Influences of phytochemicals on age- and disease-related degenerative neurons

• Project/Area Number: 21590225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Koshien University
• Principal Investigator: GOTOW Takahiro 甲子園大学, 栄養学部, 教授 (20135693)
• Co-Investigator(Kenkyū-buntansha): KOIKE Masato 順天堂大学, 医学研究科, 准教授 (80347210) ; SHIBATA Masahiro 新潟大学, 医歯学総合研究科, 准教授 (10343253)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: レスベラトロール / 老化促進マウス / PC12 細胞 / 肝細胞 / 活性酸素消去酵素 / 細 胞寿命関連タンパク質 / ミトコンドリア / オートファジー / PC12細胞 / サーチュインタンパク質 / AMPK活性化キナーゼ / LC3-I/II タンパク質 / LC3遺伝子ノックダウン / 神経細胞 / リポフスチン顆粒 / 細胞骨格タンパク質 / 細胞死関連タンパク質 / SIRT蛋白 / 細胞死関連蛋白 / キサントシン / 細胞骨格系 / 細胞死関連蛋白質

Research Abstract

We selected red wine polyphenol, resveratrol (RSV), among phytochemicals in this study, and analyzed its effects on neurons and hepatocytes in a neurodegeneration-related senescence-accelerated mouse P10 (SAMP10) and rat neuronal cell line (PC12 cells). When treated with RSV, in the SAMP10 degenerative neurons of the brain were significantly recovered, and as expected in the liver hepatocytes were much more improved. We analyzed more direct influence of RSV on the PC12 cell, and have proposed that RSV may promote cell survival by activations of mitochondria and autophagy.

