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Preventive function of antioxidant dipeptides, carnosine and anserine, against brain aging(senescence)

Research Project

Project/Area Number 19580144
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

FUJII Makoto  Kagoshima University, 農学部, 教授 (70041655)

Co-Investigator(Kenkyū-buntansha) HOU De-xing  鹿児島大学, 農学部, 准教授 (90305160)
NAKANO Takayuki  鹿児島純心女子大学, 看護栄養学部, 教授 (30155783)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywordsカルノシン / 脳機能低下抑制 / タウ・タンパク / リン酸化タウ / タンパク / 過酸化脂質 / アポトーシス / βアミロイド / 脳機能の老化 / 活性酸素 / 脳細胞のアポトーシス / 脳の老化 / リポフスチン
Research Abstract

抗酸化能を持つジペプチド、カルノシンは動物筋肉などに20mMの高濃度含まれ、抗酸化能、疲労抑制、pH変動抑制、傷口のコラーゲン産生促進など多くの生理機能が知られている。高齢化社会の中で脳機能の劣化は生活QOLの低下が著しいことから、抗酸化能を示す食品成分で脳機能の老化、劣化を抑制することを検討しており、本プロジェクトではカルノシンの脳機能の老化抑制効果を検討した。
1、カルノシンをラットに8ヶ月間投与したところ、脳組織の過酸化脂質量、老人色素、リポフスチン含量は低下し、脳組織の細胞機能の生化学マーカーであるタウ・タンパクのリン酸化程度は減少した。以上より、カルノシンの長期摂取により、脳の活性酸素発生が抑制され脳細胞の正常性がより維持されている、即ち、脳の老化が抑制されていることが示唆された。
2、モデル神経細胞PC12を培養し、過酸化水素を添加すると活性酸素を細胞内に生じてアポトーシスを誘発するが、事前にカルノシン処理しておくと、この活性酸素の産生が抑制され、アポトーシス誘導が抑制される。
3、PC12細胞を培養時にβアミロイドを添加すると、活性酸素を細胞内に生じてアポトーシスを誘発するが、事前にカルノシン処理しておくと、この活性酸素の産生が抑制され、アポトーシス誘導が抑制される。
4、カルノシンを経口投与すると、血中への吸収・移行は投与後1時間をピークとし、その後は減少する。投与したカルノシンは、ほとんどがジペプチドのままで血中に出現した。
5、カルノシンを経口投与し、脳内のカルノシン含量への効果を検討したが、脳内のカルノシン含量の変動は検出できなかった。
6、ラット頭部にドリルで穴を開け、海馬にβアミロイドを注入したラットを用いて、電撃刺激に対する記憶能を検討した。カルノシン投与による改善効果を検討したが、今回の実験では、記憶の成立が確認できなかった。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (45 results)

All 2009 2008 2007

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (32 results)

  • [Journal Article] Akt is a direct target for myricetin to inhibit cell transformation.2009

    • Author(s)
      Kumamoto T, Fujii M, Hou DX
    • Journal Title

      Molecular and Cellular Biochemistry (In press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acetyl derivate of quercetin increases the sensitivity of human leukemia cells toward apoptosis2009

    • Author(s)
      Sakao K, Fujii M, Hou DX
    • Journal Title

      BoFactors (In press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clarification of the role of quercetin hydroxyl groups on superoxide generation and cell apoptosis by chemical modification2009

    • Author(s)
      Sakao K, Fujii M, Hou DX
    • Journal Title

      Biosci Biotechnol Biochem (In press)

    • NAID

      10027545783

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Myricetin directly targets JAK1 to inhibit cell transformation2009

    • Author(s)
      Kumamoto T, Fujii M, Hou DX
    • Journal Title

      Cancer Lett. 275

      Pages: 17-26

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression profiling of genes targeted by bilberry (Vaccinium myrtillus) in macrophages through DNA microarray2008

