous systems are the most active organs for protein methylation. We have previously clarified the occurrence of protein methylase of myelin basic protein, and in the present research we found and purified another methylase specific to calmodulin. The enzyme methylates 115 lysine residue of calmoduline obtained from octopus. These proteins are essential proteins for brain stracture and functions.
The activities of two protein carboxymethylases and substrate activities of membrans of erythrocytes were measured in various psychotic and neurological patients. We found an increase in the substrate activity of erythrocytes of manic patients and schizophrenic patients with positive symptoms, which returns to normal value after recovery of the symptoms.
We studied the effects on protein methylation of neutrotransmittors and drugs which modify the synaptic function using the synaptic ending fraction of the rat brain. S-Adenosylhomocystein is a very strong inhibitor which is formed by the reaction of homocystein with intramambrahe adenosine. Regulatory mechanism of protein methylation at synaptic site was suggested.
The last project was directed to study the occurrence of free methylamino acids in the brain. We isolated three methyllysines and three methyl arginines from the TCA extract of the bovine brain. The methods of determination of the methylamino acids were developed to investigate the dynamic state of protein synthesis and degradation.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] M. Mizubuchi;R. Inoue;M. MIyake and Y. Kakimoto: Biochim. Biophys. Acta. 843. 78-82 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] A. Sano;K. Kotani and Y. Kakimoto: J. Neurochem.46(4). 1046-1049 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] T. Innami;M. Miyake and Y. Karimoto: Neurosci. Res.4. 143-151 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] A. Sano;K. Kotani and Y. Kakimoto: J. Neurpchem. 48(3). 681-683 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] M. Miyake and T. Innami: J. Neurochem.49. 355-362 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] H. Morono;T. Kawamoto;M. Miyake and Y. Kakimoto: J. Neurochem.48. 1201-1208 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] M.Mizobuchi, R.Inoue, M.Iyake and Y.Kakimoto: "Accelerated protein turnover in the skeletal muscle of dystrophic mice" Biochim Biophys Acta. 843. 78-82 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] A.Sano, K.Kotani and Y.Kakimoto: "Isolation and identification of <alpha>-<gamma>-(amino-butyryl)-hypusine" J. Neurochem. 46(4). 1046-1049 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] I.Innami, M.Miyake and Y.Kakimoto: "In vitro carboxymethylation of myelin basic protein" Neurosci. Res.4. 143-151 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Sano, K.Kotani and Y.Kakimoto: "Distribution of <alpha>-<gamma>-aminobutyryl)-hypusine" J.Neurochem.48(3). 681-683 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] M.Miyake and T.Innami: "Protein carboxymethylation in synaptic membrane of rat brain: the possible presence of adenosine-S-adenosyl-L-homocysteine hydrolase in the membrane" J.Neurochem.49. 355-362 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] H.Morino, T.Kawamoto, M.Miyake and Y.Kakimoto: "Purification and properties of calmodulin-lysine N-methyltransferase from rat brain cytosol" 48. 1201-1208 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Mizobuchi,M.et al.: Biochim.Biophys.Acta. 843. 78-82 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Sano,A.: J.Neurochem.46. 1046-1049 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Innami,T.et al.: Neurosci.Res.in press. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Morino,H.et al.: J.Neurochem.(1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Sano A.;Imahori et al.(Eds): "Polyamines:Basic and Clinical Aspects" VNU Science Press, 81-88 (1985)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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