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REGULATORY MECHANISM BY PHOSPHOLIPASE D IN OXIDANT-STRESS INDUCED SURVIVAL SIGNALING

Research Project

Project/Area Number 16390098
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionGIFU INTERNATIONAL INSTITUTE OF BIOTECHNOLOGY

Principal Investigator

NOZAWA Yoshinori  GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOL, PRESIDENT, 所長兼部長 (10021362)

Co-Investigator(Kenkyū-buntansha) AKAO Yukihiro  GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOL, CHIEF, 部長 (00222505)
BANNO Yoshiko  GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSPCIATE PROFESSOR, 大学院・医学系研究科, 助教授 (50116852)
OHGUCHI Kenji  GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOL, HEAD, 主任研究員 (80359257)
NAKAGAWA Yoshihito  GIFU INTERNATIONAL INSTITUTE OF BIOTECHNOL, RESEARCHER, 研究員 (60372108)
松本 健司  財団法人岐阜県国際バイオ研究所, 専門研究員 (60288701)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2005: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2004: ¥8,400,000 (Direct Cost: ¥8,400,000)
KeywordsSignal transduction / Oxidative stress / Lipids / Phospholipase D / H_2O_2 / Aktキナーゼ / Pyk2キナーゼ / 生存シグナリング
Research Abstract

We examined implication of phospholipase D (PLD) in oxidative stress. The role of PLD activation in hydrogen peroxide (H_20_2)-induced signal transduction and cellular responses are not completely understood. We present evidence that Ca^<2+> tyrosine kinase, Pyk2 requires PLD activation to mediate survival pathways in rat pheochromocytoma PC12 cells under oxidative stress. The H_20_2-induced phosphorylation of Pyk2 was suppressed by 1-butanol, an inhibitor of transphosphatidylation by PLD, and also by transfection of catalytically negative mouse PLD2K758R (PLD2KR). Furthermore, we found that PLD2 was associated with Pyk2 and Src, and that activation of PLD2 was required for H_20_2-enhanced association of Src with Pyk2 leading to full activation of Pyk2. H_20_2-induced phosphorylation of Akt and p70S6K was dependent on phosphatidylinositol 3-kinase (PI3K) activity and was abolished by 1-butanol but not t-butanol. Furthermore, the PI3K/Akt activation in response to H_20_2 was reduced by … More transfection of either PLD2KR or the dominant negative Pyk2DN. This study is the first demonstration that PLD2 activation is implicated in Src-dependent phosphorylation of Pyk2 by promoting the complex formation between Pyk2 and activated Src in PC12 cells exposed to H_20_2, thereby resulting in activation of the survival signaling pathway PI3K/Akt/p70S6K.
A human prostate cancer cell line PC3 is resistant to camptothecin (CPU). To elucidate the mechanism of this resistance, we have examined the involvement of sphingosine kinase (SPHK) and sphingosine 1-phosphate (S1P) receptor in CPT-resistant PC3 and -sensitive LNCaP cells. PC3 cells exhibited higher activity accompanied with higher expression levels of protein and mRNA of SPHK1, and also elevated expression of SiP receptors, S1P1 and S1P3, as compared with those of LNCaP cells. The treatment of PC3 cells with CPT was found to induce up-regulation of the SPHK1/S1P signaling by induction of both SPHK1 enzyme and S1PL1/S1P3 receptors. These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (32 results)

All 2006 2005 2004 Other

All Journal Article (30 results) Book (2 results)

  • [Journal Article] High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation.2006

    • Author(s)
      Akao, Y., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 342

      Pages: 1284-1290

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Localization of sphingosine kinase-1 in mouse sperm acrosomes.2005

    • Author(s)
      Mastumoto, K., et al.
    • Journal Title

      J. Histochem. Cytochem. 53

      Pages: 243-247

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Localization of sphingosine kinase-1 in mouse sperm acrosomes.2005

    • Author(s)
      Mastumoto, K., et al.
    • Journal Title

      J.Histochem.Cytochem 53

      Pages: 243-247

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Implication of phospholipase D2 in oxidant-induced phosphoinositide 3-kinase signaling via Pyk2 activation in PC12 cells2005

    • Author(s)
      Banno, Y., et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 16319-16324

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sphingosine kinase 1 is involved in dibutyryl cyclic AMP-induced granulocytic differentiation through the upregulation of extracellular signal-regulated kinase, but not p38 MAP kinase, in HL60 cells.2005

    • Author(s)
      Koda, M., et al.
    • Journal Title

      Biochim.Biophys.Acta 1733

      Pages: 101-110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Negative regulation of melanogenesis by phospholipase D1 through mTOR/p70 S6 kinase 1 signaling in mouse B16 melanoma cells.2005

    • Author(s)
      Ohguchi, K., et al.
    • Journal Title

      J.Cell.Physiol. 205

      Pages: 444-451

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcription factor Sp1 is the main regulator of NGF-induced sphingosine kinase 1 gene expression of the rat pheochromocytoma cell line, PC12.2005

    • Author(s)
      Sobue, S., et al.
    • Journal Title

      J.Neurochem. 95

      Pages: 940-949

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of platelet-derived growth factor-induced cell growth signaling by a short interfering RNA for EWS-F1i1 via down-regulation of phospholipase D2 in Ewing's sarcoma cells.2005

    • Author(s)
      Nozawa, S., et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 27544-27551

