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Novel function of menaquinone-4 in brain

Research Project

Project/Area Number 17H03814
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionTohoku University

Principal Investigator

SHIRAKAWA HITOSHI  東北大学, 農学研究科, 教授 (40206280)

Co-Investigator(Kenkyū-buntansha) 駒井 三千夫  東北大学, 農学研究科, 名誉教授 (80143022)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
KeywordsビタミンK / メナキノン-4 / 脳機能 / 海馬 / 栄養学 / 痴呆 / 食品
Outline of Final Research Achievements

Naturally occurring vitamin K (VK) is phylloquinone and menaquinones. A part of ingested VK from the diet is converted to menaquine-4, but the biological meaning of this conversion has not been fully elucidated specially in brain. In this study, we analyzed the role of menaquinone-4 on the activation of protein kinase A and the suppression of inflammation using cognition impaired mice, normal rats and cultured microglia. Feeding of VK deficient diet to dementia model mice enhanced cognition impairment. VK supplemented diet in normal rats activated protein kinase A, and elevated the expression of neurotrophic factor in hippocampus. Menaquinone-4 suppressed lipopolysaccharide-induced inflammatory cytokine expression in mouse derived microglia via the inhibition of activation NF kappa B. These results lead to be understood the biological importance of VK conversion in brain.

Academic Significance and Societal Importance of the Research Achievements

メナキノン-4は炎症刺激によるミクログリアの炎症性サイトカイン発現を抑制すること、その作用機序としてNFκBの活性化抑制によることを明らかにした。アルツハイマー病をはじめ、脳神経疾患の発症・増悪には慢性炎症が関与していることから、脳内のメナキノン-4は抗炎症作用を示し、疾病予防に関与している可能性がある。また、高VK食の摂取により脳内の神経栄養因子の発現量が増加し、これがAキナーゼの活性化によることが示唆された。食品からVK摂取は、認知機能を含む脳機能を向上させる可能性があり、新たなサプリメント等の開発に繋がる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (30 results)

All 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (22 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Menaquinone-4 Amplified Glucose-Stimulated Insulin Secretion in Isolated Mouse Pancreatic Islets and INS-1 Rat Insulinoma Cells2019

    • Author(s)
      Ho Hsin-Jung、Shirakawa Hitoshi、Hirahara Keisukei、Sone Hideyuki、Kamiyama Shin、Komai Michio
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 8 Pages: 1995-1995

    • DOI

      10.3390/ijms20081995

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Menaquinone-4 Suppresses Lipopolysaccharide-Induced Inflammation in MG6 Mouse Microglia-Derived Cells by Inhibiting the NF-κB Signaling Pathway2019

    • Author(s)
      Saputra Wahyu Dwi、Aoyama Nao、Komai Michio、Shirakawa Hitoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 9 Pages: 2317-2317

    • DOI

      10.3390/ijms20092317

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Geranylgeraniol Suppresses the Expression of IRAK1 and TRAF6 to Inhibit NFκB Activation in Lipopolysaccharide-Induced Inflammatory Responses in Human Macrophage-Like Cells2019

    • Author(s)
      Giriwono PE, Shirakawa H, Ohsaki Y, Sato S, Aoyama Y, Ho H-J, Goto T, Komai M
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 20 Issue: 9 Pages: 2320-2330

    • DOI

      10.3390/ijms20092320

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel function of geranylgeraniol in regulating testosterone production2018

    • Author(s)
      Ho Hsin-Jung、Shirakawa Hitoshi、Giriwono Puspo E.、Ito Asagi、Komai Michio
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 82 Issue: 6 Pages: 791-797

    • DOI

      10.1080/09168451.2017.1415129

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ゲラニルゲラニオールの作用と最近の話題2018

    • Author(s)
      白川仁、何欣蓉、駒井三千夫
    • Journal Title

      オレオサイエンス

      Volume: 18 Pages: 99-106

    • NAID

      130007700757

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of novel silanol-based human pregnane X receptor (PXR) agonists with improved receptor selectivity.2018

    • Author(s)
      Toyama H, Shirakawa H, Komai M, Hashimoto Y, Fujii S.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 26 Issue: 15 Pages: 4493-4501

    • DOI

      10.1016/j.bmc.2018.07.038

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Vitamin K2 on the Expression of Genes Involved in Bile Acid Synthesis and Glucose Homeostasis in Mice with Humanized PXR.2018

    • Author(s)
      Sultana H, Watanabe K, Rana MM, Takashima R, Ohashi A, Komai M, Shirakawa H.
    • Journal Title

      Nutrients

      Volume: 10 Issue: 8 Pages: 982-982

    • DOI

      10.3390/nu10080982

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Menquinone-4 enhances steroidogenesis in testis derived tumor cells via the elevation of cAMP level.2017

    • Author(s)
      Ho H-J, Shirakawa H, Komai M.
    • Journal Title

      Vitamin K2 - Vital for Health and Wellbeing

      Volume: 1 Pages: 189-198

    • DOI

      10.5772/63982

    • ISBN
      9789535130192, 9789535130208
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト型PXRマウスを用いたメナキノン-4による遺伝子発現調節機構の解析2019

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、駒井三千夫
    • Organizer
      日本ビタミン学会第71大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ラットへのビタミンK給餌が海馬の遺伝子発現に及ぼす影響2019

