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Detection of the activation of caspases during neuronal cell death by using antiserum specifically recognizing active form of caspases

Research Project

Project/Area Number 11480235
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNational Institute of Neuroscience

Principal Investigator

MOMOI Takashi  National Institute of Neuroscience Div. Development and Differentiation, Lab. Head, 神経研究所・疾病研究第5部, 室長 (40143507)

Co-Investigator(Kenkyū-buntansha) 内山 安男  大阪大学, 大学院医学系・研究科・情報伝達医学機能形態学, 教授 (10049091)
塚原 俊文  国立精神・神経センター, 神経研究所・疾病研究第1部, 研究員 (60207339)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
Keywordsapoptosis / caspase-12 / ER stress / polyglutamine disease / Huntinton / Endoplasmic Reticulum / processing / Neurodegenerative disease / カスパーゼー12 / ER ストレス / ハンチントン病 / ポリグルタミン / カスパーゼ12 / 神経細胞死 / 脳形成 / カスパーゼ9 / カスパーゼ3 / Bcl-x / ミトコンドリア / チトクロームC / Akt / BMP-4 / レチノイン酸
Research Abstract

Considerable evidence suggests that caspase, a member of cystein protease, plays an essential role in the various cell death including apoptosis and programmed cell death (PCD) and in the cell death observed in the various diseases. However, there is little direct evidence on the involvement of caspases in naturally occurring cell death during development of the vertebrate nervous system and diseases. Caspases are sequentially activated in the caspase cascade, in which activated initial caspases such as caspase 9, caspase 8 and caspase 12 are autoprocessed and then process caspase 3, 6 and 7. To clarify the involvement of caspases in the PCD and neurodegenerative diseases, we prepared cleavage site-directed antiserum against 12 members of caspases that specifically react with the cleaved fragment of caspases, respectively. We have examined directly the activation of caspases during development of mouse embryos and subcellular localization of active form of caspases by immunohistochemical staining using these antisera.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Momoi, T., Fujita, E., Urase, K.: "Strain-specific caspase-3-dependent programmed cell death in the developing forebrain"Neuroreport. 14. 111-115 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jimbo, A., Fujita, E., Kouroku, Y., Ohnishi, J., Inohara, N., Kuida, K., Sakamaki, K., Yonehara, S., Momoi, T.: "ER stress induces caspase-8 activation stimulating the cytochrome c release and caspase-9 activation"Exp.Cell.Res.. 283. 156-166 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita, E., Kouroku, Y., Jimbo, A., Maruyama, K., Momoi, T.: "Caspase-12 processing and fragment translocation into nuclei of tunicamycin-treated cells"Cell Death Differ.. 9. 1108-1114 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouroku, Y., Fujita, E., Jimbo, A., Kikuchi, T., Yamagata, T., Momoi, MY, Kominami E., Kuida, K., Sakamaki, K., Yonehara, S., Momoi, T.: "Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation"Hum.Mol.Genet.. 11. 1505-1515 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita, E., Egashira, J., Urase, K., Kuida, K., Momoi, T.: "Caspase-9 processing via feedback amplification loop in vivo"Cell Deth and Differentiation. 8. 335-344 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi, K., Kamiya, K., Urase, K., Fujita, E., Suga, M., Mori, H., Yoshikawa, Y., Ichimura, K., Kuida, K., Momoi, T.: "Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of sensory cells resulting in the hearing loss"Brain Res.. 894. 359-367 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouroku Y, Fujita E, Urase K, Tsuru T, Setsuie R, Kikuchi T, Yagi Y, Momoi MY, Momoi T.: "Caspase that are activated during generation of nuclera pologlutamine aggregates are necessary for DNA fragmentation but not suffiviennt for cell death"J Neurosci Res.. 62. 547-556 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita E, Urase K, Egashira J, Miho Y, Isahara K, Uchiyama Y, Isoai A, Kumagai H, Kuida K, Motoyama N, Momoi T.: "Detection of caspase-9 activation in the cell death of the Bcl-x-deficient mouse embryo nervous system by cleavage sites-directed antisera"Brain Res Dev Brain Res.. 122. 