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Studies on mammalian Ca^<2+>-dependent phospholipase A_2s

Research Project

Project/Area Number 09470507
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionShowa University

Principal Investigator

KUDO Ichiro  School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30134612)

Co-Investigator(Kenkyū-buntansha) KUWATA Hiroshi  School of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (80286864)
SHIMBARA Satoko  School of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (60266161)
NAKATANI Yoshihito  School of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (80266163)
ATSUMI Gen-ichi  School of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (70276608)
MURAKAMI Mokoto  School of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (60276607)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1998: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1997: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsPhospholipase A_2 / Cyclooxygenase / Prostagrandin / Arachidonic acid / Phospholipid / ホスホリパーゼA2 / アラキドン酸代謝 / cPLA_2 / sPLA_2 / COX / アポトーシス
Research Abstract

Phospholipase A_2 (PLA_2) represents a growing family of enzymes that catalyze the hydrolysis of phospholipids at the sn-2 position, liberating free fatty acids inducing arachidonic acid (AA), a precursor of bioactive eicosanoids, and lysophospholipids. PLA_2 has been implicated in diverse cellular responses, such as signal transduction, host defense, blood coagulation, cigestion, and membrane remodeling. Accorcing to an updated classification, PLA2_2 can be subdivided into several groups based upon their stnictures and enzymatic characteristics, inducing Ca^2-dependent cytosolic (cPLA_2) and secretory (sPLA_2) PLA_2 isozymes and Ca^<2+>-independent PLA_2 (iPLA_2). In the present study, the functional coupling of several clstinct PLA_2s and two cyclooxygenase (COX) isoforms during immediate and delayed PG-biosynthetic responses was examined cPIA_2, sPLA_2-IIA and sPLA_2-V were " signaling PLA-_2s" that promoted AA release from cells after stimulation with ionophore or bradykinin, which … More evoked the immediate response, and IL-1, which induced the delayed response. AA released by these signaling PLA_2s was converted to PGE_2 by both COXs during the immediate response and pretbminantly by COX-2 during the dulayed response. iPLA,, which plays a crucial role in "phospholipid remodeling', failed to couple with COX-2 during the delayed response, whereas it was linked to ionophore-induced immeciate PGE_2 generation via COX-l in preference to COX-2. sPLA_2-X induced fatty acid release in a manner similar to iPIA_2 rather than other sPLA2s. Extracellular sPLA_2s-IIA and -V.but neither intracellular cPLA_2 nor iPLA_2, augmented PGE_2 synthesis by neighboring COX-expressing cells, implying that these sPLA_2s play a particular role as paracrine amplifiers of the PG-biosynthetic response signal from one cell to another. After cell activation, signaling PLA_2s were localized around the nucleus where both COX isozymes were present. cPLA_2 bound to vimentin, a perinuclear intermeiziate filament protein, in Ca^<2+>-dependent manner and translocated from the cytosol to perinuclear membrane. sPLA_2-IIA bound a GPI-anchored heparan sulfate proteoglycan glypican, which &livered sPLA_2-IIA into caveolae and perinuclear sites and augmented sPLA_2-IIA-meciated A.A release and PGE_2 generation. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Murakami, M.et al.: "Functional coupling between various phospholipase A_2s and cyclooxygenases in immediate and delayed prostanoid biosynthetic pathways." J.Biol.Chem.274. 3103-3115 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada, K.et al.: "Induction of COX-2 by sPLA_2s in NGF-stimulated rat serosal mast cells is facilitated by interaction with fibroblasts and mediated by a mechamism independent of their enzymatic functions." J.Immunol.161. 5008-5015 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murakami, M.et al.: "The functions of five distinct mammalian PLA_2s in regulating arachidonic acid release : type IIA and type VsPLA_2s are functionally redundant and act in concert with cPLA_2." J.Biol.Chem.273. 14411-14423 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsumi, G.et al.: "Fas-induced arachidonic acid release is mediated by Ca^<2+>-independent phospholipase A_2 but not cytosolic phospholipase A_2, which undergoes proteolytic inactivation." J.Biol.Chem.273. 13870-13877 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuwata, H.et al.: "cPLA_2 is required for cytokine-induced expression of type IIA sPLA_2 that mediates optimal COX-2-dependent delayed PGE_2 generation in rat 3Y1 fibroblasts." J.Biol.Chem.273. 1733-1740 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naraba, H.et al.: "Segregated coupling of phospholipass A_2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages." J.Immunol.160. 2974-2982 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murakami, M., Kambe, T., Shimbara, S., and Kudo, I.: "Functional coupling between various phospholipase A_2s and cyclooxygenases in immdeiate and delayed prostanoid biosynthetic pathways." J.Biol.Chem.274. 