    • Author(s)
      片倉しおり、岡田奈緒、白川仁、駒井三千夫
    • Organizer
      日本ビタミン学会第71大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Vitamin K2 attenuates the lipopolysaccharide-induced inflammation in mouse microglial cells via the inhibition of the NFκB signaling and inflammasome activation2019

    • Author(s)
      Wahyu Dwi Saputra, Nao Aoyama, Michio Komai, Hitoshi Shirakawa
    • Organizer
      Asian Congress of Nutrition 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of the expression of genes involved in bile acid synthesis and glucose homeostasis by vitamin K2 in mice with humanized PXR2019

    • Author(s)
      Sultana Halima、渡邉きみか、錦戸迪哉、Rana Md Masud、 駒井三千夫、白川仁
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ラットへのビタミンK強化食給餌給餌が認知機能関連遺伝子の発現に及ぼす影響2019

    • Author(s)
      片倉しおり、岡田菜緒、大崎雄介、駒井三千夫、白川仁
    • Organizer
      日本栄養・食糧学会東北支部第53回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] トコトリエノール、メナキノンがLS180細胞の薬物代謝遺伝子の発現に及ぼす影響2019

    • Author(s)
      渡邉きみか、加藤綾華、白川仁、駒井三千夫
    • Organizer
      第30回ビタミンE研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト型PXRマウスを用いたビタミンK2によるPXR標的遺伝子の発現調節の解析2019

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、駒井三千夫
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of gene expression by vitamin K2 (MK-4) in humanized PXR mice.2018

    • Author(s)
      Halima Sultana, Kimika Watanabe, Hitoshi Shirakawa, Michio Komai
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] メナキノン-4と薬物との共処理がヒト型PXRマウスの薬物応答遺伝子の発現に及ぼす影響2018

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、駒井三千夫
    • Organizer
      日本ビタミン学会第70回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Vitamin K2 attenuates LPS-induced inflammation in mouse microglial cells2018

    • Author(s)
      Wahyu Dwi Saputra, Nao Aoyama, Hitoshi Shirakawa, Michio Komai
    • Organizer
      日本ビタミン学会第70回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト型PXRマウスの薬物応答遺伝子の発現に及ぼすメナキノン-4と薬物との共処理の影響2018

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、駒井三千夫
    • Organizer
      日本農芸化学会東北・北海道支部合同支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Menaquinone-4 suppresses LPS-induced inflammatory expressions in mouse microglial cells2018

    • Author(s)
      Wahyu Dwi Saputra, 青山奈央、白川仁、駒井三千夫
    • Organizer
      日本農芸化学会東北・北海道支部合同支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effect of oral ingestion of vitamin K2 on the gene expression of drug-metabolism and bile acid synthesis in humanized PXR mice.2018

    • Author(s)
      Sultana H, Watanabe K, Komai M, Shirakawa H
    • Organizer
      Asia-Pacific Nutrigenomics and Nutrigenetics Organization, Biennial Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of dietary ingestion of vitamin K1 derivative (dihydorophylloquinone) on bone metabolism in germ-free rats.2017

    • Author(s)
      Yuskue Ohsaki, Yuta Komano, Hitoshi Shirakawa, Toshiro Sato, Micho Komai
    • Organizer
      The 19th Interntional Symosium on Gnotobilogy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトPXRノックインマウスを用いたビタミンK2による薬物代謝関連遺伝子の発現調節機構の解析2017

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、後藤知子、駒井三千夫
    • Organizer
      日本ビタミン学会第69大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウスミクログリア細胞におけるビタミンKの抗炎症効果の解析2017

    • Author(s)
      青山奈央、白川仁、後藤知子、駒井三千夫
    • Organizer
      日本ビタミン学会第69大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ラットへのビタミンK給餌が海馬のステロイドホルモン産生に及ぼす影響2017

    • Author(s)
      岡田菜緒、白川仁、何欣蓉、後藤知子、駒井三千夫
    • Organizer
      日本ビタミン学会第69大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生殖腺におけるビタミンK欠乏の影響に対する性差の検討2017

    • Author(s)
      大崎雄介、白川仁、伊東あさぎ、駒井 三千夫
    • Organizer
      日本ビタミン学会第69大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effect of the ingestion of vitamin K-deficient diet on glucose metabolism in diabetic model mice.2017

    • Author(s)
      Keisuke Hirahara, Masayori Saito, Puspo E. Giriwono, Tomoko Katsurai, Tomoko Goto, Michio Komai, Hitoshi Shirakawa
    • Organizer
      21st International Congress of Nutrition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Vitamin K regulates the gene expression of drug-metabolizing genes via PXR in human colon cancer cells.2017

    • Author(s)
      Halima Sultana, Ayaka Kato, Tomoko Goto, Michio Komai, Hitoshi Shirakawa
    • Organizer
      21st International Congress of Nutrition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトPXRノックインマウスを用いたメナキノン-4による薬物代謝関連遺伝子の発現変化の解析2017

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、駒井三千夫
    • Organizer
      第51回日本栄養・食糧学会東北支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトPXRノックインマウスを用いたビタミンK2による遺伝子発現調節の解析2017

    • Author(s)
      渡邉きみか、Sultana Halima、白川仁、駒井三千夫
    • Organizer
      2017年生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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