• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2002 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 2000 – 2002
Keywordsinositol phosphate / apoptosis / pleckstrin homology domain / calcium ion / HeLa cells / phospholipase C
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

  • Research Products

    (10 results)

All Other

All Publications (10 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

URL: 

Published: 2004-04-14  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi