Identification of food-derived neurotrophic factors

• Project/Area Number: 19780094
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Food science
• Research Institution: Nagoya University
• Principal Investigator: SHIBATA Takahiro Nagoya University, 大学院・生命農学研究科, 助教 (80447838)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 神経細胞 / 神経栄養因子 / 食品成分 / 分化 / 神経変性疾患

Research Abstract

本研究では、神経栄養因子であるNGFの作用を代替・増強する食品成分の探索とその 作用機構の分子レベルでの解明を目的として研究を行ってきた。 神経分化のモデル細胞であるPC12細胞を用いたスクリーニングの結果、アブラナ科野菜の中でも特にワサビ抽出物に強い活性を見出した。さらにその活性成分について各種クロマトグラフィーを用いて単離・精製を行い、NGF増強活性を有する成分として6-メチルスルフィニルヘキシルイソチオシアネート(6-HITC)を同定した。さらにその作用機構について詳細な解析を行った結果、6-HITCはNGF受容体を負に制御する脱リン酸化酵素PTP1Bの活性を低下させることによりその活性を発現することが示唆された。さらにそのPTP1Bの不活性化には、6-HITCによる細胞内酸化ストレスの亢進が関与している可能性が考えられた。

Research Products

• [Journal Article] Keap1 regulates the constitutive expression of GST A1 during differentiation of Caco-2 cells. (2008)
  • Author(s): Kusano, Y., Horie, S., Shibata, T., Satsu, H., Shimizu, M., Hitomi, E., Nishida, M., Kurose, H., Itoh, K., Kobayashi, A., Yamamoto, M., and Uchida, K.
  • Journal Title: Biochemistry 47 Pages: 6169-6177
  • Peer Reviewed
• [Journal Article] H_2O_2-Mediated Covalent Modification of Protein by Lipid Peroxidation-Derived Saturated Aldehydes. (2008)
  • Author(s): Ishino, K., Shibata, T., Ishii, T., Liu, Y. T., Toyokuni, S., Zhu, X., Sayre, L. M., and Uchida, K. Protein N Acylation
  • Journal Title: Chem. Res. Toxicol 21 Pages: 1261-1270
  • Peer Reviewed
• [Journal Article] Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. (2008)
  • Author(s): Takahashi, N., Mizuno, Y., Kozai, D., Yamamoto, S., Kiyonaka, S., Shibata, T., Uchida, K., and Mori, Y.
  • Journal Title: Channels (Austin) 2 Pages: 287-298
  • Peer Reviewed
• [Journal Article] A food-derived synergist of NGF signaling: Identification of protein tyrosine phosphatase 1B as a key regulator of NGF receptor-initiated signal transduction. (2008)
  • Author(s): Shibata T, Nakahara H, Kita N, Matsubara Y, Han C, Morimitsu Y, Iwamoto N, Kumagai Y, Nishida M, Kurose H, Aoki N, Ojika M, Uchida K.
  • Journal Title: J. Neurochem. 107 Pages: 1248-1260
  • Peer Reviewed
• [Journal Article] Keapl regulates the constitutive expression of GST Al during differentiation of Caco-2 cells via the formation of E-cadher in-mediated cell-cell adhesion (2008)
  • Author(s): Kusano, Y, et.al.
  • Journal Title: Biochemistry 47 Pages: 6169-6177
  • Peer Reviewed
• [Journal Article] Potein N-acylation : H 2 O 2-induced covalent modification of protein by lipid peroxidation-derived saturated aldehydes (2008)
  • Author(s): Ishino, K, et.al.
  • Journal Title: Chem. Res. Toxicol. 21 Pages: 1261-1270
  • Peer Reviewed
• [Journal Article] A food-derived synergist of NGF signaling : Identification of protein tyrosine phosphatase 1 B as a key regulator of NGF receptor-initiated signal transduction (2008)
  • Author(s): Shibata, T, et.al.
  • Journal Title: J. Neurochem. 170 Pages: 1248-1260
  • Peer Reviewed
• [Journal Article] Molecular characterization of TRPA 1 channel activation by cysteine-reactive inflammatory mediators (2008)
  • Author(s): Takahashi, N, et.al.
  • Journal Title: Channels 2 Pages: 287-298
  • Peer Reviewed
• [Journal Article] Protein-bound 4-hydroxy-2-nonenal: An endogenous triggering antigen of anti-DNA response. (2007)
  • Author(s): Toyoda, K., Nagae, R., Akagwa, M., Ishino, K., Shibata, T., Ito, S., Shibata, N., Yamamoto, T., Kobayashi, M., Takasaki, Y., Matsuda, T., & Uchida, K.
  • Journal Title: J. Biol. Chem. 282 Pages: 25769-78
  • Peer Reviewed
• [Journal Article] Identification of a serum component that regulates cyclooxygenase-2 gene expression in cooperation with 4-hydroxy-2-nonenal. (2007)
  • Author(s): Kanayama, M., Yamaguchi, S., Shibata, T., Shibata, N., Kobayashi, M., Nagai, R., Arai, H., Takahashi, K., & Uchida, K.
