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STUDY OF APOPTOSIS IN VITRO CELL-FREE SYSTEM

Research Project

Project/Area Number 08044281
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionOsaka University Medical School

Principal Investigator

TSUJIMOTO Yoshihide  Osaka University Medical School, Professor, 医学部, 教授 (70132735)

Co-Investigator(Kenkyū-buntansha) LAZEBNIK Yuri  Cold Spring Harbor Laboratories, Senior lnvestigator, 研究員
SHIMIZU Shigeomi  Osaka University Medical School, Assistant Professor, 医学部, 助手 (70271020)
KAMADA Shinji  Osaka University Medical School, Assistant Professor, 医学部, 助手 (20243214)
EGUCHI Yutaka  Osaka University Medical School, Assocate Professor, 医学部, 助教授 (20243206)
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsapoptosis / mitochondria / ICE / bcl-2 / Bc1-2
Research Abstract

Apoptosis is an important suicide program involved in a variety of biological phenomena including morphogenesis and maintenance of tissue homeostasis. Apoptosis is an important theme not only in biology but also in medical field because dysregulation of apoptosis leads to various diseases such as cancer and Alzheimer's disease. However, the molecular basis of apoptosis is still largely unknown. We have been studying ICE family proteases with apoptosis-driving activity and bcl-2 family with anti-apoptotic activity. For detailed study of the function of known genes involved in apoptosis and also for identification of new apoptosis-related genes, in vitro apoptosis system would be extremely useful. Although one system originally developed by Y.Lazebnik has been widely used, we have developed a new system which resembles much better in vivo apoptosis than Lazebnik's system.
Recently we have shown that mitochondrial dysfunction through membrane potential loss which is inhibited by Bcl-2, plays an important role in apoptosis. To analyze the biochemical basis of Bcl-2 anti-apoptotic function, we have established a system with isolated mitochondria in which Bcl-2 functions to prevent membrane potential loss.
These systems would be very useful for study of molecular basis of apoptosis, and likely provide new insights into control of diseases developing though deregulation of apoptosis.

Report

(2 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] H.Iwahashi: "Cytokine-induced apoptotic cell death in a mouse pancreatic beta cell line: inhibition by bcl-2" Diabetologia. 39. 530-536 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J-i.Hasegawa: "Involvement of CPP32/Yama (-like) proteases in Fas-mediated apoptosis." Cancer Research. 56. 1713-1718 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Shimizu: "Induction of apoptosis as well as necrosis by hopoxia and predominant prevention of apoptosis by bcl-2 and bcl-xL" Cancer Research. 56. 2161-2166 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Shimizu: "Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: Possible common steps in apoptosis" Oncogene. 12. 2045-2050 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Shimizu: "Bcl-2 expression prevents activation of the ICE protease cascade." Oncogene. 12. 2251-2257 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Shimizu: "Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of." Oncogene. 13. 21-29 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Iwahashi, H., Hanafusa, T., Eguchi, Y., Nakajima, H., Miyagawa, J., Itoh, N., Tomita, K., Namba, M., Kuwajima, M., Noguchi, T., Tsujimoto, Y.and Matsuzawa, Y.: "Cytokine-induced apoptotic cell death in a mouse pancreatic beta cell line : inhibition by bcl-2." Diabetologia. 39. 530-536 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hasegawa, J.I., Kameda, S., Kamiike, W., Shimizu, S., Imazu, T., Matsuda, H.and Tsujimoto, Y.: "Involvement of CPP32/Yama (-like) proteases in Fas-mediated apoptosis." Cencer Res.56. 1713-1718 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimizu, S., Eguchi, Y., Kamiike, W., Itoh, Y., Hasegawa, J.I., Yamabe, K., Ohtsuki, Y., Matsuda, H.and Tsujimoto, Y.: "Induction of apoptosis as well as necrosis by hypoxia and predominant prevention of apoptosis by bcl-2 and bcl-xL." Cancer Res.56. 2161-2166 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimuzu, S., Eguchi, Y., Kamiike, W., Waguri, S., Uchiyama, Y., Matsuda, H.and Tsujimoto, Y.: "Prevention of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors Possible common steps in apoptosis and necrosis." Oncogene. 12. 2045-2050 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimizu, S., Eguxhi, Y., Kamiike, W., Matsuda, H.and Tsujimoto, Y.: "Bcl-2 expression prevents activation of the ICE protease cascade." Oncogene. 12. 2251-2257 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimizu, S., Eguchi, Y., Kamiike, W., Waguri, S., Uchiyama, Y., Matsuda, H.and Tsujimoto, Y.: "Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors." Oncogene. 13. 21-29 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuda, Y., Kusano, H.and Tsujimoto, Y.: "Chromosomal assignment of the bcl-2-related genes, bcl-x and bax, in the mouse and rat." Cytogenet.Cell Genet.74. 107-110 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimizu, S., Eguchi, Y., Kamiike, W., Akao, Y., Kosaka, H., Hasegawa, J.i.Matsuda, H.and Tsujimoto, Y.: "Involvement of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes." Am.J.Physiol.271. G949-G958 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takahashi, T., Honda, H., Hirai, H.and Tsujimoto, Y.: "Overexpression of Bcl-xL prevents bacterial superantigen-induced apoptosis of thymocytes in vitro." Cell Death & Differ. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanabe, H., Eguchi, Y., Kamada, S., Martinou, J.-C/and Tsujimoto, Y.: "Susceptibility of cerebellar granule neurons derived from bcl-2-deficient and transgenic mice to cell death." Eur.J.Neurosci.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yasuhara, N., Eguchi, Y., Tachibana, T., Imamoto, N., Yoneda, Y.and Tsujimoto, Y.: "Essential role of active nuclear transport in apoptosis." Genes to Cells. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Iwahashi: "Cytokine-induced apoptotic cell death in a mouse pancreatic beta cell line: inhibition by bc1-2" Diabetologia. 39. 530-536 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.I.Hasegawa: "Involvement of CPP32/Yama(-like)proteases in Fas-mediated apoptosis." Cancer Research. 56. 1713-1718 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shimizu: "Induction of apoptosis as well as necrosis by hopoxia and predominant prevention of apoptosis by bc1-2 and bc1-xL." Cancer.Research. 56. 2161-2166 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shimizu: "Retardation of chemical hypoxia-induced necrotic cell death by Bc1-2 and ICE inhibitors:Possible common steps in apoptosis and necrosis." Oncogene. 12. 2045-2050 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shimizu: "Bc1-2 expression prevents activation of the ICE protease cascade." Oncogene. 12. 2251-2257 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shimizu: "Bc1-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of deathinduced by respiratory chain inlibitors." Oncogene. 13. 21-29 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Matsuda: "Chromosomal assignment of the bc1-2-related genes,bc1-x and bax,in the mouse and rat." Cytogenet.Call Genet.74. 107-110 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shimizu: "Involvement of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes." Ame.J.Physiol.271. G949-G958 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Takahashi: "Overexpression of Bc1-xL prevents bacterial superantigen-induced apoptosis of thymocytes in vitro." Cell Death and Differ.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Tanabe: "Susceptibility of cerebellar granule neurons derived from bc1-2-deficient and transgenic mice to cell death." Eur.J.Neurosci.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Yasuhara: "Essential role of active nuclear transport in apoptosis." Genes to Cells. (in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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