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1995 Fiscal Year Final Research Report Summary

Isozymes of cyclooxygenase and lipoxygenase

Research Project

Project/Area Number 06454179
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionTokushima University

Principal Investigator

YAMAMOTO Shozo  Department of Biochemistry, University of Tokushima, School of Medicine Professor, 医学部, 教授 (50025607)

Co-Investigator(Kenkyū-buntansha) SUZUKI Hiroshi  Department of Biochemistry, University of Tokushima, School of Medicine Research, 医学部, 助手 (80253194)
HAYASHI Yoko  Department of Biochemistry, University of Tokushima, School of Medicine Research, 医学部, 助手 (60035441)
UEDA Natsuo  Department of Biochemistry, University of Tokushima, School of Medicine Associat, 医学部, 助教授 (20193807)
Project Period (FY) 1994 – 1995
KeywordsArachidonic acid / Prostaglandin / Anadamide / Lipoxygenase / 12-Lipoxygenase / Cyclooxygenase-1 / Cyclooxygenase-2 / Baculovirus
Research Abstract

Bioactive eicosanoids such as prostaglandins, thromboxanes and leukotrienes are produced from arachidonic acid which is the substrate of various lipoxygenases and cyclooxygenases. We studied the catalytic properties and the regulatory mechanism of gene expression of these enzymes with special reference to their isozymes.
1)Selective inhibitor of 5-lipoxygenase : An antioxidant YT-18 caused a lag phase prior to initiation of 5-lipoxygenase reaction. This effect was specific for 5-lipoxygenase.
2)Suicide inactivation of 12-lipoxygenase : Leukocyte 12-lipoxygenase is a typical suicide enzyme.The enzymeproduced 15-hydroperoxy acid as a minor product from arachidonic acid, which was further transformed to 14,15-epoxy acid by the same enzyme. Several lines of evidence suggested the inactivation of the enzyme which incorporated the 14,15-epoxy acid. Platelet 12-lipoxygenase produced little amount of 15-hydroperoxy acid and was scarcely suicide-inactivated.
3)Anandamide as substrate of leukocyte 12-lipoxygenase : Anandamide(arachidonylethanolamine)is an endogenous ligand of cannabinoid receptor. The compound was oxygenated by leukocyte 12-lipoxygenase, but was a poor substrate of platelet enzyme. The 12-oxygenated anandamide was biologically almost inactive.
Transcriptional regulation of 12-lipoxygenase gene : The promoter region of platelet 12-lipoxygenase gene was examined, and NFkB element(-539 to -530bp)was proposed to negatively regulate the transcription of the enzyme gene.
Induction of cyclooxygenase-1 : Human megakaryoblastic CMK cells were treated wtih TPA,which induced cyclooxygenase-1 enzyme.
Transcriptional regulation of cyclooxygenase-2 : When murine osteoblastic MC3T3-E1 cells were treated with TNFalpha, cyclooxygenase-2 was induced. Several lines of experimented findings suggested a regulatory role of NFkB and NF-IL6 in the transcription of cyclooxygenase-2.

  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] H.Suzuki: "Site-directed mutagenesis studies on the iron-binding domain and the determinant for the substrate oxygenation site of porcine leukocyte arachidonate 12-lipoxygenase" Biochim.Biophys.Acta. 1210. 308-316 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Hada: "Arachidonate 12-lipoxygenase of rat pineal glands : catalytic properties and primary structure deduced from its cDNA" Biochim.Biophys.Acta. 1211. 221-228 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takahashi: "Studies on the induction of cyclooxygenase isozymes by various prostaglandins in mouse osteoblastic cell line with reference to signal transduction pathways" Biochim.Biophys.Acta. 1212. 217-224 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.-L.Gu: "Evidence that a leukocyte type of 12-lipoxygenase is expressed and regulated by angiotensin II in human adrenal glomerulosa cells" Endocrinology. 134. 70-77 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.-W.Liu: "Induction of 12-lipoxygenase expression by epidermal growth factor is mediated by protein kinase C in A431 cells" J.Pharmacol.Exp.Ther.271. 567-573 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Kuhn: "Oxidative modification of human lipoproteins by lipoxygenases of different positional specificities" J.Lipid Res.35. 1749-1759 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Ueda: "Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide" J.Biol.Chem.270. 23823-23827 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Nakamura: "Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase inmouse blood cells" J.Histochem.Cytochem.43. 237-244 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Arakawa: "The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NFκB/Rel" FEBS Lett.363. 105-110 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Endo: "Induction of cyclooxygenase-2 is responsible for interleukin-1β-dependent prostaglandin E_2 synthesis by human lung fibroblasts" Am.J.Respir.Cell Mol.Biol.12. 358-365 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Ueda: "Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide,a cannabinoid receptor agonist" Biochim.Biophys.Acta. 1254. 127-134 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yamamoto: "Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in the tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells" J.Biol.Chem.270. 31315-31320 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Yamamoto and W.L.Smith (eds.): "Molecular Biology of the Arachidonate Cascade" Elsevier Science B.V., 380 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Suzuki: "Site-directed mutagenesis studies on the iron-binding domain and the determinant for the substrate oxygenation site of porcine leukocyte arachidonate 12-lipoxygenase" Biochim.Biophys.Acta.1210. 308-316 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Hada: "Arachidonate 12-lipoxygenase of rat pineal glands : catalytic properties and primary structure deduced from its cDNA" Biochim.Biophys.Acta. 1211. 221-228 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Takahasi: "Studies on the induction of cyclooxygenase isozymes by various prostaglandins in mouse osteoblastic cell line with reference to signal transduction pathways" Biochim.Biophys.Acta. 1212. 217-224 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.L.GU: "Evidence that a leukocyte type of12-lipoxygenase is expressed and regulated by angiotensin II in human adrenal glomerulosa cells" Endocrinology. 134. 70-77 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.W.LIU: "Induction of 12-lipoxygenase expression by epidermal growth factor is mediated by protein kinase C in A431 cells" J.Pharmacol.Exp.Ther.271. 567-573 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Kuhn: "Oxidative modification of human lipoproteins by lipoxygenases of different positional specificties" J.Lipid Res.35. 1749-1759 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Ueda: "Partial purfication and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide" J.Biol.Chem.270. 23823-23827 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Nakamura: "Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells" J.Histochem.Cytochem.43. 237-244 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Arakawa: "The transcriptional regulation of human arachidonate 12-lipoxygenase gene by NFkB/Rel" FEBS Lett.363. 105-110 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Endo: "Induction of cyclooxygenase-2 is responsible for interleukin-1beta-dependent prostaglandin E_2 synthesis by human lung fibroblasts" Am.J.Respir.Cell Mol.Biol.12. 358-365 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Ueda: "Lipoxygenase-catalyzed oxygenation of arachidonylethanolamide, a cannabinoid receptor agonist" Biochim.Biophys.Acta.1254. 127-134 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamamoto: "Transcriptional roles of nuclear factor kB and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells" J.Biol.Chem.270. 31315-31320 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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