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Analysis of oncogenesis in relation to the roles for a novel inositol 1,4,5-trisphosphate binding protein

Research Project

Project/Area Number 12671948
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKyushu University

Principal Investigator

MATSUKI Nori-aki  Faculty of Dental Science, Ass. Professor, 大学院・歯学研究院, 助手 (90284520)

Co-Investigator(Kenkyū-buntansha) KANEMATSU Takashi  Faculty of Dental Science, Aso. Professor, 大学院・歯学研究院, 助教授 (10264053)
HIRATA Masato  Faculty of Dental Science, Professor, 大学院・歯学研究院, 教授 (60136471)
OHISHI Masamichi  Faculty of Dental Science, Professor, 大学院・歯学研究院, 教授 (70037505)
MATSUDA Miho  Faculty of Dental Science, Ass. Professor, 大学院・歯学研究院, 助手 (40291520)
竹内 弘  九州大学, 歯学研究院, 助手 (70304813)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsinositol phosphate / apoptosis / pleckstrin homology domain / calcium ion / HeLa cells / phospholipase C / 細胞生存 / NFκB / カスパーゼ / イノシトール1, 4, 5-三リン酸 / イノシトールリン脂質 / イノシトール三リン酸 / 蛋白質脱リン酸化酵素(PP1) / 口腔腫瘍 / PHドメイン / カルシウムシグナリング
Research Abstract

PRIP-1 was originally identified as an inositol 1,4,5-trisphosphate [Ins(1,4,5)P_3] binding protein similar to phospholipase C (PLC)-δ1, but lacking any phospholipase activity. In this study we analyzed the effects of the pleckstrin homology domain (PH domain) of PRIP-1 on the Ins(1,4,5)P_3-mediated Ca^<2+> signaling using permeabilized and intact HeLa cells, and found that PRIP-1PH domain had an inhibitory effect on Ca^<2+> signaling. PRIP-1PH domain inhibited the Ins(1,4,5)P_3-mediated Ca^<2+> release from permeabilized cells in a dose-dependent manner. When fura-2 loaded HeLa cells transfected with PRIP-1PH domain were stimulated with ATP, it was found that the agonist-induced increase in free Ca^<2+> concentration, observed in control cells, was inhibited in transfected cells. This inhibition was not accompanied by the reduced production of Ins(1,4,5)P_3. These results suggest that PRIP-1 has a potential to inhibit Ins(1,4,5)P_3-mediated Ca^<2+> signaling.
It has been reported that … More inositol hexakisphosphate (InsP_6, phytic acid), a natural product, has an anticancer role. In the present study, we investigated the mechanism by which InsP_6 acts as an anticancer agent. Treatment of HeLa cells with InsP_6 at 1 mM induced apoptosis, as assessed by counting the cell number, and by Hoechst and TUNEL staining. This is probably mediated by intracellular InsP_6 itself and/or the dephosphorylated forms of metabolized InsP_6, because incubation of HeLa cells with [^3H]InsP_6 produces dephosphorylated forms such as InsP_4 and InsP_5. Induction of apoptosis by InsP_6 was examined in two ways: inhibition of cell survival signaling and direct induction of apoptosis. As well as inhibiting the cell survival Akt-NF_κB pathway, InsP_6 itself caused mitochondrial permeabilization, followed by cytochrome c release, which later caused activation of the apoptotic machinery, caspase 9, 3 and poly (ADP-ribose) polymerase. These results revealed that extracellularly-applied InsP_6 directly activates the apoptotic machinery as well as inhibits the cell survival signaling, probably by the intracellular delivery followed by a dephosphorylation. Less