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Arf1-dependent PLD1 is localized to oleic acid-induced lipids droplets in NIH3T3 cells.2005

    • Author(s)
      Nakamura, N., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 335

      Pages: 117-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Implication of PLD2 in oxidant-induced PI3 Kinase signaling via Pyk2 activation in PC 12 cells : A survival response.2005

    • Author(s)
      Banno Y. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 16319-16324

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Localization of sphingosine kinase-1 in mouse sperm acrosomes2005

    • Author(s)
      Matsumoto, K., et al.
    • Journal Title

      J.Histochem.Cytochem 53

      Pages: 243-247

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Negative regulation of melanogenesis by phospholipase D1 through mTOR/p70 S6 kinase 1 signaling in mouse B16 melanoma cells2005

    • Author(s)
      Ohguchi, K. et al.
    • Journal Title

      J.Cell.Physiol. 205,

      Pages: 444-451

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sphingosine kinase 1 is involved in bdcAMP-induced HL60 differentiation through upreglation of ERK2005

    • Author(s)
      Koda, M., et al.
    • Journal Title

      Biochim.Biophys.Acta 1733

      Pages: 101-110

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transcription factor specificity protein 1 (Sp 1) is the main regulator of nerve growth factor-induced sphingosine kinase 1 gene expression of the rat pheochromocytoma cell line, PC12.2005

    • Author(s)
      Sobue, S. et al.
    • Journal Title

      J.Neurochem. 95

      Pages: 950-961

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of platelet-derived growth factor-induced cell growth signaling by a short interfering RNA for EWS-Fli1 via down-regulation of phospholipase D2 in Ewing's sarcoma cells2005

    • Author(s)
      Nozawa S. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 27544-27551

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of phospholipase D1 in melanogenesis of mouse B16 melanoma cell.2004

    • Author(s)
      Ohguchi, K., et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 3408-3412

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of phospholipase D prevents actinomycin D-induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells.2004

    • Author(s)
      Yamada, M., et al.
    • Journal Title

      Biochem. J. 378

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Compartmenttation of the mouse cerebellar cortex by sphingosine kinase.2004

    • Author(s)
      Terada, N., et al.
    • Journal Title

      J. Comp. Neurol. 469

      Pages: 119-127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of phosphatidylcholine hydrolysis by phospholipase C in prostaglandin F2a-induced 1,2-diacylglycerol formation in osteoblast-like MC3T3-E1 cells.2004

    • Author(s)
      Sakai, T., et al.
    • Journal Title

      J. Bone Mineral Met. 22

      Pages: 198-206

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biochemical and cell biological analyses of a mammalian septin complex.2004

    • Author(s)
      Nagata, K., et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 55895-5594

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of phospholipase D prevents actinomycin D-induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells2004

    • Author(s)
      Yamada, M., et al.
    • Journal Title

      Biochem.J. 378

      Pages: 1-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of phospholipase D1 in melanogenesis of mouse B16 melanoma cell.2004

    • Author(s)
      Ohguchi, K., et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 3408-3412

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of phosphatidylcholine hydrolysis by phospholipase C in prostaglandin F2a-induced 1,2-diacylglycerol formation in osteoblast-like MC3T3-E1 cells.2004

    • Author(s)
      Sakai, T., et al.
    • Journal Title

      J.Bone Mineral Met. 22

      Pages: 198-206

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biochemical and cell biological analyses of a mammalian septin complex.2004

    • Author(s)
      Nagata, K., et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 55895-55904

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Compartmentation of the mouse cerebellar cortex by sphingosine kinase.2004

    • Author(s)
      Terada, N., et al.
    • Journal Title

      J.Comp.Neurol. 469

      Pages: 119-127

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of phospholipase D prevents actinomycin D-induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells2004

    • Author(s)
      Yamada, M. et al.
    • Journal Title

      Biochem.J. 378

      Pages: 1-8

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of phospholipase D1 in melanogenesis of mouse B16 melanoma cell2004

    • Author(s)
      Ohguchi, K. et al.
    • Journal Title

      J.Blol.Chem. 279

      Pages: 3408-3412

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Biochemical and cell biological analyses of a mammalian septin complex2004

    • Author(s)
      Nagata, K. et al.
    • Journal Title

      J.Blol.Chem. 279

      Pages: 55895-55904

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Sphingosine kinase 1 is involved in dibutyryl cyclic AMP-induced granulocytic differentiation through up-regulation of extracellular signal-regulated kinase, but not p38 MAP kinase, in HL60 cells

    • Author(s)
      Koda, M. et al.
    • Journal Title

      Biochim.Biophys.Acta In press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Implication of phospholipase D2 in oxidant-induced phosphoinositide 3-kinase signaling via Pyk2 activation in PC12 cells

    • Author(s)
      Banno, Y. et al.
    • Journal Title

      J.Blol.Chem. In press

    • Related Report
      2004 Annual Research Report
  • [Book] 脂質代謝酵素(3) ホスホリパーゼC.生物薬科学実験講座72005

    • Author(s)
      坂野喜子, 野澤義則
    • Total Pages
      10
    • Publisher
      廣川書店,
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 生物薬科学実験講座"情報伝達物質II シグナル伝達系と細胞機能"2005

    • Author(s)
      坂野喜子, 野澤義則
    • Total Pages
      11
    • Publisher
      広川書店
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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