  • Journal Title: J. Biol. Chem. 282 Pages: 24166-74
  • Peer Reviewed
• [Journal Article] Dose-dependent differential regulation of cytokine secretion from macrophages by fractalkine. (2007)
  • Author(s): Mizutani, N., Sakurai, T., Shibata, T., Uchida, K., Fujita, J., Kawashima, R., Kawamura, Y. I., Toyama-Sorimachi, N., Imai, T., & Dohi, T.
  • Journal Title: J. Immunol. 179 Pages: 7478-7487
  • Peer Reviewed
• [Journal Article] Protein-bound 4-hydroxy-2-nonenal : an endogenous triggering antigen of anti-DNA response. (2007)
  • Author(s): Toyoda, Y.et al.
  • Journal Title: J.Biol.Chem. 282 Pages: 25769-25778
  • Peer Reviewed
• [Journal Article] Identification of a serum component that regulates cyclooxygenase-2 gene expression in cooperation with 4-hydroxy-2-nonenal. (2007)
  • Author(s): Kanayama, M.et al.
  • Journal Title: J.Biol.Chem. 282 Pages: 24166-24174
  • Peer Reviewed
• [Journal Article] Dose-dependent differential regulation of cytokine secretion from macrophages by Fractalkine. (2007)
  • Author(s): Mizutani, N.et al.
  • Journal Title: J.Immunol. 179 Pages: 7478-7487
  • Peer Reviewed
• [Presentation] Immunochemical detection of a long-lived 4-ketoamide-type 4-oxo-2-nonenal-lysine adduct. (2008)
  • Author(s): Shibata, T., Shimozu, Y., Ishino, K., Wakita, C., Shibata, N., Kobayashi, M., Zhu, X., Sayre, LM., Uchida, K.
  • Organizer: The International Symposium on Lipid Peroxidation 2008
  • Place of Presentation: Karuizawa
  • Year and Date: 2008-10-16
• [Presentation] Immunochemical detection of a long-lived 4-ketoamide-type 4-oxo-2-nonenal-lysine adduct. The International Symposium on Lipid Peroxidation 2008.(Karuizawa) 2008. 10 (2008)
  • Author(s): Shibata, T, et.al.
  • Organizer: The International Symposium on Lipid Peroxidation 2008
  • Place of Presentation: 軽井沢
  • Year and Date: 2008-10-16
• [Presentation] イソチオシアネートによるレドックス制御を介した神経細胞分化促進機構の解析 (2008)
  • Author(s): 柴田貴広、中原寛子、喜多なるみ、松原唯、森光康次郎、岩本典子、熊谷嘉人、青木直人、小鹿一、内田浩二
  • Organizer: 。第61回日本酸化ストレス学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-06-19
• [Presentation] イソチオシアネートによるレドックス制御を介した神経細胞分化促進機構の解析 (2008)
  • Author(s): 柴田貴広, ら
  • Organizer: 日本酸化ストレス学会
  • Place of Presentation: 京都
  • Year and Date: 2008-06-19
• [Presentation] イソチオシアネート化合物による脱リン酸化酵素の制御と神経細胞分化誘導 (2008)
  • Author(s): 柴田貴広、中原寛子、喜多なるみ、松原唯、森光康次郎、熊谷嘉人、青木直人、小鹿一、内田浩二
  • Organizer: 自然科学研究機構基礎生物学研究所研究会"リン酸化シグナルの統合的解明を目指して"
  • Place of Presentation: 岡崎
  • Year and Date: 2008-04-19
• [Presentation] The 4-oxo-2-nonenal-derived ketoamide adduct as a novel biomarker of oxidative stress. (2008)
  • Author(s): Shibata, T., Ishino, K., Shibata, N., Kobayashi, M., Zhu, X., Sayre, L.M., Uchida, K.
  • Organizer: International Symposium "Biomarkers of Oxidative Stress in Health and Diseases"
  • Place of Presentation: Osaka
  • Year and Date: 2008-01-18
• [Presentation] The 4-oxo-2-nonenal-derived ketoamide adduct as a novel biomarker of oxidative stress. (2008)
  • Author(s): Shibata, T.et al.
  • Organizer: International Symposium "Biomarkers of Oxidative Stress in Health and Diseases"
  • Place of Presentation: 大阪
  • Year and Date: 2008-01-17
• [Presentation] 新規脂質過酸化物4-オキソ-2-ノネナールの化学と生物 (2007)
  • Author(s): 柴田貴広, 内田浩二
  • Organizer: 日本過酸化脂質・フリーラジカル学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-09
• [Presentation] 新規脂質過酸化物4-オキソ-2-ノネナールの化学と生物. (2007)
  • Author(s): 柴田貴広、内田浩二
  • Organizer: 日本過酸化脂質・フリーラジカル学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-08
• [Book] "NGF作用増強因子:食べ物による神経細胞機能改善は可能か?" 栄養学研究の最前線 (日本栄養食糧学会監修) (2008)
  • Author(s): 内田浩二、柴田貴広、喜多なるみ、松原唯
  • Publisher: (株)建帛社
• [Book] 「NGF作用増強因子 : 食べ物による神経細胞機能改善は可能か?」栄養学研究の最前線(日本栄養食糧学会監修) (2008)
  • Author(s): 内田浩二, ら
  • Total Pages: 11
  • Publisher: (株)建帛社