Chemical biology on functional foods that activate receptor signaling

• Project/Area Number: 18380078
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Nagoya University
• Principal Investigator: UCHIDA Koji Nagoya University, 大学院・生命農学研究科, 准教授 (40203533)
• Co-Investigator(Kenkyū-buntansha): OJIKA Makoto 名古屋大学, 大学院・生命農学研究科, 教授 (50152492)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥2,160,000); Fiscal Year 2008: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2007: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2006: ¥7,800,000 (Direct Cost: ¥7,800,000)
• Keywords: 神経成長因子 / ケミカルバイオロジー / 受容体活性化 / チロシンホスファターゼ / イソチオシアネート / 神経細胞 / 機能性食品成分 / ポリフェノール / 神経突起伸張

Research Abstract

神経成長因子(Nerve Growth Factor ; NGF)は神経細胞の分化を促進し、その生存を維持する作用のある一群のタンパク質である。NGF受容体TrkAの過剰発現細胞を樹立し、TrkAの脱リン酸化に関与するプロテインチロシンフォスファターゼ(PTP)の同定を行った。方法としてはPTP 発現系を用い、NGF刺激によるTrkAのリン酸化を免疫ブロットにより調べた。その結果、TrkAリン酸化の制御にプロテインホスファターゼPTP1Bが関与していることを初めて明らかにした。

