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The role of ubiquitin in neuronal apoptosis

Research Project

Project/Area Number 09470290
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokyo

Principal Investigator

KIRINO Takaaki  Department of Neurosurgery, University of Tokyo Hospital Professor, 医学部・附属病院, 教授 (90126045)

Co-Investigator(Kenkyū-buntansha) UEKI Keisuke  Department of Neurosurgery, University of Tokyo Hospital Assistant Professor, 医学部・附属病院, 助手 (20302705)
IDE Takafumi  Department of Neurosurgery, University of Tokyo Hospital Assistant Professor, 医学部・附属病院, 助手 (40262000)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1997: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsubiquitin / apoptosis / cell death / neuron / cerebral ischemia / hippocampus / delayed neuronal death / proteolysis / ラジオイムノアッセイ / ELISA / in situ hybridization
Research Abstract

Ubiquitin content was measured in the gerbil hippocampus following brief cerebral ischemia. Free and conjugated ubiquitin of the CA1 sector and CA3/dendate region are quantitated by radio-immunoassay or ELISA.The result was parallel with our former result by immunostaining. Following transient ischemia, free ubiquitin decreased in CA1 and it never recovered, whereas free ubiquitin transiently decreased in CA3/dentate region and then recovered to the control level within 48 hours. The content of conjugated ubiquitin remarkably increased in both of the regions. It decreased down to the normal level in CA3/dentate region but it maintained a high level at 48 hours following ischemia in CA1. In situ hybridization of ubiquitin mRNA demonstrated a marked increase of signal in the whole area of the hippocampus. Since free ubiquitin never recovered in CA1, translation of ubiquitin mRNA was blocked in this region. On the other hand, ubiquitin mRNA is translated and free ubiquitin rapidly recovered in tolerance-induced hippocampus. Decrease in free ubiquitin results in disturbance of ubiquitin-proteasome proteolytic system. We examined whether the disturbance of ubiquitin-proteasome system is a simple result of cell death process or it is an active process that could contribute to cell degradation. Proteasome activity was inhibited by proteasome inhibitor in cultured rat cortical neurons. The procedure resulted in caspase-3 activation and subsequent neuronal apoptosis. These results indicated that ubiquitin and proteasome are deeply and actively related in the process of delayed neuronal death in the hippocampus.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kawahara N,Ide T,Saito N,Kawai K,Kirino T: "Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor." J Cereb Blood Flow Metab. 18. 472-475 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K, Nakagomi T, Kirino T,Tamura A,Kawai N: "Preconditioning in vivo ischemia inhibits anoxic long-term potentiation and functionally protects CA1 neurons in the gerbil." J Cereb Blood Flow Metab. 18. 288-296 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morikawa E, Mori H, Kiyama Y,Mishina M, Asano T, Kirino T: "Attenuation of focal ischemic brain injury in mice deficient in the epsilon1(NR2A)subunit of NMDA receptor." J Neurosci. 18. 9727-97〓 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ide T, Takada K, Qiu J-H, Saito N,Kawahara N, Asai A, Kirinol T: "Ubiquitin stress response in postischemic hippocampal neurons under non-tolerant and tolerant conditions." J Cereb Blood Flow Metab. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawahara N,Mishima K,H.S,Taniguchi N,Tamura A,Kirino T: "The gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible : its role in ischemia." J Cereb Blood Flow Metab. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 桐野高明: "脳虚血の分子メカニズムと脳保護" 3 興奮毒性と脳保護 山口武典、内山真一郎、松本昌泰、峰松一夫、高木誠編 『脳卒中学』第IV章 医学書院, 10 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 桐野高明: "脳虚血と細胞死" 神経研究進歩 42, 8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawahara N,Ide T,Saito N,Kawai K,Kirino T: "Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor." J Cereb Blood Flow Metab. 18. 472-475 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawai K,Nakagomi T,Kirino T,Tamura A,Kawai N: "Preconditioning in vivo ischemia inhibits anoxic long-term potentiation and functionally protects CA1 neurons in the gerbil." J Cereb Blood Flow Metab. 18. 288-296 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morikawa E,Mori H,Kiyama Y,Mishina M,Asano T,Kirino T: "TAttenuation of focal ischemic brain injury in mice deficient in the epsilon1 (NR2A) subunit of NMDA receptor." J Neurosci. 18. 9727-9732 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ide T,Takada K,Qui J-H,Saito N,Kawahara N,Asai A,Kirino T: "TUbiquitin stress response in postischemic hippocampal neurons under non-tolerant and tolerant conditions." J Cereb Blood Flow Metab. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawahara N,Mishima K,Higashiyama S,Taniguchi N,Tamura A,Kirino T: "The gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible : its role in ischemia." J Cereb Blood Flow Metab. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kirino T: "Molecular mechanism in cerebral ischemia and brain protection" Igakushoin, Strokology Chapter IV. 236-245 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kirino T: "Cerebral ischemia and cell death" Advances in Neurological Sciences. 42. 977-984 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawahara N,Ide T,Saito N,Kawai K,Kirino T: "Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor." J Cereb Blood Flow Metab. 18. 472-475 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawai K,Nakagomi T,Kirino T,Tamura A,Kawai N: "Preconditioning in vivo ischemia inhibits anoxic long-term potentiation and functionally protects CA1 neurons in the gerbil." J Cereb Blood Flow Metab. 18. 288-296 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morikawa E,Mori H,Kiyama Y,Mishina M,Asano,Kirino T: "Attenuation of focal ischemic brain injury in mice deficient in the epsilon1(NR2A)subunit of NMDA receptor." J Neurosci. 18. 9727-9732 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 桐野高明: "脳虚血の分子メカニズムと脳保護" 医学書院『脳卒中学』第IV章, 10 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 桐野高明: "脳虚血と細胞死" 神経研究進歩 42, 8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川合謙介、 桐野高明: "前脳虚血モデルにおける低脳温の効果" 集中治療. 9. 627-634 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 桐野高明: "脳虚血とその治療可能性について" Brain Hypoxia. 11. 93-111 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kirino T: "Ischemic tolerance Primer on Cerebrovascular Diseases." Academic Press Welch KMA,Caplan LR,Reis DJ,Siesjo BK,Weir B(Eds), 4 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ide T, Morimoto T, Kirino T: "Transient ischemia depletes free ubiquitin in the gerbil hippocampal CA1 neurons.Maturation Phenomenon in Cerebral Ischemia II." Springer Ito U,Kirino T,Kuroiwa T,Klatzo I(Eds), 5 (199)

    • Related Report
      1997 Annual Research Report

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

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