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CLARIFICATION OF THE BIOLOGICAL MEANING OF MENAQUINONE-4 SYNTHESIS IN ANIMAL ORGANS

Research Project

Project/Area Number 16580095
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

SHIRAKAWA Hitoshi  GRADUATE SCHOOL OF AGRICULTURAL SCIENCE, TOHOKU UNIVERSITY, ASSOCIATE PROFESSOR, 大学院農学研究科, 助教授 (40206280)

Co-Investigator(Kenkyū-buntansha) KOMAI Michio  GRADUATE SCHOOL OF AGRICULTURAL SCIENCE, PROFESSOR, 大学院農学研究科, 教授 (80143022)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsvitamin K / menaquinone-4 / anti-inflammation / gene regulation / steroidogenesis / 食品 / 生体内変換 / 抗炎症 / DNAマイクロアレイ
Research Abstract

Vitamin K (K) is well known for its role in post-translational activation of a family of nascent proteins to Gla-proteins, such as blood clotting factors and bone Gla-proteins. There are two forms of naturally occurring K: Ki, plant-synthesized phylloquinone; and K2, a family of homologues designated as menaquinone-n (MK-n), which are synthesized by microorganisms including intestinal microflora. However, reports indicate that K analogues are converted into MK-4 in various organs outside the gastrointestinal tract without involvement of bacterial enzymes. Although studies indicate that MK-4 has unique functions related to cell differentiation, induction of apoptosis, and stimulation of transcription of a ligand for the nuclear receptor, these cannot totally explain the physiological significance of MK-4 synthesis in diverse tissues. To help elucidate the biological role of MK-4 production, we used germfree rats to eliminate MK-n synthesized by intestinal flora, and identified patterns of gene expression as a function of K status.
Wistar germfree rats were fed either K-deficient, Control (normal level of 1(1), Ki-supplemented, or MK-4-supplemented diets. We obtained testicular gene expression profiles using DNA microarray techniques. Expression of genes involved in cholesterol synthesis and isoprenoid metabolism was down-regulated in the K-deficient group compared with Ki-supplemented animals. Quantitative RT-PCR analysis revealed that testicular MK-4 concentrations were positively correlated with expression of CYP11a, a rate-limiting enzyme involved in testicular testosterone synthesis. Moreover, plasma testosterone concentrations were reduced in K-deficient relative to Control and MK-4-supplemented animals. Together, these results suggest that testicular MK-4 could be a key factor involved in steroid hormone synthesis via regulation of gene expression related to steroidogenesis.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004

All Journal Article (14 results)

  • [Journal Article] Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat.2006

    • Author(s)
      Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M
    • Journal Title

      Biosci.Biotechnol.Biochem. 70

      Pages: 926-932

    • NAID

      10018532464

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat.2006

    • Author(s)
      Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M.
    • Journal Title

      Biosci. Biotechnol. Biochem. 70

      Pages: 926-932

    • NAID

      10018532464

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat.2006

    • Author(s)
      Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M
    • Journal Title

      Biosci.Biotechnol.Biochem 70(in press)

    • NAID

      10018532464

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Vitamin K can suppress the inflammation induced by lipopolysaccharide administration2005

    • Author(s)
      H Shirakawa, Y Ohsaki, K Hiwatashi, Y Furukawa, T Mizutani, M Komai
    • Journal Title

      J.Hard Tissue Biol. 14

      Pages: 284-285

    • NAID

      110005853564

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 無菌ラットを用いた遺伝子発現の網羅的解析によるメナキノン・4標的遺伝子の検索2005

    • Author(s)
      大崎雄介, 白川仁, 佐藤俊郎, 駒井三千夫
    • Journal Title

      無菌生物 35

      Pages: 142-145

    • NAID

      10016727061

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Vitamin K can suppress the inflammation induced by lipopolysaccharide administration2005

    • Author(s)
      Hitoshi Shirakawa, Yusuke Ohsaki, Kazuyuki Hiwatashi, Yuji Furukawa, Takeo Mizutani, Michio Komai.
    • Journal Title

      J. Hard Tissue Biol. 14

      Pages: 284-285

    • NAID

      110005853564

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ohsaki Y, Shirakawa H, Sato T, Komai M. Clarification of genes regulated by menaquinone-4 using genome-wide expression analysis in germfree rats2005

    • Author(s)
      Ohsaki Y, Shirakawa H, Sato T, Komai M.
    • Journal Title

      J. germfree life gnotobiol. 35

      Pages: 142-145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 無菌ラットを用いた遺伝子発現の網羅的解析によるメナキノン-4標的遺伝子の検索2005

    • Author(s)
      大崎雄介, 白川仁, 佐藤俊郎, 駒井三千夫
    • Journal Title

      無菌生物 35

      Pages: 142-145

    • NAID

      10016727061

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 無菌ラットを用いた遺伝子発現の網羅的解析によるビタミンK新規作用の検索2004

    • Author(s)
      大崎雄介, 白川仁, 駒井三千夫
    • Journal Title

      無菌生物 34

      Pages: 103-106

    • NAID

      10013704476

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 無菌動物を使用したビタミンKの新規作用の検索2004

    • Author(s)
      白川仁, 大崎雄介, 峰岸慶彦, 駒井三千夫
    • Journal Title

      無菌生物 34

      Pages: 45-47

    • NAID

      10013226056

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clarification of novel functions of vitamin K using genome-wide expression analysis in germfree rats.2004

    • Author(s)
      Ohsaki Y, Shirakawa H, Komai M.
    • Journal Title

      J. germfree life gnotobiol. 34

      Pages: 103-106

    • NAID

      10013704476

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 無菌ラットを用いた遺伝子発現の網羅的廃析によるビタミンK新規作用の検索2004

    • Author(s)
      大崎雄介, 白川仁, 駒井三千夫
    • Journal Title

      無菌生物 34

      Pages: 103-106

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 無菌動物を使用したビタミンKの新規作用の検索2004

    • Author(s)
      白川仁, 大崎雄介, 峯岸慶彦, 駒井三千夫
    • Journal Title

      無菌生物 34

      Pages: 45-47

    • NAID

      10013226056

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 酸化ストレスによる神経細胞のアポトーシスを阻害するビタミンKの作用2004

    • Author(s)
      白川仁, 駒井三千夫
    • Journal Title

      ビタミン 77

      Pages: 147-150

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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