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Signal transduction of lung surfactant synthesis, transport, and secretion in alveolar type II cell

Research Project

Project/Area Number 10670566
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKanazawa Medical University

Principal Investigator

OSANAI Kazuhiro  Kanazawa Med.Univ.Resp.Med.Assistant Professor, 医学部, 講師 (70221158)

Co-Investigator(Kenkyū-buntansha) TOGA Hirohisa  Kanazawa Med.Univ.Resp.Med.Associate Professor, 医学部, 助教授 (90142554)
TAKAHASHI Keiji  Kanazawa Med.Univ.Resp.Med.Professor, 医学部, 教授 (50004685)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordslung surfactant / alveolar type II cell / intracellular transport / lamellar body / brefeldin A
Research Abstract

Lung surfactant, a mixture of lipids and apoproteins, is synthesized in alveolar type II cells and is essential substance for maintaining lung homeostasis. This research project has revealed followings. (1) Phosphatidylcholine, a major lipidcomponent of lung surfactant, is synthesized in endoplasmic reticulum, transported to and stored in lamellar bodies via the Golgi-independent pathway. In contrast, surfactant protein A, one of the four apoproteins, is synthesized in endoplasmic reticulum, transported to the Golgi and is glycosylated, and is constitutively secreted out of the cells. The secreted protein is endocytosed into alveolar type II cells and transported to lamellar bodies. (2) The research also identified and partially characterized an intracellular molecule of an approximately 110 kD molecular weight on a gel filtration chromatography, which induces surfactant exocytosis. (3) ADP-ribosylation of adenylate cyclase-associated heterotrimeic G protein by cholera toxin unexpectedly but strongly inhibits lung surfactant secretion. These results indicate that the postulated pathway of lung surfactant so far is wrong, and have brought new aspects of lung surfactant biology. (4) Furthermore, we have investigated effects of lung deflation and several agents on alveolar water clearance. Taken together, these findings will lead to better understanding of pathogenesis of acute respiratory failure and a novel therapeutic strategy.
These results were published in medical journals, presented in medical meetings, and submitted to medical books. Especially, these papers published in American medical journals counted totally 11.295 of Impact Factor (Journal Citation Report, ISI).

Report

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

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kazuhiro Osanai, et al.: "Expression and localization of a novel Rab small G protein(Rab38)in the rat lung"Am J Pathol. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai, et al.: "Pulmonary surfactant phosphatidylcholine transport bypasses the brefeldin A sensitive compartment of alveolar type II cells"Biochim Biophys Acta. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai, et al.: "Trafficking of newly synthesized surfactant proteinA in isolated rat alveolar type II cells."Am J Respir Cell Mol Biol. 19. 929-935 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 長内和弘,他: "Permeabilized rat alveolar type II cellsからのフォスファチジルコリンの分泌"日本界面医学会雑誌. 31. 26-32 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutomu Sakuma, et al.: "Lung deflation impairs alveolar epithelial fluid transport irischemic rabbit and rat lungs."Transplantation. 69. 1785-1793 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutomu Sakuma, et al.: "Denopamine, a beta1-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs."J Appl Physiol. 90. 10-16 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai, et al.: "Expression and localization of a novel Rab small G protein (Rab38) in the rat lung"Am J Pathol. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai, et al.: "Pulmonary surfactant phosphatidylcholine transport bypasses the brefeldin A sensitive compartment of alveolar type II cells"Biochim Biophys Acta. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai, et al.: "Trafficking of newly synthesized surfactant protein A in isolated rat alveolar type II cells."Am J Respir Cell Mol Biol. 19. 929-935 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai, et al.: "Phosphatidylcholine secretion from permeabilized rat alveolar type II cells."J Jpn Med Soc Biol Interface. 31. 26-32 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutomu Sakuma, et al.: "Lung deflation impairs alveolar epithelial fluid transport inischemic rabbit and rat lungs."Transplantation. 69. 1785-1793 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutomu Sakuma, et al.: "Denopamine, a beta1-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs."J Appl Physiol. 90. 10-16 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutomu Sakuma, et al.: "Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs."Jpn J Pharmacol. 85. 161-166 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kazuhiro Osanai et al: "Trafficking of newly synthesized surfactant apoprotein A in isolated rat alveolar type II cells"Am J Respir Cell Mol Biol. vol.19(6). 929-935 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuhiro Osanai et al: "Trafficking of newly synthesized surfactant apoprotein A in alveolar type II cells" American Journal of Respiratory Cell and Molecular Biology. vol.19(6). 929-935 (1998)

    • Related Report
      1998 Annual Research Report

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

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