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Biochemical studies on the mechanism of Generation and accumulation of altered enzymes with age

Research Project

Project/Area Number 63480467
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionToho University, School of Pharmaceutical Science

Principal Investigator

GOTO Sataro  TOHO UNIV. SCH, PHAM. PROFESSOR, 薬学部, 教授 (10012650)

Co-Investigator(Kenkyū-buntansha) MOTOJIMA Kiyoto  LECTURER, 薬学部, 講師 (70166338)
TAKAHASHI Ryoya  RES. ASSOCOCIATE, 薬学部, 助手 (40197190)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥4,500,000 (Direct Cost: ¥4,500,000)
KeywordsAging / Altered enzyme / Protein Degradation / 活性酸素 / 肝実質細胞
Research Abstract

(1) We performed model experiments where partially purified aminoacyl tRNA synthetases are incubated with active oxygen producing systems. A part of the enzymes was rendered heat-labile, thus mimicking "old" enzymes in terms of heat-inactivation profiles. It is therefore suggested that active oxygens might be involved in the generation of altered proteins.
(2) We demonstrated that half-lives of proteins microinjected into mouse hepatocytes in primary culture as well as intracellularly labeled proteins are extended by 50 to 60% in the cells from old animals. It is therefore suggested that accumulation of altered proteins in senescent animals is partly due to decrease in the turnover of proteins.
(3) Twenty third month-old mice were subjected to dietary restriction for 2 months, and then proportion of heat-labile enzymes and half-life of proteins were examined. Proportion of heat-labile enzymes was decreased to a level of young animals and so are the half-lives of proteins.Thus it is suggested that anti-aging effect of dietary restriction is at least partly to "rejuvenate" decreased protein metabolism that occur with age.
(4) Using anti-ubiquitin antibody we measured amounts of free and conjugated ubiquitin in the brain, liver and kidney of young and old mice. The amount of free ubiquitin in the brain was decreased by about 40% in the old animals but not in the other tissues. Conjugated forms of ubiquitin was increased significantly in the old brains but not in other tissues. The turnover of altered proteins is thus suggested to decrease in the brain of old animals.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] S.Kobayashi: "Nucleotide sequence of mouse genomic DNA sequence for a brain specific small RNA." Nucleic Acid Res.,. 16. 360 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Horikoshi,T: "Taurine and β-alanine act on both GABA and glycine receptors in Xenopus oocyte injected with mouse brain messenger RNA." Mol.Brain Res.,. 4. 97-105 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Horikoshi,T: "Taurine modulates glycine rseponse in Xenopus oocytes injected with messenger RNA from mouse brain" Mol.Brain Res.,. 4. 243-246 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima,K.: "A human genomic sequence highly homologous to the 3'-untranslated region of rat uricase mRNA" Biochem.Biophys.Res.Comm.,. 155. 1266-1270 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima,K.: "Cloning and sequence analysis of cDNA for rat liver uricase," J.Biol.Chem.,. 263. 16677-16681 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishigami,A.: "Inactivation kinetics of horseradish peroxidase microingjected into hepatocytes from mice of various ages" Mech.Ageing Dev.,. 46. 125-133 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takahashi,R.: "Fidelity of aminoacylation by rat liver tyrosyl tRNA synthetase:Effect of age" Eur.J.Biochem.,. 178. 381-386 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima,K.: "Coning of rabbit uricase cDNA reveals a conserved carboxyterminal tripeptide in three species" Biochem.Biophys.Acta. 1008. 116-118 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Horikoshi,T.: "Regional distribution of metabotrophic glutamate response in the rat brain using Xenopus oocytes" Neuroscience letters. 105. 340-343 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima,K.: "Brain-specific expression of transthyretin mRNA as revealed by cDNA cloning from brain" FEBS lteers. 258. 103-105 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishigami,A.: "Age-related change in the degradation rate of ovalbumin microijected into mouse liver parenchymal cells" Arch.Biochem.Biophys.,. 277. 189-195 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takahashi,R.: "Alteration of aminoacyl-tRNA synthetase with ag:Heatlabilization of the enzyme by oxidative damage" Arch.Biochem.biophys.277. 228-233 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 後藤佐多良: "老化はなぜ起るか:細胞と分子からみた老化のしくみ" 化学と工業. 41. 110-113 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 後藤佐多良: "老化研究モデル系" ファルマシア. 24. 688-690 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 後藤佐多良: "老化による生体機能の変化" 薬局. 40. 1099-1103 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 後藤佐多良: "動物の老化とヒトの老化-そのしくみと制御(1)" 日本薬剤師会雑誌. 41. 