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Molecular mechanism of free radical-induced apoptosis

Research Project

Project/Area Number 10045069
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

WAKABAYASHI Takashi  School of Mrdicine, Nagoya University, Professor, 医学部, 教授 (00079998)

Co-Investigator(Kenkyū-buntansha) NIKI Ichiro  School of Medicine, Nagoya University, Assoc.Professor, 医学部, 助教授 (10262908)
YOSHIDA Shonen  School of Medicine, Nagoya University, Professor, 医学部, 教授 (70090420)
HAYAKAWA Tetsuo  School of Medicine, Nagoya University, Professor, 医学部, 教授 (80022838)
JERZY Krechn  グダニスク医科系大学, 教授
ZDZISLAW Wai  グダニスク医科系大学, 教授
MICHAL Wozni  グダニスク医科系大学, 助教授
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsmegamitochondria / free radicals / scavengers / apoptosis / TEMPO derivatives / culture cells / 4-OH-TEMPO / 微小管 / taxol / nocodazole / acetylated α-tubulin / coenzymeQ_<10> / ミトコンドリア形態制御遺伝子 / mmml / mdm10 / スカベンジャー
Research Abstract

1. Establishment of the experimental model for the megamitochondria (MG) formation using culture cells.
2. Mechanism of the MG formation :
Free radicals are involved as the mechanism common to the MG formation induced by various pathologic conditions.
3. Pathophysiological meaning of the free radical-induced MG formation :
Cell in the presence of MG become apoptotic with time. MG decrease the rate of oxygen consumption thus decreasing the generation of oxygen radicals. This contributes to the suppression of the increase in the intracellular level of free radicals. If such effect do not efficiently work, cells become apoptotic.
4. Suppression of the MG formation by scavengers of free radicals : MG induced both in vivo and in vitro by various chemicals were successfully suppressed by α-tocopherol, CoQ_<10>, or 4-OH-TEMPO most effectively by 4-OH-TEMPO.
5. Synthesis of TEMPO derivatives :
4-octanoyl-and 4-lauroyl-TEMPO, among newly synthesized 6 TEMPO derivatives, have been found much more effective than 4-OH-TEMPO in suppressing the MG formation.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Wakabayashi,T.,Karbowski,M.: "Structural changes of mitochondria related to apoptosis"Biological Signals and Receptors Special issue on mitochondria (Review Article). 10. 26-56 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Karbowshi,M.,Spodonik,J.,Teranishi,M.,Wakabayashi,T. et al.: "Opposite effects of microtubule-stabilizing and microtubule-destabilizing drugs on biogenesis of mitochondria in mammalian cells"Journal of Cell Science. 114. 281-291 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi,T.,Spodnik,J: "Structural changes of mitochondria during free radical-induced apoptosis"Folia Morphologica (Review Article). 59. 61-75 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Teranishi,M.,Spodonik,J.,Karbowshi,M.,Kurono,C.,Wakabayashi,T. et al.: "Swelling of free radical-induced megamitochondria causes apoptosis"Exp.Mol.Pathol.. 68. 104-123 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi,T.,Teranishi,M.,Karbowski,M. et.al.: "Functional aspects of megamitochondria isolated from hydrazine-and ethanol-treated rat livers"Pathology International. 50. 20-33 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Teranishi,M.,Karbowski,M. et al.: "Two types of the enlargement of mitochondria related to apoptosis : simple swelling and the formation of megamitochondria."Journal of Electron Microscopy. 48. 637-651 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Popinigis,J.,Ziolkowski,W. et al.: "Altered function of permeability transition in liver mitochondria from three months propanol-treated rat."Polish Journal of Environmental Studies. 8. 359-362 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi,T.: "Structural changes of mitochondria related to apoptosis : swelling and megamitochondria formation"Acta Biochimica Polonica. 46. 223-237 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Teranishi,M.,Karbowski,M. et al.: "Effects of Coenzyme Q10 on changes in the membrane potential and rate of generation of reactive oxygen species in hydrazine- and chloramphenicol-treated rat liver mitochondria."Archives of Biochem.Biophysics. 366. 157-167 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Karbowski,M.,Kurono,C., et al.: "Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria."Biochim.Biophys.Acta. 144. 25-40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Karbowski,M.,Kurono,C., et al.: "Free radical-induced megamitochonria formation and apoptosis"Free Rad.Biol.Med.. 26. 396-409 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuhashi,T.,Karbowski,M., et al.: "Complete suppression of ethanol-induced formation of megamitochondria by 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4-OH-TEMPO)"Free Rad.Biol.Med.. 24. 139-147 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Popinigis,J.,Antosiewicz,J., et al.: "Dysfunction of the outer mitochondrial membrane seems to be compensated inside the cell by the formation of megamitochondria."Polish J.Environmental Studies. 7. 371-372 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi, T., Kaerbowski, .M.: "Structural changes of mitochondria related to apoptosis"Biological Signals and Receptors Secial issue on mitochondria (Review Article). 10. 26-56 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Karbowski, M., Spodonik, J., Teranishi, M., Wakabayashi, T.et al.: "Opposite effects of microtubule-stabilizing and microtubule-destabilizing drugs on biogenesis of mitochondria in mammalian cells"Journal of Cell Science. 114. 281-291 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi, T., Spodnik, J.: "Strucutural changes of mitochondria during free radical-induced apoptosis"Folia Morphologica (Review Article). 59. 61-75 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Teranishi, M., Spodonik, J., Karbowski, M., Kurono, C., Wakabayashi, T.et al.: "Swelling of free radical-induced megamitochondria causes apoptosis"Exp.Mol.Pathol.. 