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The moleular biological investigation of the role of PAF in the progressive renal disease

Research Project

Project/Area Number 11671029
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionUniversity of Tokyo

Principal Investigator

NAKAO Akihide  University of Tokyo Department of Nephrology and Endocrinology, lecturer assistant prof., 医学部・附属病院, 講師 (10159056)

Co-Investigator(Kenkyū-buntansha) NOIRI Eise  University of Tokyo Department of Nephrology and Endocrinology, lecturer assistant prof., 医学部・附属病院, 助手 (00301820)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsprogressive renal disease / cellular infiltration / chemotaxis / LTB_4 / LTA4 hydrolase / ischemic reperfusion injury / LTB_4 / LTA_4 hydrolase / 好中球 / マクロファージ / 走行性
Research Abstract

Leukotriene B4 (LTB4), like PAF, is a kind of lipid mediator whose actions include the degranulations of polymorphonuclear leukocytes, the chemotaxis of valuable cells, and the adhesions of neutrophiles to vascular endothelial cells. Their biological effects are mediated through its specific receptor. Since the progression of renal disease has been reported to be reduced by the maneuvers such as inhibitions of infiltration of macrophage or neutrophiles, we investigated the role of LTB4 in the renal disease.
Firstly, we examined the distribution of leukotriene A4 hydrolase which catalyze the final step of the synthesis of LTB4, using RT-PCR, western blotting, and immunohistochemistry. The enzyme was shown to be localized ubiquitously in the kidney by the methods mentioned above. Indeed, glomeruli as well as tubules could synthesize LTB4 under the stimulation of arachidonic acid and calcium ionophore (Kidney Int 1999). It was also confirmed that the expression of this enzyme was also upregulated by the increase of the pressure stimulation by angiotensin II in the view of northern blotting, western blotting, and the enzyme activities (FEBS lett). Following the cloning of human LTB4 receptor, we cloned rat LTB4 receptor (Biochem Biophys Res Commun 1999). Finally, we investigated the role of LTB4 in the reperfusion injury of rat kidneys, a model of acute renal failure. It was shown that LTB4 receptor engineered CHO cells migrated into tubular and interstitial cells, and that the treatment with the LTB4 receptor antagonist mitigated the infiltration of inflammatory cells and ameliorated renal functions. These results suggested the important role of LTB4 in the reperfusion injury (Proc Natl Acad Sci USA 2000).

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Nakao A 他: "Ubiquitans localization of leukotriene A4 hydrolase inratnephron"Kidney Int.. 55. 100-108 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toda A 他: "Cloning and characterization of rat leukotrrene B4 recepton"Biochem Biophys Res Commun. 262. 806-812 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaka N 他: "Increased leukotriene A4 hydrolase empression in the heart of angizfension-II induced hypertensive rat"FEBS Lett. 463. 155-159 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noin E 他: "An inrive apprach Showing the chemotaotic actinty of leukofriene B4 in acute renal ischemic-reperfusion injury."Proc Natl Acad Sci USA. 97. 823-828 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toda A, Yokomizo T, Masuda K, Nakao A, Izumi T, Shimizu T.: "Cloning and characterization of rat leukotriene B(4) receptor."Biochem Biophys Res Commun.. 262(3). 806-12 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakao A, Watanabe T, Ohishi N, Toda A, Asano K, Taniguchi S, Nosaka K, Noiri E, Suzuki T, Sakai T, Kurokawa K, Shimizu T, Kimura S.: "Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron."Kidney Int.. 55(1). 100-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaka N, Nakao A, Ohishi N, Suzuki M, Aizawa T, Taguchi J, Nagai R, Shimizu T, Ohno M.: "Increased leukotriene A(4) hydrolase expression in the heart of angiotensin II-induced hypertensive rat."FEBS Lett.. 463(1-2). 155-9 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noiri E, Yokomizo T, Nakao A, Izumi T, Fujita T, Kimura S, Shimizu T.: "An in vivo approach showing the chemotactic activity of leukotriene B(4) in acute renal ischemic-reperfusion injury."Proc Natl Acad Sci USA.. 97(2). 823-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakao A 他: "Ubiguitoas localization of leukotriene A_4 hydrolase in rat nephron"Kidney Int.. 55(1). 100-108 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toda A 他: "Cloning and characterization of rat leukotriene B_4 receptor"Biochem Biophys Res Commun. 262(3). 806-812 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishizaka N 他: "Increased leukotriene A_4 hydrolase expression in the heart of angioteasin II-induced hypertensive rat"FEBS lett. 463(1-2). 155-159 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noiri E 他: "An in vivo approach showing the chemotactic activity of leukotriene B_4 in acute renal ischemic-reperfasion injury"Proc Natl Acad Sci USA. 97(2). 823-828 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noiri E et al.: "An in vivo approach showing the chemotactic activity of leukotrien B(4) in acute ***mic-rgenfusion in jury"Proc Natl Acad Sci USA. 97(2). 823-828 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Isizaka N et al.: "Increased leukotrien hydrolase expression in the heart of angiotensin II-induced hypertensive rat"FEBS Lett. 463(1-2). 155-159 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toda A et al.: "Cloning and characterization of rat leukotrien B(4) receptor"Biochem Biophys Res Commun. 262(3). 806-812 (199)

    • Related Report
      1999 Annual Research Report
  • [Publications] Noiri E et al.: "MTHER gene polymoplism as exacerbation factor on diabetic hephroporhy in type 2 diabetes"Diabetes. Care. 23(2). 260-260 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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