• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Classification of human hypercholesterolemia by using somatic cell mutants with altered response to low density lipoprotein.

Research Project

Project/Area Number 62870012
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionMedical College of Oita

Principal Investigator

KUWANO Michihiko  Medical College of Oita, Department of Biochemistry Professor, 医学部, 教授 (80037431)

Co-Investigator(Kenkyū-buntansha) KOHNO Kimitoshi  Medical College of Oita, Department of Biochemistry Assistant Professor, 医学部, 助教授 (00153479)
TAKAKI Ryosaburo  Medical College of Oita, Professor, 医学部, 教授 (90038620)
ONO Mayumi  Medical College of Oita, Department of Biochemistry Assistant, 医学部, 助手 (80128347)
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥11,000,000 (Direct Cost: ¥11,000,000)
Keywordslow density lipoprotein / low density lipoprotein receptor / int gene / hypercholesterolemia / metabolic defects of cholesterol / defective O-glycosylation / somatic cell mutants / genetic-biochemistry / O-糖鎖不全 / 高コレステロール血症 / 低比重リポ蛋白(LDL) / LDLレセプター変異 / 細胞融合 / ゴルジ領域 / レセプター糖鎖修飾
Research Abstract

Familial hypercholesterolemia (FH) are caused by naturally occurring mutation of the low density lipoprotein (LDL) receptor. The repetoire of the naturally occurring mutation is limited. We have developed somatic cell mutants in culture with altered response to LDL, and experimentally induced mutations were successfully introduced into the LDL receptor. Our LDL receptor mutants showed following properties : 1. High cholesterol metabolism and low LDL binding. 2. Maturation of LDL receptor is defective and molecular size of the matured receptor is 5,000 smaller than the wild type. 3. Defective 0-linked sugar chains of LDL receptor. 4.0-linked sugar chains are also defective in the human LDL receptor cDNA-transfected mutants. 5. The defective receptor mutation was expressed recessively and the int gene was mutated in our mutants. 6. Collaboration study with Cummings and Merkle suggested that the dysfunction of LDL receptor was caused by loss of 0-linked sugar chains in LDL-binding or its neighboring domain. 7. The int mutation was supposed to involve in altered Golgi function.
Our study strongly propose that 0-linked sugar chains are indispensable to normal function of LDL receptor. Further study is in progress whether int mutation may cause hypercholesterolemia in human and also isolation of the int gene should be done.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Seguchi Tadashi: "The dysfunctional LDL receptor in a monensin-resistant mutant of Chinese hamster ovary cells lacks selected O-linked oligosaccharide." Journal of Biological Chemistry.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kuwano Michihiko: "Somatic cell mutants of low density lipoprotein receptor" Cell Structure and Function. 14. 501-507 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shite Satoshi: "A new class mutation of low density lipoprotein receptor with altered carbohydrate chains." Journal of Biological Chemistry. 263. 19286-19289 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshimura Akihiko: "Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chineses hamster ovary cells." Journal of Biological Chemistry. 262. 13299-13301 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshida Takashi: "Altered function and structure of low density lipoprotein receptor in compactin(ML236B)-resisitant mutants of Chinese hamter cell." Biochimica Biophysica Acta. 921. 575-586 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tomita Kichinobu: "Chinese hamster ovary cell mutant with defective down-regulation of low density lipoprotein receptors." Jouranl of Biological Chemistry. 263. 19286-19289 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kuwano Michihiko: "Drug resistance in mammalian cell Vol.II Anticancer and other drugs" CRC Press,R.S.Gupta(ed.), 20 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 桑野信彦: "Pharma Medica:「動脈硬化ー最近の話題」" メディカルレビュ-社, 10 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Seguchi Tadashi: "The dysfunctional LDL receptor in a monensin-resistant mutant of Chinese hamster ovary cells lacks selected O-linked oligosaccharide." Journal of Biological Chemistry.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kuwano Michihiko: "Somatic cell mutants of low density lipoprotein receptor." Cell Structure and Function 14:501-507 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shite Satoshi: "A new class mutation of low density lipoprotein receptor with altered carbohydrate chains." Journal of Biological Chemistry 263:19286-19289 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshimura Akihiko: "Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chinese hamster ovary cells." Journal of Biological Chemistry 262:13299-13301 (1987).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshida Takashi: "Altered function and structure of low density lipoprotein receptor in compactin (ML236B)-resistant mutants of Chinese hamster cell." Biochimica Biophysica Acta 921:575-586 (1987).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tomita Kichinobu: "Chinese hamster ovary cell mutant with defective down-regulation of low density lipoprotein receptors." Journal of Biological Chemistry 263:19286-19289 (1987).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kuwano Michihiko: "Resistance to tunicamycin, compactin, amphotericin B and monensin." Drug Resistance in Mammalian Cell Vol.II Anticancer and other drugs (CRC Press, R.S.Gupta ed.)(1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Seguchi Tadashi: "The dysfunctional LDL receptor in a monensin-resistant mutant of Chinese hamster ovary cells lacks selected O-linked oligosaccharide." Journal of Biological Chemistry.

    • Related Report
      1989 Annual Research Report
  • [Publications] Kuwano Michihiko: "Somatic cell mutants of low density lipoprotein receptor." Cell Structure and Function. 14. 501-507 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Shite Satoshi: "A new class mutation of low density lipoprotein receptor with altered carbohydrate chains." Journal of Biological Chemistry. 263. 19286-19289 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yoshimura Akihiko: "Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chinese hamster ovary cells." Jornal of Biological Chemistry. 262. 13299-13301 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yoshida Takashi: "Altered function and structure of low density lipoprotein receptor in compactin(ML236B)-resistant mutants of Chinese hamster cell." Biochimica Biophysica Acta. 921. 575-586 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tomita Kichinobu: "Chinese hamster ovary cell mutant with defective down-regulation of low density lipoprotein receptors." Jornal of Biological Chemistry. 263. 19286-19289 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kuwano Michihiko: "Drug resistance in mammalian cell Vol.II Anticancer and other drugs" CRC Press,R.S.Gupta(ed.), 20 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 桑野信彦: "Pharma Madica:「動脈硬化-最近の話題」" メディカルレビュ-社, 10 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kichinobu Tomita: Journal of Biological Chemistry. 262. 1398-1404 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Takashi Yoshida: Biochimica et Biophysica Acta. 921. 575-586 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Akihiko Yoshimura: Journal of Biological Chemistry. 262. 13299-13308 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Akihiko Yoshimura: Journal of Biological Chemistry. 263. 11935-11942 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Satoshi Shite: Journal of Biological Chemistry. 263. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tadashi Seguchi: Journal of Cellular Physiology. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Michihiko Kuwano: "Resistance to tunicamycin,compactin,amphotericin B and monensin." Drug Resistance in Mammalian Cell ed.by R.S.Gupta.CRC Press,New York, (1988)

    • Related Report
      1988 Annual Research Report

URL: 

Published: 1987-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi