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Dissection of the molecular mechanism of the novel neurotrophin-like effects of secretory phospholipase A_2

Research Project

Project/Area Number 16580054
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied microbiology
Research InstitutionThe University of Tokyo

Principal Investigator

ARIOKA Manabu  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (20242159)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordssecretory phospholipase A_2 / neurotrophic factor / L-type Ca^<2+> channel / apoptosis / PC12 / cerebellar granule neuron / neurite outgrowth / Aspergillus oryzae / 神経突起伸張
Research Abstract

We previously demonstrated that secretory phospholipase A_2 (sPLA_2) and lysophosphatidylcholine (LPC) exhibit neurotrophin-like neuritogenic activity in the rat pheochromocytoma cell line PC12. Furthermore, sPLA_2 and LPC rescued cerebellar granule neurons from apoptotic cell death induced by deprivation of depolarizing stimulus. In the current study, we further analyzed the mechanism whereby sPLA_2 displays neurite-inducing activity. Exogenously-added mammalian group X sPLA_2 (sPLA_2-X), but not group IB and IIA sPLA_2s, induced neuritogenesis, which correlated with the ability of sPLA_2-X to liberate LPC into the culture media. In accordance, blocking the effect of LPC by supplementation of bovine serum albumin or phospholipase B attenuated neuritogenesis by sPLA_2 or LPC. Overproduction or suppression of G2A, a G protein-coupled receptor involved in LPC signaling, resulted in the enhancement or reduction of neuritogenesis induced by sPLA_2 treatment. These results indicate that neu … More ritogenic effect of sPLA_2 is mediated by generation of LPC and subsequent activation of G2A.
In contrast to mammalian sPLA_2s, much less is known for the physiological function of microbial sPLA_2. We cloned and characterized spaA and spaB encoding putative sPLA_2s from a filamentous fungus Aspergillus oryzae. PLA_2 activity assays showed that recombinant SpaA and SpaB had different enzymatic characteristics. Western blot and immunofluorescence analyzes demonstrated that, while SpaA was mainly secreted to culture medium, SpaB was associated with the intracellular structures reminiscent of the endoplasmic reticulum and/or lipid body. The expression of spaA was induced in response to carbon starvation, oxidative stress and conidiation, while spaB was constitutively expressed at very low steady level and upregulated in the cold-stressed condition. spaA- and spaB-overexpressing strains showed poor-conidiation phenotype which was remarkable in the latter. Although no morphological abnormalities were found in spaA, spaB, and spaA/spaB disruptants, we found that conidia of spaA disruptant and hyphae of spaB disruptant became sensitive to oxidative stress. These results suggest that fungal sPLA_2s play roles in defense system to oxidative stress. Less

Report

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

    (33 results)

All 2006 2005 2004

All Journal Article (33 results)

  • [Journal Article] Visualization of the endocytic pathway in the filamentous fungus Aspergillus oryzae using an EGFP-fused plasma membrane protein.2006

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

      Biochem. Biophys. Res. Commun. 340・3

      Pages: 784-791

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vacuolar membrane dynamics in the filamentous fungus Aspergillus oryzae.2006

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

      Eukaryot. Cell 5・2

      Pages: 411-421

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Visualization of the endocytic pathway in the filamentous fungus Aspergillus oryzae using an EGFP-fused plasma membrane protein.2006

    • Author(s)
      Higuchi, Y., Nakahama, T., Shoji, J.Y., Arioka, M., Kitamoto, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 340(3)

      Pages: 784-791

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vacuolar membrane dynamics in the filamentous fungus Aspergillus oryzae.2006

    • Author(s)
      Shoji, J.Y., Arioka, M., Kitamoto, K.
    • Journal Title

      Eukaryot.Cell 5(2)

      Pages: 411-421

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SspA, an outer membrane protein, is highly induced under salt-stressed conditions and is essential for growth under salt-stressed aerobic conditions in Rhodobacter sphaeroides f. sp. denitrificans.2005

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

      Appl. Microbiol. Biotechnol. 68・2

      Pages: 242-250

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of Aspergillus oryzae thiA promoter as a tool for molecular biological studies.2005

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

      FEMS Microbiol. Lett. 244・1

      Pages: 41-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neuronal expression and neuritogenic action of group X secreted phospholipase A_2.2005

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

      J. Biol. Chem. 280・24

      Pages: 23203-23214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel neurotrophic role of secretory phospholipases A_2 for cerebellar granule neurons.2005

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

      FEBS Lett. 579・12

      Pages: 2693-2701

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Secretory phospholipases A_2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor.2005

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

      J. Biol. Chem. 280・30

      Pages: 28044-28052

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Isolation and characterization of vacuolar protein sorting mutants from Aspergillus oryzae.2005

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

      Appl. Environ. Microbiol. 71・8

      Pages: 4856-4861

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 分泌型ホスホリパーゼA_2の神経栄養因子としての新規な作用2005

    • Author(s)
      有岡 学
    • Journal Title

      バイオサイエンスとインダストリー 63・5

      Pages: 297-302

    • NAID

      10015711811

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] SspA, an outer membrane protein, is highly induced under salt-stressed conditions and is essential for growth under salt-stressed aerobic conditions in Rhodobacter sphaeroides f.sp.denitrificans.2005

    • Author(s)
      Tsuzuki, M., Xu, X., Sato, S., Abo, M., Arioka, M., Nakajima, H., Kitamoto, K., Okubo, A.
    • Journal Title

      Appl.Microbiol.Biotechnol. 68(2)

      Pages: 242-250

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of Aspergillus oryzae thiA promoter as a tool for molecular biological studies.2005

