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Mechanisms for tissue specific expression and cell growth of 12/15-lipoxygenase

Research Project

Project/Area Number 10670134
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionKanazawa University

Principal Investigator

YOSHIMOTO Tanihiro  School of Medicine, Kanazawa University Professor, 医学部, 教授 (60127876)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords12-Lipoxygenase / Athelosclerosis / Low density lipoprotein (LDL) / Oxidized LDL / Scavenger receptor / Macrophage / 低比重リボタンパク質 / スカベンジャ-受容体 / アラキドン酸 / リポキシゲナーゼ / cDNAクローニング
Research Abstract

Lipoxygenase (LOX) incorporates a molecular oxygen into a specific carbon atom of unsaturated fatty acids. There are 5-, 8-, 12- and 15-LOXs in mammalian tissues according to the oxygenation site of arachidonic acid. Based upon the primary structures deduced from their cDNAs and enzymological properties, they are principally classified into 5-LOX and 12/15-LOX subfamilies. The 5-LOX catalyzes the first step in the generation of leukotrienes which have potent biological activities in the immediate hypersensitivity and allergy. There are number of isoforms of 12/15-LOXs : leukocyte, platelet and epidermis. Although the 12/15-LOXs have been shown to play roles in several systems such as atherosclerosis and neurotransmission, their pathophysiological functions are still subjects of investigation and discussion.
There are a body of circumstantial evidences for a role of LOX in oxidative modification of low density lipoprotein (LDL). The aim of this study was to investigate the role of intrac … More ellular 12-LOX in the oxidative modification of LDL that leads to foam cell formation. We overexpressed 12-lipoxygenases in a macrophage-like cell line J774A.1 which originally did not show the detectable enzyme activity. When the 12-lipoxygenase-expressing cells were incubated with LDL in Dulbecco's modified Eagle medium at 37 ℃ for 12 h, LDL oxidation as determined by thiobarbituric acid reactive substance was markedly increased over the mock-transfected cells. Oxygenated products in the modified LDL were examined by high performance liquid chromatography before and after alkaline hydrolysis. Most of the oxygenated derivatives were of an esterified form, and the major product was identified to be 13S-hydroxyoctadeca-9Z, 11E-dienoic acid. These results clearly demonstrated that esterified fatty acids in LDL were oxygenated by the 12-lipoxygenases expressed in the J774A.1 cells. Furthermore, the oxidized LDL generated by intracellular 12-lipoxygenases was recognized by a scavenger receptor as assessed by macrophage degradation assay. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] T. Sakashita, et al.: "Essential involvement of 12-lipoxygenase in regiospecific and stereospecific oxidation of low density lipoprotein by macrophages"Eru. J. Biochem.. 265. 825-831 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Ozaki, et al.: "An anti-platelet agent, OPC-29030, inhibits translocation of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid production in human platelets"Br. J. Pharmacol.. 128. 1699-1704 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Takahashi, et al.: "12-Lipoxygenase overexpression in rodent NG108-15 cells enhances membrane excitability by inhibiting M-type K^+ channels"J. Physiol. (London). 521. 567-574 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Takahashi, et al.: "Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2"FEBS Lett.. 460. 145-148 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Kinoshita, et al.: "Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells"Biochem. Biophys. Acta.. 1438. 120-130 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Sakashita, et al.: "Essential involvement of 12-lipoxygenase in regiospecific and stereospecific oxidation of flow density lipoprotein by macrophages"Eur. J. Biochem.. 265. 825-831 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Ozeki, et al.: "An anti-platelet agent, OPC-29030, inhibits translocation of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid production in human platelets"Br. J. Pharmacol.. 128. 1699-1704 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Takahashi, et al.: "12-Lipoxygenase overexpression in rodent NG108-15 cells enhances membrane excitability by inhibiting M-type KィイD1+ィエD1 channels"J. Physiol. (London). 521. 567-574 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Takahashi, et al.: "Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2"FEBS Lett.. 460. 145-148 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Kinoshita, et al.: "Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells"Biochim. Biophys. Acta.. 1438. 120-130 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Sakashita, et al.: "Essential involvement of 12-lipoxygenase in regiospecific and stereospecific oxidation of low density lipoprotein by macrophages"Eur. J. Biochem.. 265. 825-831 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Ozeki, et al.: "An anti-platelet agent, OPC-29030, inhibits translocation of 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid production in human platelets"Br. J. Pharmacol.. 128. 1699-1704 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Takahashi, et al.: "12-Lipoxygenase overexpression in rodent NG108-15 cells enhances membrane excitability by inhibiting M-type K^+ channels"J. Physiol. (London). 521. 567-574 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y. Takahashi, et al.: "Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2"FEBS Lett.. 460. 145-148 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Kinoshita, et al.: "Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells"Biochim. Biophys. Acta.. 1438. 120-130 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroyuki Takamatsu, T.et al.: "Continuous antibody production by phytohemagglutinin-L-aggregated hybridoma cells" Journal of Immunological Methods.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Takahiro Kinoshita, T.et al.: "Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells" Biochimica et Biophysica Acta. (印刷中).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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