    • Author(s)
      Chen J, Uto T, Tanigawa S, Kumamoto T, Fujii M, Hou DX
    • Journal Title

      Nutr. Cancer 60

      Pages: 43-50

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanism of apoptosis induced by schizandrae-derived lignans in human leukemia HL-60 cells2008

    • Author(s)
      Lin S, Fujii M, Hou DX
    • Journal Title

      Food Chem Toxicol 46(2)

      Pages: 590-597

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in HepG2 cells2008

    • Author(s)
      Tanigawa S, Fujii M, Hou DX
    • Journal Title

      Biosci. Biotechnol. Biochem. 72(3)

      Pages: 797-804

    • NAID

      10027525776

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanism of apoptosis induced by schizandrae-derived lignans in human leukemia HL-60 cells.2008

    • Author(s)
      Lin S, Fujii M, Hou DX
    • Journal Title

      Food Chem. Toxicol. 46

      Pages: 590-597

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in Hep G2 cells2008

    • Author(s)
      Tanigawa, M. Fujii, D-X. Hou
    • Journal Title

      Biosci. Biotechnol. Biochem., 72 (3) 797-804, 2008 72

      Pages: 797-804

    • NAID

      10027525776

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by querce tin.2007

    • Author(s)
      Tanikawa S, Fujii M, Hou DX
    • Journal Title

      Free Radical Bio. Med., 42

      Pages: 1690-1703

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Green tea proanthocyanidins inhibit cyclooxygenase-2 expression in LPS-activated mouse macrophages: molecular mechanisms and structure-activity relationship2007

    • Author(s)
      Hou DX, Masuzaki S, Uto T, H ashimoto F, Tanikawa S, Fujii M, Sakata Y
    • Journal Title

      Arch. Biochem. Biophys 460

      Pages: 67-74

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prodelphinidin B-4 3'-O-gallate, a tea polyphenol, is involved in the inhibition of COX-2 and iNOS via the downregulation of TAK1-NF-kB path way.2007

    • Author(s)
      Hou DX, Dong Luo, Tanikawa S, Hashimoto F, Uto T, Masuzaki S, Fujii M, Sakata Y
    • Journal Title

      Biochem. Pharm., 74: 742-752 (2007). 74

      Pages: 742-752

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of 6- (methylsulfinyl) hexyl isothiocyanate on cyclooxygenase-2 expression induced by lipopolysaccharide, interferon-gamma and 12-O-tetrad ecanoylphorbol-13-acetate2007

    • Author(s)
      Uto T, Fujii M, Hou DX
    • Journal Title

      Oncol Rep. 17

      Pages: 233-238

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chemical modification and the structure-activity relationships of quercetin derivatives2009

    • Author(s)
      Kozue Sakao , Makoto Fujii, De-Xing Hou
    • Organizer
      日本農芸化学会2009年大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] PI3K/Aktを分子標的としたミリセチンの細胞形質転換抑制2009

    • Author(s)
      隈元拓馬、藤井信、侯徳興
    • Organizer
      日本農芸化学会2009年大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] DNAマイクロアレイを用いたケルセチンの神経保護作用の解析2009

    • Author(s)
      谷川俊祐、藤井信、侯徳興
    • Organizer
      日本農芸化学会2009年大会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] 黒糖焼酎粕のメラニン形成抑制効果とその機構解析2008

    • Author(s)
      斎藤ゆず、比嘉淳、園田直、原暁穂、侯徳興、山本雅史、藤井信
    • Organizer
      第13回日本フードファクター学会大会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] ミリセチンはJAK1を分子標的として細胞形質転換を抑制する2008

    • Author(s)
      隈元拓馬、藤井信、侯徳興
    • Organizer
      第13回日本フードファクター学会大会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] ケルセチンによる転写因子のユビキチン化及び安定化の制御 : ポリフェノールの新たな機能性2008

    • Author(s)
      谷川俊祐、藤井信、侯徳興
    • Organizer
      第13回日本フードファクター学会大会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] COX-2及びiNOSを標的としたワサビ成分の抗炎症作用2008