135-147 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouroku Y, Fujita E, Jimbo A, Mukasa T, Tsuru T, Momoi MY, Momoi T.: "Localization of active form of caspase-8 in mouse L929 cells induced by TNF treatment and polyglutamine aggregates"Biochem Biophys Res Commun. 270. 270,972-977 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita E, Soyama A, Kuwabata M, Momoi T: "BMP-4 and retinoic acid synergistically induce activation of caspase-9 and cause apoptosis of P19 embryunal carcinoma cells cultured as a monolayer"Cell Death Differ.. 6. 1109-1116 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Momoi, T., Fujita, E., and Urase, K.: "Strain-specific caspase-3-dependent programmed cell death in the developing forebrain"Neuroreport. 14. 111-115 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jimbo, A., Fujita, E., Kouroku, Y., Ohnishi, J., Inohara, N., Kuida, K., Sakamaki, K., Yonehara, S., and Momoi, T.: "ER stress induces caspase-8 activation stimulating the cytochrome c release and caspase-9 activation"Exp. Cell Res.. 283. 156-166 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujta, E., Kouroku, Y., Jimbo, A., Maruyama, K., and Momou, T.: "Caspase-12 processing and fragment translocation into nuclei of tunicamycin-treated cells"Cell Death Differ. 9. 1108-1114 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouroku, Y., Fujita, E., Jimbo, A., Kikuchi, T., Yamagata, T., Momoi, M..Y., Kominami, E., Kuida, K., Sakamaki, K., Yonehara, S., and Momoi, T.: "Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation"Human Mol. Genet. 11. 1505-1515 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita, E., Egashira, J., Urase, K., Kuida, K., Momoi, T.: "Caspase-9 processing via feedback amplification loop in vivo"Cell Death and Differentiation. 8. 335-344 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi, K., Kamiya, K., Urase, K., Suga, M., Takizawa, T., Mori, H., Yoshikawa, Y., Ichimura, K., Kuida, K., Momoi, T.: "Caspase-3-deficiency induces hyperplasia of supporting ceils and degeneration of sensory cells resulting in the hearing loss"Brain Res. 894. 359-367 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouroku Y, Fujita E, Urase K, Tsuru T, Setsuie R, Kikuchi T, Yagi Y, Momoi MY, Momoi T: "Caspases that are activated during generation of nuclear polyglutamine aggregates are necessary for DNA fragmentation but not sufficient for cell death"J Neurosci Res. 62. 547-556 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita E, Urase K, Egashira J, Miho Y, Isahara K, Uchiyama Y, Isoai A, Kumagai H, Kuida K, Motoyama N, Momoi T: "Detection of caspase-9 activation in the cell death of the Bcl-x-deficient mouse embryo nervous system by cleavage sites-directed antisera"Brain Res Dev Brain Res. 122. 135-147 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kouroku Y, Fujita E, Jimbo A, Mukasa T, Tsuru T, Momoi MY, Momoi T: "Localization of active form of caspase-8 in mouse L929 cells induced by TNF treatment and polyglutamine aggregates"Biochem Biophys Res Commun. 270. 972-977 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita E, Soyama A, Kawabata M, Momoi T: "BMP-4 and retinoic acid synergistically induce activation of caspase-9 and cause apoptosis of P19 embryonal carcinoma cells cultured as a monolayer"Cell Death Differ. 6. 1109-1116 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Momoi T., Fujita, E., Urase, K.: "Region-specific caspase-3-dependent programmed cell death in the developing forebrain"Neuroreport. 14. 111-115 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jimbo, A., Fujila, B., Kouroku, Y., Ohnishi, J., Inohara, N., Kuida, K., Sakainaki, K., Yonehara.S., Momoi, T.: "ER stress induces caspase-8 activation stimulating the cytochrome c release and caspase-9 activation"Exp. Cell. Res.. 283. 156-166 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitanaka C, Kato K, Ijiri R, Sakurada K, Tomiyama A, Noguchi K, Nagashima Y, Nakagawara A, Momoi T, Toyoda Y, Kigasawa H, Nishi T, Shirouzu M, Yokovama S, Tanaka Y, Kuchino Y.: "Increased ras expression and caspase independent neuroblastoma cell death : possible mechanism of spontaneous neuroblastoma regression"J. Nail. Cancer Inst.. 94. 