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Role of cholesterol crystallization-promoting protein in the pathogenesis of cholesterol gallstone.

Research Project

Project/Area Number 05670445
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionUniversity of Tsukuba

Principal Investigator

TANAKA Naomi  Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (60111530)

Co-Investigator(Kenkyū-buntansha) ABEO Masato  Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (20261802)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsgallstone / cholesterol / alpha_1-acid glycoprotein / nucleation / biliary protein / immunoglobulins / crystal growth / 結晶成長 / α_1-アシドグリコプロテイン / 胆石症 / コレステロール胆石症 / nucleation time / α_1-acid glycoprotein
Research Abstract

Rapid cholesterol crystallization in bile is the critical event leading to cholesterol gallstone formation. Several glycoprotein promoters (immunoglobulins, phospholipase C,aminopeptidase N) of cholesterol crystallization have recently been reported in bile with gallstones, which have received world-wide attention. We have successfully isolated a new promoter and identified it as alpha_1-acid glycoprotein. However, no study compared these promoters in vitro and their precise role in the pathogenesis of gallstones remains unknown. Therefore, we aimed in this study to clarify the role of these cholesterol crystallization-promoters in the pathogenesis of gallstones. Firstly, the cholesterol crystallization-promoting activity of these glycoproteins was compared in vitro. It was found that only alpha_1-acid glycoprotein and immunoglobulins exsert the promoting activity at their physiologic levels in bile. Secondly, the biliary levels of alpha_1-acid glycoprotein in various gallstone and non-gallstone patients were assayd by a newly established specific ELISA and compared with the cholesterol nucleation time in bile. This revealed that the alpha_1-acid glycoprotein level is not altered in biles with solitary cholesterol or pigment gallstones but it is specifically elevated in biles with multiple cholesterol gallstones and that its increase is associated with rapid nucleation time. The potent promoting activity in vitro as well as the specific increase in bile (in vivo) with multiple cholesterol gallstones suggest the critical role of the biliary alpha_1-acid glycoprotein in the formation of multiple cholesterol gallstones.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 安部井誠人: "ヒト胆汁中コレステロール結晶形成促進蛋白の解析(精製、同定、定量)とそのコレステロール胆石形成における意義" 薬理と治療. 23. S693-S698 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masato Abei: "Cholesterol crystallization-promoters in human bile:comparative protencies of immunoglobulins α_1-acid glycoprot,phospholipase C,and aminopeptidasell." Journal of Lipid Research. 34. 1141-1148 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masato Abei: "Identification of human biliary α_1-acid glycoprotein as a cholesterol crystallization promote" Gastroenterology. 106. 231-238 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 安部井誠人: "胆石の生成機序-コレステロール胆石" 肝胆膵. 27. 649-656 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 田中直見: "消化器診療プラクティス(4)胆嚢疾患" 文光堂, 245 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 安倍井 誠人: "ヒト 胆汁中コレステロール結晶形成促進蛋白の解析(精製同定、定量)とそのコレステロール胆石形成における意義" 薬理と治療. 23. S693-S698 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Abei Masato: "Cholesterol crystallization-promoters in human bile" Journal of Lipid Research. 34. 1141-1148 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Abei Masato: "Identification of human biliary α_1-acid glycoprotein as a cholesterol crystallization promoter" Gastroenterology. 106. 231-238 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 安倍井 誠人: "胆石の生成機序-コレステロール胆石" 肝胆膵. 27. 649-659 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 田中 直見: "消化器診療プラクティス(4)胆嚢疾患" 文光堂, (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 田中直見: "胆石の分類" 消化器診療プラクテイス 4.胆嚢症患-胆石症を中心に. 10-13 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 田中直見: "胆石症" 300症患診療マニュアル,中井利昭編,中外医学社. 172-173 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 田中直見: "胆汁酸" modern physician. 13. 1607-1609 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Abei Masato: "Isolation and characterization of a cholesterol crystallization promotor from human bile" Gastroenterology. 104. 539-548 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Abei Masato: "Cholesterol crystallization-promotors in human bile:Comparative promoting activities of immunoglobulins,α_1-acid glycoprotein,phospolipase,and aminopepidase" J Lipid Res. 34. 1141-1148 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Abei Masato: "Identification of human biliary α_1-acid glycoprotein as a cholesterol crystallization promotor" Gastroenterology. 106. 231-238 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 安部井誠人: "消化器内科診療プラクティス(4)胆嚢疾患 コレステロール胆石はどうしてできるか" 文光堂, 14-17 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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