573-582 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 後藤佐多良: "動物の老化とヒトの老化-そのしくみと制御(2)" 日本薬剤師会雑誌. 41. 941-953 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 後藤佐多良: "加齢と老化-老化の基礎科学「老化と寿命」" GERONTOLOGY-NEW HORISON. (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] "バイオサイエンス戦略マニュアル-新しい素材とマ-カ-・プロ-ブ(印刷中)" 共立出版, (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 太田邦夫: "老化指標デ-タブック(共著)" 朝倉書店, 334 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 濱堯夫: "機能生化学(共著)" 朝倉書店, 278 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S.Kobayashi, Anzai, K. and Goto, S.: "Nucleotide sequence of mouse genomic DNA sequence for brain specific small RNA" Nucleic acid Res. 16 (1988) 36.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Horikoshi, T., Asanuma, A., Yanagisawa, K. Anzai, K. and Goto, S.: "Taurine and beta-alanine act on both GABA and glycine receptors in Xenopus oocyte injected with mouse brain messenger RNA" Mol.Brain Res. 4 (1988) 97-105.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Horikoshi, T., Asanuma, A., Yanagisawa, K. and Goto, S.: "Taurine modulates glycine response in Xenopus oocytes injected with messenger RNA from mouse brain" Mol.Brain Res. 4 (1988) 243-246.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima, K. and Goto, S.: "A human genomic sequence highly homologous to the 3' -untranslated region of rat uricase mRNA" Biochem.Biophys. Res.Comm. 155 (1988) 1266-1270.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima, K., Kanaya, S. and Goto, S.: "Cloning and sequence analysis of cDNA for rat liver uricase" J.Biol.Chem.263 (1988) 16677-16681.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishigami, A. And Goto, S.: "Inactivation kinetics of horseradish peroxidase microinjected into hepatocytes from mice of various ages" Mech.Ageing Dev. 46 (1988) 125-133.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takahashi, R. and Goto, S.: "Fidelity of aminoacylation by rat liver tyrosyl tRNA synthetase: Effect of age" Eur.J.Biochem. 178 (1988) 381-386.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima, K. and Goto, S.: "Cloning of rabbit uricase cDNA reveals a conserved carboxy-terminal tripeptide in three species" Biochim.Biophys. Acta 1008 (1989) 116-118.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Horikoshi, T., Asanuma, A., Yanagisawa, K., Anzai, K. and Goto, S.: "Regional distribution of metabotrophic glutamate response in the rat brain using Xenopus oocytes" Neurosci.Lett. 105 (1989) 340-343.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Motojima, K. and Goto, S.: "Brain-specific expression of transthyretin mRNA as revealed by cDNA cloning from brain" FEBS Lett. 258 (1989) 103-105.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ishigami, A. and Goto, S.: "Age-related change in the degradation rate of ovalbumin microinjected into mouse liver parenchymal cells" Arch.Biochem. Biophys. 277 (1990) 228-233.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takahashi, R. and Goto, S.: "Alteration of aminoacyl-tRNA synthetase with age: Heat-labilization of the enzyme by oxidative damage" Arch.Biochem. Biophys.277 (1990) 228-233.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Motojima,S.Goto: "Cloming of rabbit wicese cDNA reveals a conservative carboxy terminal tropeptide in these spcecne" Biochem.Biophys.A to. 1008. 116-118 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Hoshoshi,et al(S.Goto): "Regonal dishibntion of motabotropic glutamete veponrs in the rat lren wing ret brain using xenopus on cytel" Neuros sence letters. 105. 340-343 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Motojima,S.Goto: "Brasーmpecfie expuson of trestbyretin mRNA as sevealed by CDNA cloukcy from freie" FEBS Letters. 258. 103-105 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] R.Takahashi,S.Goto: "Alteatron of cmuoamgl teaA mywhetase with age:heatーlabolyetion of he engpne" Asoch.Biochem.Biophys. 277. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] A.Ishigame,S.Goto: "Age related cheye in the degredation rate of ovalbumin moroyeted into mase" Arel.Biochem Biophys. 277. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] A.Ishigami.: Mech.Ageing Dev.,. 46. 125-133 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] R.Takahashi.: Europ.J.Biochem.,. 178. 381-386 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] K.Motojima.: J.Biol.Chem.,. 263. 16677-16681 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] K.Anzai.: Mol.Brain Res.,. 4. 273-281 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] S.Goto.: Trecds in Biomedical Gerontology. 1. 197-199 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] S.Kobayashi.: Nucleic Acies Res.,. 16. 360 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 後藤佐多良 他: "老化指標データブック" 朝倉書店, 334 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 後藤佐多良 他: "機能生化学" 朝倉書店, 278 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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