358-368 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamoto Y, Kaneko S, Fan Ii, Mornoi T, Tsutsui H, Nakanishi K, Kobayashi K, Suda T.: "Prevention of Hepatocellular Carcinoma Development Associated with Chronic Hepatitis by Anti-Fas Ligand Antibody Therapy"Exp. Med.. 196. 1105-1111 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujita, E., Kouroku, Y., Jimbo, A., Maruyaina, K., Moinoi, T.: "Caspase-12 processing and fragment translocation into nuclei of tunicamycin-treated cells"Cell Death Differ.. 9. 1108-1114 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kouroku, Y., Fujita, E., Jiznbo, A., Kikuchi, T., Yainagata, T., Mornoi, MY, Korninarni E., Kuida, K., Sakamaki, K., Yonehara.S., Mornoi.T.: "Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation"Hum. Mol. Genet.. 11. 1505-1515 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujita E et al.: "Caspase-9 processing via feedback amplification loop in vivo."Cell Death and Differentiation.. 8. 335-344 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inada H et al.: "Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD."Cell Biol.. 155. 415-426 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitanaka C et al.: "Increased ras expression and caspase-independent neuroblastoma cell death : possible mechanism of spontaneous neuroblastoma regression."J Natl Cancer Inst.. 94. 358-368 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shigemura N et al.: "Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar"Histochem J.. 33. 253-258 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yaginuma H et al.: "Caspase activity is involved in, but is dispensable for, early motoneuron death in the chick embryo cervical spinal cord."Mol Cell Neurosci.. 18. 168-182 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hisahara S et al.: "Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination."J Exp Med.. 193. 111-122 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita,E. et al.: "Caspase-9 processing via feedback amplification loop in vivo."Cell Death and Differentiation. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hisahara,S. et al.: "Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination."J.Exp.Med.. 193. 111-122 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zheng,TS. et al.: "Deficiency of caspase-9 or caspase-3 induces the compensation of caspase."Nature Medicine. 6. 2141-2147 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujita,E. et al.: "Activation of caspase-9 in the nervous systems of Bcl-xL deficient mice embryos."Dev.Brain Res.. 122. 135-147 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanaka,M. et al.: "In situ detection of activated caspase-3 apoptotic granule neurons in the developing cerebellum in slice culture and in vivo."Dev.Brain Res.. 121. 223-228 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikezoe,K. et al.: "A novel congenital myopathy with apoptotic changes."Acta.Neurology. 47. 531-536 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miho Y., et al.: "bFGF inhibits the activation of caspase-3 and apoptosis of P19 embryonal carcinoma cells during neuronal differentiation"Cell Death Differ.. 6. 463-470 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mukasa T. et al.: "Activation of caspase-3 apoptotic pathways in skeletal muscle fibers in laminin alpha2-deficient mice"Biochem Biophys Res Commun.. 260. 139-142 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujita, E. et al.: "Akt phosphorylation site found in human caspase-9 is absent in mouse caspase-9"Biochem Biophys Res Commun.. 264. 550-555 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujita, E. et al.: "BMP-4 and retinoic acid synergistically induce activation of caspase-9 and cause apoptosis of P19 embryonal carcinoma cells cultured as a monolayer"Cell Death Differ.. 6. 1109-1116 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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