68. 104-123 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi, T., Teranishi, M., Karbowski, M.et al.: "Functional aspects of megamitochondria isolated from hydrazine-and ethanol-treated rat livers"Pathology Internntional. 50. 20-33 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Teranishi, M., Karbowski, M.et al.: "Two types of the enlargement of mitochondria related to apoptosis : simple swelling and the formation of megamitochondria"Journal of Electron Microscopy. 48. 637-651 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Popinigis, J., Ziolkowski, W.et al.: "Altered function of permeability transition in liver mitochondria from three months propanol-treated rat"Polish Journal of Environmental Studies. 8. 359-362 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi, T.: "Structural changes of mitochondria related to apoptosis : swelling and megamitochondria formation"Acta Biochimica Polonica. 46. 223-237 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Teranishi, M., Karbowski, M.et al.: "Effects of Coenzyme Q10 on changes in the membrane potential and rate of generation of reactive oxygen species in hydrazine- and chloramphenicoltreated rat liver mitochondria"Archives of Biochem.Biophysics. 366. 157-167 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Karbowski, M., Kurono, C.et al.: "Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria"Biochim.Biophys.Acta. 144. 25-40 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Karbowski, M., Kurono, C.et al.: "Free radical-induced megamitochondria formation and apoptosis"Free Rad.Biol.Med. 26. 396-409 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuhashi, T., Karbowski, M.et al.: "Complete suppression of ethanol-induced formation of megamitochondria by 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-1-oxyl (4-OH-TEMPO)"Free Rad.Biol.Med. 24. 139-147 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Popinigis, J., Antosiewicz, J.et al.: "Dysfunction of the outer mitochondrial membrane seems to be compensated inside the cell by the formation of megamitochondria"Polish J.Environmental Studies. 7. 371-372 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wakabayashi,T.,Karbowski,M.: "Structural changes of mitochondria related to apoptosis"Biological Signals and Receptors Special issue on mitochondria (Review Article). 10. 26-56 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Karbowski,M.,Spodonik,J.,Teranishi,M.,Wakabayashi,T. et al.: "Opposite effects of microtubule-stabilizing and microtubule-destabilizing drugs on biogenesis of mitochondria in mammalian cells"Journal of Cell Science. 114. 281-291 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wakabayashi,T.,Spodnik,J: "Structural changes of mitochondria during free radical-induced apoptosis"Folia Morphologica (Review Article). 59. 61-75 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Teranishi,M.,Spodonik,J.,Karbowski,M.,Kurono,C.,Wakabayashi,T. et al.: "Swelling of free radical-induced megamitochondria causes apoptosis"Exp.Mol.Pathol.. 68. 104-123 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wakabayashi,T.,Teranishi,M.,Karbowski,M.Wakabayashi,T. et al.: "Functional aspects of megamitochondria isolated from hydrazine-and ethanol-treated rat livers"Pathology International. 50. 20-33 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wakabayashi,T.,Teranishi,M.et al.: "Functional aspects of megamitochondria isolated from hydrazine- and ethanol-treated rat livers."Pathology International. 50. 20-33 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Teranishi,M.,Karbowski,M.et al.: "Two types of the enlargement of mitochondria related to apoptosis: simple swelling and the formation of megamitochondria."Journal of Electron Microscopy. 48. 637-651 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Popinigis J.,Ziolkowski W.et al.: "Altered function of permeability transition in liver mitochondria from three months propanol-treated rat."Polish Journal of Environmental Studies. 8. 359-362 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Wakabayashi,T.: "Structural changes of mitochondria related to apoptosis: Swelling and megamitochondria formation."Acta Biochimica Polonica. 46. 223-237 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Teranishi,M.,Kawbowski,M.et al.: "Effects of Coenzyme Q10 on changes in the membrane potential and rate of generation of reactive oxygen species in hydrazine- and chloramphenicol-treated rat liver mitochondria."Archives of Biochem.Biophysics. 366. 157-167 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Karbowski,M.,Kurono,C.,et al.: "Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria." Biochim.Biophys.Acta. 144. 25-40 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Karbowski,M.,Kurono,C.,et al.: "Free radical-induced megamitochondria formation and apoptosis." Free Rad.Biol.Med.26. 396-409 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kamimoto,T.,Nagai,Y.,et al.: "Dymple,a novel dynamin-like high molecular weight GTPase lacking a proline-rich carboxyl-terminal domain in mammalian cells." J.Biol.Chem.273. 1044-105* (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsuhashi,T.,Karbowski,M.,et al.: "Complete suppression of ethanol-induced formation of megamitochondria by 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl(4-OH-TEMPO)." Free Rad.Biol.Med.24. 139-147 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Popinigis,J.,Antosiewicz,J.,et al.: "Dysfunction of the outer mitochondrial membrane seems to be compensated inside the cell by the formation of megamitochondria." Polish J.Environmental Studies. 7. 371-372 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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