    • Author(s)
      大黒洋佑、藤井信、侯徳興
    • Organizer
      第62回日本栄養・食糧学会大会
    • Place of Presentation
      埼玉
    • Related Report
      2008 Final Research Report
  • [Presentation] DNAマイクアレーを用いたアントシアニンの抗炎症作用の網羅的な解析2008

    • Author(s)
      陳継華、藤井信、侯徳興
    • Organizer
      第62回日本栄養・食糧学会大会
    • Place of Presentation
      埼玉
    • Related Report
      2008 Final Research Report
  • [Presentation] ポリフェノールのタンパク質ユビキチン化に及ぼす影響 : ケルセチンを例として2008

    • Author(s)
      侯徳興、谷川俊祐、藤井信
    • Organizer
      第62回日本栄養・食糧学会大会
    • Place of Presentation
      埼玉
    • Related Report
      2008 Final Research Report
  • [Presentation] ワカメフコイダンの免疫亢進機能の解析2007

    • Author(s)
      石井朝子、侯 徳興、藤井 信
    • Organizer
      第61回日本栄養・食糧学会大会
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Cytoprotective role of quercetin through modulating Nrf2/Keap1 system2007

    • Author(s)
      Shunsuke Tanigawa, Makoto Fuiii and De-Xing Hou
    • Organizer
      12th World Congress on Advances in Oncology and 10th International Symposium on Molecular Medicine and Cancer Chemoprevention Symposium.
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] メカブフコイダンによる免疫能促進作用の解析、2007

    • Author(s)
      石井朝子、侯 徳興、藤井 信
    • Organizer
      第54回日本食品科学工学会
    • Place of Presentation
      福岡
    • Related Report
      2007 Annual Research Report
  • [Presentation] Cytoprotective role of quercetin through modulating Nrf2/Keap1 system. Tea proanthocyanidins exert anti-inflammation through the downre gulation of TAK1-mediated COX-2 and iNOS expression.2007

    • Author(s)
      Jihua Chen, Satoko Masuzaki, Dong Luo, Fumio Hashimoto, Shunsuke Tanigawa, Makoto Fujii, Yusuke Sakata2, De-Xing Hou:
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anthocyanins and Health: Chemopreventive Activities and Molecular Targets2007

    • Author(s)
      De-Xing Hou, Makoto Fujii (招待講演)
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Ampelopsin, a polyphenolic compound from a bayberry, induces apoptosis in human leukemia cells.2007

    • Author(s)
      Kozue Sakao, Mayumi Kobo, Akiko Morishita, Fumio Hashimoto, Yusuke Sakata, Makoto Fujii, De-Xing Hou
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Quercetin, a typical dietary polyphenol, exerts cytoprotective effects by modulating Nrf2 and Keap1.2007

    • Author(s)
      Shunsuke Tanigawa, Makoto Fujii, De-Xing Hou
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Chemopreventive activities and molecular targets of myricetin: evidence from cellular investigation.2007

    • Author(s)
      Takuma Kumamoto, Makoto Fujii, De-Xing Hou:
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Spice ursolic acid induces apoptosis in human colon cancer cells (LoVo)2007

    • Author(s)
      Akiko Morishita, Mayumi Kubo, Makoto Fujii, De-Xing Hou:
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anti-ageing activities of carnosine againt brain function.2007

    • Author(s)
      Yasuhiro Tanaka, Shin-ichi Eguchi, Yoshihiro Yoshida, De-Xing Hou, Makoto Fujii:
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anti-hyperglycemic effects of Kurozu (brewed rice vinegar produced by an traditional method in Kagoshima, Japan) on KK-Ay mice, a non-insulin-dependent diabetes mellitus model2007

    • Author(s)
      Tomoko Ueno, Masanobu Nagano, De-Xing Hou, Makoto Fujii
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anti-tumor activity of fucoidan, sulfated polysaccharide from brown algae.2007

