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HDL-apoAI gene expression and its kinetics in vivo

Research Project

Project/Area Number 04671503
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionFukuoka University

Principal Investigator

SAKU Keijiro  Fukuoka Univ.Hospital, Dept.of Internal Medicine, Lecturer, 附属病院・内科, 講師 (40183371)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Kyousuke  Dept.of Medicine, Saga College, Internal Medicine, Associate Professor, 医学部・内科, 助教授 (00117285)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Keywordshigh-density lipoprotein / apoprotein AI / turnover study / proapolipoprotein AI / rabbit / messenger RNA / varinat apoprotein AI
Research Abstract

The metabolic turnover of HDL-apo AI has been studied in order to know the mechanism of low and high plasma HDL levels.
1) We attempted here to determine the kinetic parameters (turnover) of HDL apo AI in normal Japanese White (control) rabbits, with or without cholesterol, probucol and pravastatin feeding. ^<125>l-labeled HDL was injected intraveneously and blood samples were taken periodically for 6 days. Kinetic parameters were calculated from the apo AI specific radioactivity decay curves. We found that the apo AI fractional catabolic rates (FCR) in rabbits fed pravastatin with Ch (group 1) were significantly less than those in rabbits fed pravastatin plus probucol with Ch (group 2) (0.546(〕SY.+-.〔)0.017 /day vs. 0.730(〕SY.+-.〔)0.126 /day, p<0.05), while the synthetic rates (SR) of apo AI was lower in group 2 than in group 1 (14.76(〕SY.+-.〔)1.71 mg/kg/day vs. 11.21(〕SY.+-.〔)2.38 mg/kg/day.respectively, p<0.1) . These data indicate that pravastatin and probucol have different effects … More on HDL-apo AI kinetics in a diet which includes cholesterol. The addition of pravastatin to probucol did not enhance HDL metabolism in this expermental models, but rather reduce the synthesis of Apo AI.Total RNA was isolated from rabbit intestine under various conditions as stated above. Compared to findings in control rabbits, probucol or pravastatin treated rabbits showed no changes in mRNA level of apo AI.
2) In vivo conversion of recombinant human proapoprotein AI (rh-Met-proapo AI) from E.coli to apo AI was also investigated in rabbits in vivo. It was found that the radioactivity of rh-Met-proapo AI migrated to more acidic isoproteins, the conversion was complete within 24 hours. Thus, a) the proteolytic cleavage of proapo AI is an extracellular event, b) the converting enzyme from rabbits is functional for human proapo AI processing, and c) the injection of rh-Met-proapo AI into rabbits facilities understanding of the early events of HDL biogenesis in rabbits.
3) In vivo kinetics of lipoprotein(a) [Lp(a)] were also investigated in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia, and in normolipidemic Japanese White rabbits (controls). The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355(〕SY.+-.〔)0.189 pools per day and 1.278(〕SY.+-.〔)0.397 pools per day, respectively) in the WHHL rabbits were significantly (p<0.005) smaller than those in the control rabbits (2-008(〕SY.+-.〔)0.083 pools per day and 2.855(〕SY.+-.〔)0.759 pools per day, respectively) . Our data storongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some other mechanisms.
4) We found six types of apo AI variants. They were radiolabeled and injected into rabbits as above. We found no peculiar pathway for apo AI variants compated to the kinetics of native apo Al(Al_3) . Less

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Saku,K.et al: "In vivo conversion of recombinant human proapolipoprotein AI(rh-Met-proapo AI) to apolipoprotein AI in rabbits." Biochimica et Biophysica Acta. 1167. 257-263 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirata,K.,Saku,K.et al: "Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus." Kidney International. 44. 1062-1072 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saku,K.et al: "Combined therapy with probucol and pravastatin in hypercholesterolemia." European Journal of Clinical Pharmacology. 44. 535-539 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bai,H.,Saku,K.et al: "Polymorphic site study at codon 347 of apolipoprotein A-IV in a Japanese population" Biochimica et Biophysica Acta. 1174. 279-281 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Liu,R.,Saku,K.et al: "In vivo kinetics of lipoprotein(a) in homozygous Watanabe heritable hyperlipidemic rabbits" European Journal of Clinical Investigation. 23. 561-565 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saku,K.et al: "In vitro conversion of recombinant human proapolipoprotein AI to apolipoprotein AI." Biochimica et Biophysica Acta. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saku, K.et al: "In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) to apolipoprotein AI in rabbits." Biochimica et Biophysica Acta. 1167. 257-263 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirata, K., Saku, K.et al: "Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/withoutdiabetes mellitus." Kidney International. 44. 1062-1074 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saku, K.et al: "Combined therapy with probucol and pravastatin in hypercholesterolemia." European Jounal of Clinical phamacology.44. 535-539 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bai, H., Saku, K.et al: "Polymorphic site study at codon 347 of apolipoprotein A-IV in a Japanese population." Biochimica et Biophysica Acta.1174. 279-281 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Liu, R., Saku, K.et al: "In vivo kinetics of lipoprotein(a) in homozygous Watanabe heritable hyperlipidemic rabbits." European Jounal of Clinical Investigation.23. 561-565 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saku, K.et al: "In vivo conversion of recombinant human proapolipoprotein AI to apolipoprotein AI." Biochimica et Biophysica Acta.1217. 29-30 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saku,K.et al: "In vivo conversion of recombinant human proapolipo-protein AT to apolipoprotein AT." Biochimica et Biophysica Acta. 1167. 257-263 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirata,K.,Saku K.et al: "Apolipoprotein(a) phenotypes and serum lipoprotein(a)levels in maintenance hemodialysis pationts." Kidney International. 44. 1062-1072 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saku,K.et al: "Combined therapy with probucol and pravastatin in hypercholesterolemia" European Journal of Clinical Pharmacology. 44. 535-539 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Bai,H.,Saku,K.et al: "Polymorphic site study at dodon 347 of apolipoprotein A-IV in a Japanese population." Biochimica et Biophysica Acta. 1174. 279-281 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Liu,R.,Saku,K.et al: "In vivo kinetics of lipoprotein(a)in homozygous Watanabe heritable hvperlipidemic rabbits." European Journal Clinical Investigation. 23. 561-565 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saku,K.et al: "In vitro conversion of recombinant human proapolipoprotein AI to apolipoprotein AT." Biochimica et Biophysica Acta. in press.(1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sasaki,N.,Saku,K.,et al: "A long-term administration of probucol and QTc interval prolongation." Artery. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Saku,K.et al: "In vivo conversion of recombinant human proapolipoprotein AI to apolipoprotein AI in rabbits" Biochimica et Biophysica Acta. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Liu,R.,Saku,K.et al: "In vivo kinetics of oxidatively modified HDL." Biochemical Medicine Metabolic Biology. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Okura,Y.,Saku,K.et al: "Serum lipoprotein(a) in maintenance hemodialysis patients" Nephron. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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