    • Author(s)
      Shoji, J.Y., Maruyama, J., Arioka, M., Kitamoto, K.
    • Journal Title

      FEMS Microbiol.Lett. 244(1)

      Pages: 41-46

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neuronal expression and neuritogenic action of group X secreted phospholipase A_2.2005

    • Author(s)
      Masuda, S., Murakami, M., Takanezawa, Y., Aoki, J., Arai, H., Ishikawa, Y., Ishii, T., Arioka, M., Kudo, I.
    • Journal Title

      J.Biol.Chem. 280(24)

      Pages: 23203-23214

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel neurotrophic role of secretory phospholipases A_2 for cerebellar granule neurons.2005

    • Author(s)
      Arioka, M., Ikeno, Y., Cheon, S.-h., Nakashima, S., Kitamoto, K.
    • Journal Title

      FEBS Lett. 579(12)

      Pages: 2693-2701

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Secretory phospholipases A_2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor.2005

    • Author(s)
      Ikeno, Y., Konno, N., Cheon, S.-h., Bolchi, A., Ottonello, S., Kitamoto, K., Arioka, M.
    • Journal Title

      J.Biol.Chem. 280(30)

      Pages: 28044-28052

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Isolation and characterization of vacuolar protein sorting mutants from Aspergillus oryzae.2005

    • Author(s)
      Ohneda, M., Arioka, M., Kitamoto, K.
    • Journal Title

      Appl.Environ.Microbiol. 71(8)

      Pages: 4856-4861

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Novel neurotrophic effects of secretory phospholipase A_2.2005

    • Author(s)
      Arioka, M.
    • Journal Title

      Bioscience and Industry (review in Japanese) 63(5)

      Pages: 297-302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neuronal expression and neuritogenic action of group X secreted phospholipase A_22005

    • Author(s)
      Masuda et al.
    • Journal Title

      J.Biol.Chem. 280(24)

      Pages: 23203-23214

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel neurotrophic role of secretory phospholipases A_2 for cerebellar granule neurons2005

    • Author(s)
      Arioka et al.
    • Journal Title

      FEBS Lett. 579(12)

      Pages: 2693-2701

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Secretory phospholipases A_2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor2005

    • Author(s)
      Ikeno et al.
    • Journal Title

      J.Biol.Chem. 280(30)

      Pages: 28044-28052

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 分泌型ホスホリパーゼA_2の神経栄養因子としての新規な作用2005

    • Author(s)
      有岡 学
    • Journal Title

      バイオサイエンスとインダストリー 63(5)

      Pages: 297-302

    • NAID

      10015711811

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SspA an outer membrane protein, is highly induced under salt-stressed conditions and is essential for growth under salt-stressed aerobic conditions in Rhodobacter sphaeroides f.sp.denitrificans.2005

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

      Appl.Microbiol.Biotechnol. (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of Aspergillus oryzae thiA promoter as a tool for molecular biological studies.2005

    • Author(s)
      Shoji, J., et al.
    • Journal Title

      FEMS Microbiol.Lett. 244・1

      Pages: 41-46

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Isolation and characterization of vacuolar protein sorting mutants from Aspergillus oryzae.2005

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

      Appl.Environ.Microbiol. (発表予定)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dibasic amino acid residues at the carboxy-terminal end of kinase homology domain participate in the plasma membrane localization and function of phosphatidylinositol 5-kinase γ.2004

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

      Biochem. Biophys. Res. Commun. 319・2

      Pages: 456-463

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The catalytic activity, but not receptor binding, of sPLA_2s plays a critical role for neurite outgrowth induction in PC12 cells.2004

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

      Brain Res. 1015・1-2

      Pages: 207-211

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Development of a novel quadruple auxotrophic host transformation system by argB gene disruption using adeA gene and exploiting adenine auxotrophy in Aspergillus oryzae.2004

    • Author(s)
      Jin, F.J., et al.
    • Journal Title

      FEMS Microbiol. Lett. 239・1

      Pages: 79-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dibasic amino acid residues at the carboxy-terminal end of kinase homology domain participate in the plasma membrane localization and function of phosphatidylinositol 5-kinase γ.2004

    • Author(s)
      Arioka, M., Nakashima, S., Shibasaki, Y., Kitamoto, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 319(2)

      Pages: 456-463

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The catalytic activity, but not receptor binding, of sPIA_2s plays a critical role for neurite outgrowth induction in PC12 cells.2004

    • Author(s)
      Nakashima, S., Kitamoto, K., Arioka, M.
    • Journal Title

      Brain Res. 1015(1-2)

      Pages: 207-211

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of a novel quadruple auxotrophic host transformation system by argB gene disruption using adeA gene and exploiting adenine auxotrophy in Aspergillus oryzae.2004

    • Author(s)
      Jin, F.J., Maruyama, J., Juvvadi, P.R., Arioka, M., Kitamoto, K.
    • Journal Title

      FEMS Microbiol.Lett. 239(1)

      Pages: 79-85

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dibasic amino acid residues at the carboxy-terminal end of kinase homology domain participate in the plasma membrane localization and function of phosphatidylinositol 5-kinase γ.2004

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

      Biochem.Biophys.Res.Commun. 319・2

      Pages: 456-463

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of a novel quadruple auxotrophic host transformation system by argB gene disruption using adeA gene and exploiting adenine auxotrophy in Aspergillus oryzae.2004

    • Author(s)
      Jin, F.J., et al.
    • Journal Title

      FEMS Microbiol.Lett. 239・1

      Pages: 79-85

    • Related Report
      2004 Annual Research Report

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

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