Research Products

• [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., and Uchida, K
  • Journal Title: J. Neurochem 170 Pages: 1248-1260
  • 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 in press
  • Peer Reviewed
• [Journal Article] Macrophage as a target of quercetin glucuronides in human atherosclerotic arteries: Implication in the anti-atherosclerotic mechanism of dietary flavonoids (2008)
  • Author(s): Kawai, K., Nishikawa, T., Shiba, Y., Saito, S., Murota, K., Shibata, N., Kobayashi, M., Kanayama, M., Uchida, K., and Terao, J
  • Journal Title: J. Biol. Chem 283 Pages: 9424-9434
  • Peer Reviewed
• [Journal Article] Keap1 regulates the constitutive expression of GST A1 during differentiation of Caco-2 cells via the formation of E-cadherin-mediated cell-cell adhesion (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] 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, et al.
  • Journal Title: J. Neurochem. 170 Pages: 1248-1260
  • Peer Reviewed
• [Journal Article] Molecular characterization of TRPA1 channel activation by cyste ine-reactive inflammatory mediators. (2008)
  • Author(s): Takahashi, et al.
  • Journal Title: Channels 2 Pages: 287-298
  • Peer Reviewed
• [Journal Article] Macrophage as a target of quercetin glucuronides in human athe rosclerotic arteries : Implication in the anti-atherosclerotic mecha nism of dietary flavonoids. (2008)
  • Author(s): Kawai, et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 9424-9434
  • Peer Reviewed
• [Journal Article] Chemical knockdown of protein tyrosine phosphatase 1B by 1,2-naphthoquinone through covalent modification causes persistent transactivation of epidermal growth factor receptor (2007)
  • Author(s): Iwamoto, N., Sumi, D., Ishii, T., Uchida, K., Cho, A. K., Froines, J. R., and Kumagai, Y
  • Journal Title: J. Biol. Chem 282 Pages: 33396-33404
  • Peer Reviewed
• [Journal Article] Lipid oxidation products and oxidized low-density lipoproteins impair platelet-derived growth factor receptor activity in smooth muscle cells: lmplication in atherosclerosis. (2007)
  • Author(s): Vindis, et. al.
  • Journal Title: Redox Report 12 Pages: 96-100
  • Peer Reviewed
• [Journal Article] Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic latera I sclerosis and its transgenic mouse model. (2007)
  • Author(s): Shibata, et. al.
  • Journal Title: Neuropatholog 27 Pages: 49-61
  • Peer Reviewed
• [Journal Article] Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of the Keap1-Clu3 complex (2006)
  • Author(s): Kobayashi, A., Kang, M.-I., Shibata, T., Uchida, K., and Yamamoto, M
  • Journal Title: Mol. Cell. Biol 26 Pages: 221-229
  • Peer Reviewed
• [Journal Article] Identification of a lipid peroxidation product as a potential trigger of the p53 pathway (2006)
  • Author(s): Shibata, T., Iio, K., Kawai, Y., Shibata, N., Kawaguchi, M., Toi, S., Kobayashi, M., Kobayashi, S., Yamamoto, K., and Uchida, K
  • Journal Title: J. Biol. Chem 281 Pages: 1196-1204
  • Peer Reviewed
• [Journal Article] Desensitization of platelet-derived growth factor receptor-b by oxidized lipids in vascular cells and atherosclerotic lesions. Prevention by Aldehyde Scavengers (2006)
  • Author(s): Vindis, C., Escargueil-Blanc, I., Elbaz, M., Marcheix, B., Grazide, M.-H., Uchida, K., Salvayre, R., and Negre-Salvayre, A
  • Journal Title: Circ. Res 98 Pages: 785-792
  • Peer Reviewed
• [Journal Article] Granulatoside A, a starfish steroid glycoside, enhances the PC12 cell neuritogenesis induced by nerve growth factor through an activation of MAP kinase. (2006)
  • Author(s): Qi, J., et al.
  • Journal Title: Chem. Med. Chem. 1 Pages: 1351-1354
• [Journal Article] Prostaglandins from a zoanthid : Paclitaxel-like neurite-degenerating and microtubule-stabilizating activities. (2006)
  • Author(s): Han et al.
  • Journal Title: Biosci. Biotech. Biochem. 70 Pages: 706-711
• [Journal Article] Polymer-assisted solution-phase synthesis and neurite outgrowth-promoting activity of 15-deoxy-D^<12,14>-PGJ_2 derivatives. (2006)
  • Author(s): Tanaka, H., et al.
  • Journal Title: Chem. Asian J. 1 Pages: 669-677
• [Presentation] 受容体シグナリングを活性化する低分子シネルギスト (2009)
  • Author(s): 内田浩二
  • Organizer: お茶の水女子大学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2009-01-14
• [Presentation] 受容体シグナリングを活性化する低分子シネルギスト (2008)
  • Author(s): 内田浩二
  • Organizer: 京都大学ウィルス研究所セミナー
  • Place of Presentation: 京都
  • Year and Date: 2008-12-19
• [Presentation] 生体内におけるタンパク質の変成と疾病 (2008)
  • Author(s): 内田浩二
  • Organizer: 北海道薬科大学特別講演会
  • Place of Presentation: 小樽
  • Year and Date: 2008-12-05
• [Presentation] 酸化ストレス研究が栄養食糧学にもたらすもの (2008)
  • Author(s): 内田浩二
  • Organizer: 日本栄養食糧学会シンポジウム
  • Place of Presentation: 坂戸
  • Year and Date: 2008-05-02
• [Presentation] 親電子性物質によるケミカルバイオロジー (2008)
  • Author(s): 内田浩二
  • Organizer: 学長重点研究「脳保護に向けたケミカルバイオロジー」シンポジウム
  • Place of Presentation: 弘前
  • Year and Date: 2008-02-15
• [Presentation] 6-Methylsulfinylhexyl isothiocyanate as a multifunctional electrophile (2007)
  • Author(s): Uchida, K
  • Organizer: International Conference on Food Factors for Health Promotion
  • Place of Presentation: Kyoto
  • Year and Date: 2007-11-27
• [Presentation] 親電子性物質のケミカルバイオロジー. 内因性および外因性因子の毒性発現にかかわる分子標的と生体応答を担うシステム (2007)
  • Author(s): 内田浩二
  • Organizer: 北陸大学学術フロンティアサテライトミーティング
  • Place of Presentation: 岐阜
  • Year and Date: 2007-07-27
• [Presentation] NGF作用増強因子 : NGF受容体活性化を指標にした食品成分の評価 (2007)
  • Author(s): 内田浩二
  • Organizer: 日本動物細胞工学会2007年度大会シンポジウム
  • Place of Presentation: 高崎
  • Year and Date: 2007-07-03
• [Presentation] 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 (2007)
  • Author(s): 内田浩二
  • Organizer: 第61回日本栄養食糧学会記念シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2007-05-19