    • Author(s)
      Asako Ishii, De-Xing Hou, Akira Ikem, Makoto Fujii.
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Apotosis-inducing material from Cladosiphan okamuranus (Okinawa Mozuku)2007

    • Author(s)
      Kana Inohara, Akiko Morishita, Masaji Nakamizo, De-Xing Hou, Makoto Fujii
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Apoptosis-inducing material produced in baked sweet potato, Ipomoea Batats L.(Kogane-Semgan)2007

    • Author(s)
      Isselmou Ould Rabah, Fumio Hashimoto, De-Xing Hou, Shin-Ichi Komine, Makoto Fujii
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Preventive effect of carnosine and bonito soup on diabetic cataract2007

    • Author(s)
      Shin-Ichi Eguchi, De-Xing Hou, and Makoto Fujii
    • Organizer
      The Satellite Symposium of ICPH2007
    • Place of Presentation
      鹿児島
    • Related Report
      2007 Annual Research Report
  • [Presentation] Apotosis-inducing material from Cladosiphan okamuranus (Okinawa Mozuku) Tea, proanthocyanidins are involved in the inhibition of COX-2 and iNOS via the downregulation of TAK1-mediated NF-kB and MAPK signaling.2007

    • Author(s)
      Jihua Chen, Fumio Hashimoto, Satoko Masuzaki, Dong Luo, Shunsuke Tanigawa, Takuhiro Uto, Makoto Fujii, Yusuke Sakata, De-Xing Hou
    • Organizer
      3rd International Conference on Polyphenols and Health (ICPH2007)
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular mechanism of the inhibition of EGF-induced cell transformation by myricetin2007

    • Author(s)
      Takuma Kumamoto, Makoto Fujii, De-Xing Hou:
    • Organizer
      3rd International Conference on Polyphenols and Health (ICPH2007)
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Quercetin stimulates antioxidant responsive element (ARE) through modulating Nrf2 and Keap12007

    • Author(s)
      Shunsuke Tanigawa, Makoto Fujii, De-Xing Hou:
    • Organizer
      3rd International Conference on Polyphenols and Health (ICPH2007)
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Ampelopsin induces apoptosis in HL-60 cell through ROS-mediated mitochondrial death pathway2007

    • Author(s)
      Kozue Sakao, Mayumi Kobo, Akiko Morishita, Fumio Hashimoto, Yusuke Sakata, Makoto Fujii, De-Xing Hou:
    • Organizer
      3rd International Conference on Polyphenols and Health (ICPH2007)
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Quercetin acts as a small molecule inhibitor of HDM2 to induce p53-dependent apoptosis in HepG2 cells2007

    • Author(s)
      Shunsuke Tanigawa, Makoto Fujii, De-Xing Hou:
    • Organizer
      International Conference on Food Factors for Health Promotion (ICOFF2007).
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anti-ageing activities of carnosine againt brain function2007

    • Author(s)
      Yasuhiro Tanaka, Shin-ichi Eguchi, Yoshihiro Yoshida, De-Xing Hou, Makoto Fujii:
    • Organizer
      International Conference on Food Factors for Health Promotion (ICOFF2007)
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anti-ageing activities of carnosine againt brain function2007

    • Author(s)
      Yasuhiro Tanaka, Shin-ichi Eguchi, Yoshihiro Yoshida, De-Xing Hou, Makoto Fujii
    • Organizer
      International Conference on Food Factors for Health Promotion (ICOFF2007).
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anthocyans-more than nature's color: Chemopreventive activities and molecular targets.2007

    • Author(s)
      De-Xing Hou, Makoto Fujii, Makoto Yoshimoto, Norihiko Terahara
    • Organizer
      12th World Congress on Advances in Oncology and 10th International Symposium on Molecular Medicine and Cancer Chemoprevention Symposium.
    • Place of Presentation
      Creta Maris Hotel, Hersonissos, Crete, Greece
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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