3103-3115 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tada, K., Murakami, M., Kambe, T., and Kudo, I.: "Induction of cyclooxygenase-2 by secretory phospholipase A_2s in nerve growth factor-stimulted rat serosal mast cells is facilitated by interaction with fibroblasts and mediated by a mechamism independent of their enzymatic functions." J.Immunol.161. 5008-5015 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murakami, M., Shimbara, S., Kambe, T., Kuwata, H., Winstead, M.V., Tischfield, J.A., and Kudo, I.: "The functions of five distinct mammalian phospholipase A_2s in regulating arachidonic acid release : type IIA and type V secretory phospholipase A_2s are functionally redundant and act in concert with cytosolic phospholipase A_2s." J.Biol.Chem.273. 14411-14423 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsumi, G., Tajima, M., Hadano, A., Nakatani, Y., Murakami, M., and Kudo, I.: "Fas-induced arachidonic acid release is mediated by Ca^<2+>-independent phospholipase A_2 but not cytosolic phospholipase A_2 which undergoes proteolytic inactivation." Biol.Chem.273. 13870-13877 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kuwata, H., Nakatani, Y., Murakami, M., and Kudo, I.: "Cytosolic phospholipase A_2 is required for cytokine-induced expression of type IIA secretory phospholipase A_2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in rat 3Y1 fibroblasts." J.Biol.Chem.273. 1733-1740 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naraba, H., Murakami, M., Matsumoto, H., Shimbara, S., Ueno, A., Kudo, I., and Oh-ishi, S.: "Segregated coupling of phospholipases A_2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages." J.Immunol.160. 2974-2982 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Murakami,M.et al.: "Functional coupling between various phospholipase A_2s and cyclooxygenases in immediate and delayed prostanoid biosynthetic pathways." J.Biol.Chem.274. 3103-3115 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tada,K.et al.: "Induction of COX-2 by sPLA_2s in NGF-stimulated rat serosal mast cells is facilitated by interaction with fibroblasts and mediated by a mechamism independent of their enzymatic functions." J.Immunol.161. 5008-5015 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Murakami,M.et al.: "The functions of five distinct mammalian PLA_2s in regulating arachidonic acid release: type IIA and type V sPLA_2s are functionally redundant and act in concert with cPLA_2." J.Biol.Chem.273. 14411-14423 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Atsumi,G.et al.: "Fas-induced arachidonic acid release is mediated by Ca^<2+>-independent phospholipase A_2 but not cytosolic phospholipase A_2,which undergoes proteolytic inactivation." J.Biol.Chem.273. 13870-13877 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kuwata,H.et al.: "cPLA_2 is required for cytokine-induced expression of type IIA sPLA_2 that mediates optimal COX-2-dependent delayed PGE_2 generation in rat 3Y1 fibroblasts." J.Biol.Chem.273. 1733-1740 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naraba,H.et al.: "Segregated coupling of phospholipases A_2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages." J.Immunol.160. 2974-2982 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Kuwata et al.: "Cytosolic phospholipase A_2 is required for cytokine-induced expression of type IIA phospholipase A_2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in rat 3Y1 fibroblasts" Journal of Biological Chemistry. 273. 1733-1740 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Murakami et al.: "Detection of secretory phospholipase A_2 released but not identical to type II isozyme in C57BL/6J mouse-derived mast cells" FEBS Letter. 413. 249-254 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Murakami et al.: "Prostaglandin E_2 amplifies cytosolic phospholipase A_2 and cyclooxygenase-2-dependent delayed prostaglandin E_2 generation in mouse osteoblast cells : Enhancement by secretory phospholipaase A_2" Journal of Biological Chemistry. 272. 19891-19897 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] G.Atsumi et al.: "Perturbed membrane of cells undergoing apoptosis is susceptible to type II secretory phospholipase A_2 to liberate arachidonic acid" Biochimica Biophysica Acta. 1349. 43-54 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Murakami et al.: "Cyclooxygenase-2-dependent delayed prostaglandin D_2 generation is initiated by nerve growth factor in rat peritoneal mast cells : Its augmentation by extracellular type II secretory phospholipase A_2" Journal of Immunology. 159. 439-446 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Q.-R.Chen et al.: "Activation of cytosolic phospholipase A_2 by platelet-derived growth factor is essential for cyclooxygenase-2-dependent prostaglandin E_2 synthesis in mouse osteoblasts cultured with interleukin-1" Journal of Biological Chemistry. 272. 5952-5958 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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