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Biochemical studies of Lowe's syndrome

Research Project

Project/Area Number 61440090
Research Category

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

Allocation TypeSingle-year Grants
Research Field 代謝生物化学
Research InstitutionKyoto Sangyo University (1989)
Kyoto University (1986-1988)

Principal Investigator

YAMASHINA Ikuo  KYOTO SANGYO UNIV., FAC. OF ENGINEERING, PROFESSOR, 工学部, 教授 (70025675)

Co-Investigator(Kenkyū-buntansha) SUGAHARA Kazuyuki  KYOTO UNIV., FAC. OF PHARM. SCI., ASSISTANT, 薬学部, 助手 (60154449)
FUNAKOSHI Ikuo  KYOTO SANGYO UNIV., FAC. OF ENGINEERING, PROFESSOR, 工学部, 教授 (10025702)
Project Period (FY) 1986 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥29,700,000 (Direct Cost: ¥29,700,000)
Fiscal Year 1989: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1988: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1987: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1986: ¥12,600,000 (Direct Cost: ¥12,600,000)
KeywordsLow's Syndrome / Nucleotide Pyrophosphatase (NPPase) / Phosphodiesterase I / Active Sulfate (PAPS) / Primary Structure of NPPase / Genomic DNA of NPPase / Elevation of Enzyme Activity in a Genetic Disease / Transcription and Translation Relevant to Elevation of Enzyme Activity / ロー症候群 / ヌクレオチドピロホスファターゼ / 先天性代謝異常 / ヌクレオチドピロホスファターゼ遺伝子 / ヒト繊維芽細胞cDNAライブラリー / ヒト線維芽細胞cDNAライブラリー / Lowe症候群 / 糖タンパク質
Research Abstract

Lowe's synarome is a genetic disease with very serious symptoms. We have investigated the biochemical etiology of this disease. Initially we discovered the disorder of glycosaminoglycan sulfation which turned out to be due to enhanced degradation of active sulfate, PAPS. The enzyme which is involved in the PAPS degradation was then identified as nucleotide pyrophosphatase (NPPase) or phosphodiesterase I. The enzyme was purified from human placenta with several steps including the use of a monoclonal antibody to homogeneity. The amounts of the enzyme in fibroblasts from patients and normal individuals were assayed with the use of rabbit anti-NPPase antiserum, and it was found that the enzyme activities in the cells were proportional to the amount of the enzyme.
To obtain a clue to reveal the mechanism to cause the elevation of NPPase in the patients' cells, we have tried to clone the gene encoding NPPase. Nucleotide probes were synthesized based on the sequences of peptides obtained from the purified NPPase by enzymatic digestion. The probes were used to clone cDNA coding the NPPase polypeptide. The longest cDNA had a size of about 3 kb which corresponded to most of the polypeptide except for a small N-terminal region. This cDNA was sequenced. A primer extension method was applied to obtain cDNA corresponding to the N-terminal region plus leader peptide region, which led to elucication of whole amino acid sequence of NPPase. Using the longest cDNA, the amount of MRNA in fibroblasts were determined, and it was found that the amount of enzyme was proportional to the amount of mRNA. Although the mechanism of the elevation of NPPasw in patients' cells has not yet been revealed, the chromosomal location of NPPase and results of other genetic analyses will lead to understanding of biochemical etiology of Lowe's syndrome.

Report

(5 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Toshiro Yano: "Immunoaffinity purification and characterization of nucleotide phrophosphatase from human placenta" Biochem.Biophys.Res.Commun.147. 1061-1069 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazutoshi Horie: "Elevated nucleotide phrophosphatase activity in cultured skin fibroblasts from patents with Lowe's syndrome" Clin.Chim.Acta. 177. 41-48 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 堀江和敏: "Lowe症候群患者細胞中のヌクレオチドピロホスファタ-ゼに関する研究" 生化学. 58. 785 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 矢野敏朗: "ヌクレオチドピロホスファタ-ゼ:その性質とLowe症候群との関係" 生化学. 59. 786 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 船越育雄: "ヒトのヌクレオチドピネルホスファタ-ゼcDNAのクロ-ニングと塩基配列" 生化学. 61. 1142 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Toshiro Yano,: "Immunoaffinity purification and characterization of nucleotide phrophosphatase from human placenta" Biochem. Biophys. Res. Commun.147. 1061-1069 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazutoshi Horie: "Elevated nucleotide phrophosphatase activity in cultured skin fibroblasts from patents with Lowe's syndrome" Clin. Chim. Acta 177, 41-48, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazutoshi Horie: "Studies on nucleotide pyrophosphatase of cultured skin fibroblasts from Lowe's syndrome patients" Seikagaku, 58-8, 785, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Toshiro Yano: "Nucleotide pyrophosphatase: Its properties and correlation to Lowe's syndrome" Seikagaku, 59-8, 786, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ikuo Funakoshi: "Cloning and sequence analysis of cDNA encoding human nucleotide pyrophosphatase" Seikagaku, 61-9, 1142, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Toshiro Yano: "Immunoaffinity purification and characterization of nucleotide phrophosphatase from human placenta" Biochem.Biophys.Res.Commun.147. 1061-1069 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kazutoshi Horie: "Elevated nucleotide phrophosphatase activity in cultured skin fibroblasts from patents with Lowe's syndrome" Clin.Chim.Acta. 177. 41-48 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] 堀江和敏: "Lowe症候群患者細胞中のヌクレオチドピロホスファタ-ゼに関する研究" 生化学. 58. 785 (1986)

    • Related Report
      1989 Annual Research Report
  • [Publications] 矢野敏朗: "ヌクレオチドピロホスファタ-ゼ:その性質とLowe症候群との関係" 生化学. 59. 786 (1987)

    • Related Report
      1989 Annual Research Report
  • [Publications] 船越育雄: "ヒトのヌクレオチドピルホスファタ-ゼcDNAのクロ-ニングと塩基配列" 生化学. 61. 1142 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Toshiro Yano: Biochem.Biophys.Res.Commun.147. 1061-1069 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kazutoshi Horie: Clin.Chim.Acta. 177. 41-48 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Toshiro Yano: Biochem. Biophys. Res. Commun.147. 1061-1069 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Kazutoshi Horie: Clin. Chim. Acta.

    • Related Report
      1987 Annual Research Report
  • [Publications] 矢野敏朗: Journal of Biochemistry. 98. 1097-1107 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] 小堤保則: Journal of Biochemistry. 99. 1253-1265 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 小堤保則: Journal of Biochemistry. 100. 505-512 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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