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Matsuki, N.et al.: "Antibodies against the PH domain of phospholipase C-δ1 inhibit Ins(1,4,5) P_3-mediated Ca^<2+> release from the endoplasmic reticulum"Biochemical and Biophysical Research Communications. 260. 42-47 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi, H.et al.: "Inhibition of calcium signalling by p130, PLC-related catalytically inactive protein : critical role of the p130PH domain"The Biochemical Journal. 349. 357-368 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuki, N.et al.: "Role of the pleckstrin homology domain of PLC-related catalytically inactive protein, p130 in Ca^<2+> signaling"Current Topics in Biochemical Research. 4. 117-127 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sandra, F.et al.: "TNF inhibited the apoptosis by activation of Akt serine/threonine kinase in the human head and neck squamous cell carcinoma"Cellular Signalling. 14. 771-778 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sandra, F.et al.: "Inositol hexakisphosphate blocks tumor cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NF_KB-mediated cell survival"Carcinogenesis. 23. 2031-2041 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuki, N., Tateishi, K., Takeuchi, H., Yagisawa, H., Kanematsu, T., Oishi, M. and Hirata, M.: "Antibodies against the PH domain of phospholipase C-δ1 inhibit Ins(1,4,5)P_3-mediated Ca^<2+> release from the endoplasmic reticulum"Biochem. Biophys. Res. Commun.. 260. 42-47 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi, H., Oike, M., Paterson, H.F., Allen, V., Kanematsu, T., Ito, Y., Erneux, C., Katan, M. and Hirata, M.: "Inhibition of calcium signaling by p130, PLC-related catalytically inactive protein: critical role of the p130PH domain"Biochem. J.. 349. 357-368 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuki, N., Takeuchi, H., Oike, M., Liao, J., Sandra, F., Ohishi, M., Kanematsu, T. and Hirata, M.: "Role of the pleckstrin homology domain of PLC-related catalytically inactive protein, p130 in Ca^<2+> signaling"Curr. Top. Biochem. Res.. 4. 117-127 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sandra, F., Matsuki, N., Takeuchi H., Ikebe, M., Kanematsu, T., Ohishi, M. and Hirata, M.: "TNF inhibited the apoptosis by activation of Akt serine/threonine kinase in the human head and neck squamous cell carcinoma"Cell. Signal.. 14. 771-778 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sandra, F., Matsuda, M., Yoshida, H. and Hirata, M.: "Inositol hexakisphosphate blocks tumor cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NF_κB-mediated cell survival pathway"Carcinogenesis. 23. 2031-2041 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sandra, F. et al.: "Inositol hexakisphosphate blocks tumor cell growth by activating apoptotic machinery as well as by inhibiting the Akt/ NFκB-mediated cell survival"Carcinogenesis. 23. 2031-2041 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sandra, F. et al.: "TNF inhibited the apoptosis by activation of Akt serine/threonine kinase in the human head and neck squamous cell carcinoma"Cellular Signalling. 14. 771-778 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuki, N. et al.: "Role of the pleckstrin homology domain of PLC-related catalytically inactive protein, p130 in Ca^<2+> signaling"Current Topics in Biochemical Research. 4. 117-127 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kishigami, A. et al.: "Inositot-1,4, 5-frisphosphate-binding proteins controlling the phototransduction cascade of invertebrate visual cells"J. Exp. Biol.. 204. 487-493 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshimura, K. et al.: "Interaction of p130 with, and consequent inhibition of, the catalytic subunit of protein phosphatase 1α"J. Biol. Chem.. 276. 17908-17913 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hidaka, K. et al.: "Involvement of the phosphoinositide 3-kinase/protein kinase B signaling pathway in insulin/IGE-I-induced chondrogenesis of the mouse embryonal carcinoma-derived cell line ATDC5"Int. J. Biochem. Cell Biol.. 33. 1094-1103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sandra, F. et al.: "TNF inhibited the apoptosis by activation of Akt serine/threonine kinase in the human head and neck squamous cell carcinoma"Cell. Signal.. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanematsu, T. et al.: "Role of the PLC-related, catalytically inactive protein p130 in GABA_A receptor function"EMBO J. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuki, N. et al.: "Role of the pleckstrin homology domain of PLC-related catalytically inactive protein, p130 in Ca^<2+> signaling"Curr. Top. Biochem. Res.. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi,H. et al.: "Inhibition of Ca2+ signalling by p130, a phospholipase-C-related catalytically inactive protein : critical role of the p130 pleckstrin homology domain."Biochemical Journal. 349. 357-368 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanematsu,T. et al.: "Domain organization of p130, PLC-related catalytically inactive protein,and structural basis for the lack of enzyme activity."European Journal of Biochemistry. 267. 2731-2737 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hermosura,M.C. et al: "InsP4 facilitates store-operated calcium influx by inhibition of InsP3 5-phosphatase."Nature. 408. 735-740 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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