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Physiological significance of pyruvate kinase isozymes in erythrocyte.

Research Project

Project/Area Number 11670153
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNIHON UNIVERSITY

Principal Investigator

KANNO Hitoshi  Nihon University, School of Medicine, Assistant Professor, 医学部, 講師 (70221207)

Co-Investigator(Kenkyū-buntansha) MIWA Shiro  Okinaka Memorial Institute for Medical Research, Professor Emeritus, 顧問研究員 (40034954)
AIZAWA Shin  Nihon University, School of Medicine, Associate Professor, 医学部, 助教授 (30202443)
NAKAGAWA Shigeki  Nihon University, School of Medicine, Professor, 医学部, 教授 (40059465)
OYAIZU Naoki  Tokyo Medical and Denatal University, Dept.Retroviral Regulation, Associate Professor, 医学部, 助教授 (00282773)
KOIZUMI Tsutomu  Fukui Medical University, Experimental Animal Center, Associate Professor, 動物実験施設, 助教授 (40126579)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordshemolytic anemia / apoptosis / glycolysis / reactive oxygen species / disease model animals / Friend cells / 遺伝子治療 / トランスジェニックマウス
Research Abstract

Pyruvate kinase (PK) is a rate-limiting enzyme of the glycolytic pathway and PK deficiency is one of the most prevalent causes of hereditary non-spherocytic hemolytic anemia. The Pk-1^<slc> mouse is found to be a spontaneous mutant of the murine LR-type PK gene, and manifests hemolytic anemia and splenomegaly. We showed that apoptotic cells were notably increased in spleen of the Pk-1^<slc> by the TUNEL method, and that the erythroid-specific expression of normal PK gene ameliorated apoptosis in the genetic rescue experiment. Flow cytometric analysis showed that Annexin V / Ter119-double positive cells were significantly increased in the Pk-1slc mouse compared to wild type CBA mice, confirming apoptotic cells were of erythroid lineage. In this study, we examined a physiological role of glycolysis upon apoptosis of the erythroid cells using two Friend erythroleukemic cells, SLC and CBA.These cell lines have been establushed from the Pk-1^<slc> and a wild-type CBA mouse, respectively. As previously reported, apoptosis spontaneously occurred in the Friend cells and was inducible in both cells by glucose deprivation or 0.1-20mM 2-deoxyglucose (2DG). SLC cells were more susceptible to apoptosis by either shorter exposure to glucose deprivation or lower 2DG concentration. The detailed mechanism are still unclear, but we have shown that reactive oxygen species (ROS) might be accountable for these apoptotic changes.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kanno H: "Hexokinase : gene structure and mutations"Baillieres Best Pract Res Clin Haematol. 13. 83-88 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Taguchi M: "Molecular cloning and expression profiles of rat myocilin"Molec Genet Metab. 70. 75-80 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo M: "Heterogeneous mutations in the glycogen- debranching enzyme gene are responsible for glycogen storage disease typeIIIa in Japan"Hum Genet. 106. 108-115 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aizawa S: "Effects of cyclic polylactate (CPL) on the growth of cloned leukenic cells in vitro"Hematol Oncol. 18. 51-60 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirono A: "Molecular and metabolic bases of inherited diseases (8th edition)"McGraw-Hill. 6338 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo M, Horinishi A, Hashimoto M, Kanno H, Murase T: "Glycogen storage disease III subtypes and muscle weakness during childhood."Hum Genet. 104. 112 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aisaki K, Kanno H, Oyaizu N, Hara Y, Miwa S, Ikawa Y: "Apoptotic changes precede mitochondrial dysfunction in red cell type-pyruvate kinase mutant murine erythroleukemia cell lines."Jpn J Cancer Res. 90. 171-179 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami K, Kanno H, Miwa S, Piomelli S: "Human HK_R isozyme : the organization of the Hexokinase-I gene, the erythroid-specific promoter and transcription initiation site."Mol Genet Metab. 67. 118-130 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirono A, Kanno H, Miwa S, Beutler E: "Pyruvate kinase deficiency and other enzymopathies of the erythrocyte. In : Scriver CR, Beaudet AL, Sly WS, Valle D (eds)"The Metabolic and Molecular Bases of Inherited Disease.. 8^<th> edition.Vol.3.. 4637-4653 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo M, Horinishi A, Takeuchi M, Suzuki Y, Sakura N, Hasegawa Y, Igarashi T, et al: "Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan."Hum Genet. 106. 108-115 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Taguchi M, Kanno H, Kubota R, Miwa S, Shishiba Y, Ozawa K: "Molecular cloning and expression profiles of rat myocilin"Molec Genet Metab. 70. 75-80 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanno H: "Hexokinase : gene structure and mutations."Baillieres Best Pract Clin Haematol. 13. 83-88 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Aizawa S, Shimizu N, Handa H, Hiramoto M, Hoshi H, Nagasu M, Kanno H, et al: "Effects of cyclic polylactate (CPL) on the growth of cloned leukemic cells in vitro."Hematol Oncol. 18. 51-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanno H: "Hexokinase : gene structure and mutations."Baillieres Best Pract Res Clin Haematol.. 13. 83-88 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Taguchi M: "Molecular cloning and expression profiles of rat myocilin."Molec Genet Metab. 70. 75-80 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okubo M: "Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIain Japan."Hum Genet. 106. 108-115 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirono A: "Molecular and metabolic bases of inherited diseases.8th editi on."McGraw-Hill. 6338 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ken-ichi Aisaki: "Apoptotic changes precede mitochondrial dysfunction in red cell type-pyru-vate kinase mutant murine ervthroleukemia cell lines."Jpn J Cancer Res. 90. 171-179 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koko Murakami: "Human HK_R isozyme:the organization of the Hexokinase-I gene, the erythroid-specific promoter and transcription initiation site."Mol Genet Metab. 67. 118-130 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Minoru Okubo: "Glycogen storage disease III subtypes and muscle weakness during childhood"Hum Genet. 104. 112 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Minoru Okubo: "Heterogeneous mutations in the glycogen debranching enzyme gene are resposible for glycogen storage disease type IIIa in Japan."Hum Genet. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hitoshi Kanno: "Hexokinase(HX): gene structure and mutations. in Inherited Disorders of Red Cell Metabolism."PAPID MEDICAL MEDIA, Eastbourne, U.K. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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

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