Research Products

• [Journal Article] Resveratrol affects undifferentiated and differentiated PC12 cells differently, particularly with respect to possible differences in mitochondrial and autophagic fuctions (2013)
  • Author(s): Hyakawa N., Shiozaki M., Shibata M., Koike M., Uchiyama Y., Matsuura N., Gotow T.
  • Journal Title: Eur. J. Cell Biol Volume: 92 Issue: 1 Pages: 30-43
  • DOI: 10.1016/j.ejcb.2012.10.002
  • Peer Reviewed
• [Journal Article] Closer association of mitochondria with lipid droplets in hepatocytes and activation of Kupffer cells in resveratrol-treated senescence-accelerated mice (2011)
  • Author(s): Shiozaki M., Hayakawa N., Shibata M., Koike M., Uchiyama Y., Gotow T.
  • Journal Title: Histochem. Cell Biol Volume: 136 Issue: 4 Pages: 475-489
  • DOI: 10.1007/s00418-011-0847-6
  • Peer Reviewed
• [Journal Article] Neurofilament cross-bridge - A structure associated specifically with the neurofilament among the intermediate filament family. Chapter 10 in"Cytoskeleton of the Nervous System" (2011)
  • Author(s): Gotow T.
  • Journal Title: In Advances in Neurobiology Vol. 3, eds. R.A.Nixon, A. Yuan,Springer, New York Pages: 225-247
  • DOI: 10.1007/978-1-4419-6787-9_10
  • ISBN: 9781441967862, 9781441967879
• [Journal Article] Neurofilament cross-bridge-A structure associated specifically with the neurofilament among the intermediate filament family (2011)
  • Author(s): Takahiro Gotow
  • Journal Title: Advances in Neurobiology (Cytoskeleton of the Nervous System) Volume: 3 Pages: 225-247
• [Journal Article] Phosphorylation of highly conserved neurofilament medium KSP repeats is not required formyelin-dependent radial axonal growth (2009)
  • Author(s): Garcia M.L., Rao M.V., Fujimoto J.,Garcia V.B., Shah S.B., Crum J., Gotow T.,Uchiyama Y., Ellisman M., Calcutt N.A., Cleveland D.W.
  • Journal Title: J. Neurosci Volume: 29 Issue: 5 Pages: 1277-1284
  • DOI: 10.1523/jneurosci.3765-08.2009
  • Peer Reviewed
• [Journal Article] レスベラトロールの細胞機能及び細胞老化の改善効果 (2009)
  • Author(s): 塩崎元子、竹内翔一、早川直哉、後藤隆洋
  • Journal Title: トップフードテクノフォーカス(奥野製薬) Volume: 13 Pages: 1-20
  • URL: http://www.okuno.co.jp/technofocus/food_techno013.html
• [Journal Article] Very high dose α-tocopherol supplementation increases blood pressure and causes possible sdverse CNS effects instroke-prone spontaneously hypertensive rats (2009)
  • Author(s): Miyamoto K., Shiozaki M., Shibata M.,Koike, M., Uchiyama, Y., Gotow T.
  • Journal Title: J. Neurosci. Res Volume: 87 Issue: 2 Pages: 556-566
  • DOI: 10.1002/jnr.21851
  • Peer Reviewed
• [Journal Article] Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth (2009)
  • Author(s): Garcia M.L., Rao M.V., Fujimoto J., Garcia V.B., Shah S.B., Crum J., Gotow T., Uchiyama Y., Ellisman M., Calcutt N.A., Cleveland D.W.
  • Journal Title: Journal of Neuroscience 29 Pages: 1277-1284
  • Peer Reviewed
• [Journal Article] レスベラトロールの細胞機能及び細胞老化の改善効果 (2009)
  • Author(s): 塩崎元子、竹内翔一、早川直哉、後藤隆洋
  • Journal Title: トップフードテクノフォーカス(奥野製薬) 13 Pages: 1-20
• [Journal Article] Neurofilament cross-bridge : A structure associated specifically with the neurofilament among the intermediate filament family
  • Author(s): Gotow, T
  • Journal Title: Handbook of Neurochemistry and Molecular Neurobiology 14(in press)
• [Presentation] レスベラトロールによるミトコンドリア/オートファジー機能制御と細胞寿命との関係 (2013)
  • Author(s): 早川直哉、森本美幸、柴田昌宏、小池正人、内山安男、後藤隆洋
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 高松
  • Year and Date: 2013-03-28
• [Presentation] レスベラトロールの細胞生存及び細胞死の調節機構 (2012)
  • Author(s): 早川直哉、柴田昌宏、小池正人、内山安男、後藤隆洋
  • Organizer: 第88回日本解剖学会・近畿支部学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-01
• [Presentation] PC12 cells are influenced differently by resveratrol depending on their differentiation (2012)
  • Author(s): Hayakawa N., Shiozaki M., Shibata M., Koike M., Uchiyama Y., Gotow T.
  • Organizer: The 42nd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2012-10-18
• [Presentation] Resveratrol is harmful to naive PC12 cells but beneficial to differentiated ones (2012)
  • Author(s): Hayakawa N. , Shiozaki M. , Shibata M.Koike M. , Uchiyama Y. , Gotow T.
  • Organizer: The 35th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Nagoya
  • Year and Date: 2012-09-18
• [Presentation] レスベラトロールは老化促進マウス(SAMP10)肝細胞の脂肪滴を減少させミトコンドリアを増加させる (2011)
  • Author(s): 早川直哉、塩崎元子、柴田昌宏、小池正人、内山安男、後藤隆洋
  • Organizer: 第116回日本解剖学会総会・全国学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-30
• [Presentation] レスベラトロールは老化促進マウス(SAMP10)肝細胞の脂肪滴を減少させミトコンドリアを増加させる (2011)
  • Author(s): 早川直哉、塩崎元子、柴田昌宏、小池正人、内山安男、後藤隆洋
  • Organizer: 日本解剖学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-30
• [Presentation] Resveratrol is beneficial to senescence-accelerated mouse neurons and to differentiated but not naive PC12 cells (2009)
  • Author(s): Shiozaki M., Takeuchi S., Hayakawa N.,Shibata M., Koike M., Uchiyama Y., Gotow T.
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-10-22
• [Presentation] Resveratrol improves age-related changes in SAMP10 CNS (2009)
  • Author(s): Shiozaki M, Takeuchi S., Hayakawa, N.,Shibata M., Koike M., Uchiyama Y., Gotow T.
  • Organizer: The 32nd Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Nagoya
  • Year and Date: 2009-09-18
• [Presentation] Resveratrol is harmful to naive PC12 cells but beneficial to the differentiated ones (2009)
  • Author(s): Takeuchi S., Shiozaki M., Hayakawa N.,Shibata M., Koike M., Uchiyama Y., Gotow T.
  • Organizer: The 32nd Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Nagoya
  • Year and Date: 2009-09-17
• [Presentation] レスベラトロールはSAMP10の神経細胞及び肝細胞の老化関連変化を改善する (2009)
  • Author(s): 塩崎元子、竹内翔一、早川直哉、柴田昌宏、小池正人、内山安男、後藤隆洋
  • Organizer: 第114回日本解剖学会総会・全国学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-03-30
• [Presentation] レスベラトロールの未分化及び分化PC12細胞における影響 (2009)
  • Author(s): 竹内翔一、塩崎元子、早川直哉、柴田昌宏、小池正人、内山安男、後藤隆洋
  • Organizer: 第114回日本解剖学会総会・全国学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2009-03-30
• [Presentation] Resveratrol improves age-related changes in SAMP10 CNS (2009)
  • Author(s): Motoko Shiozaki, Shoichi Takeuchi, Naoya Hayakawa, Masahiro Shibata, Masato Koike, Yasuo Uchiyama, Takahiro Gotow
  • Organizer: The 32nd Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] Resveratrol is harmful to naive PC12 cells but beneficial to the differentiated ones (2009)
  • Author(s): Shoichi Takeuchi, Motoko Shiozaki, Naoya Hayakawa, Masahiro Shibata, Masato Koike, Yasuo Uchiyama, Takahiro Gotow
  • Organizer: The 32nd Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] Protective effects of xanthosine on ethanol-impaired neurons (2009)
  • Author(s): Naoya Hayakawa, Motoko Shiozaki, Shoichi Takeuchi, Masahiro Shibata, Masato Koike, Yasuo Uchiyama, Takahiro Gotow
  • Organizer: The 32nd Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] Resveratrol is beneficial to senescence-accelerated mouse neurons and to differentiated but not naive PC12 cells (2009)
  • Author(s): Motoko Shiozaki, Shoichi Takeuchi, Naoya Hayakawa, Masahiro Shibata, Masato Koike, Yasuo Uchiyama, Takahiro Gotow
  • Organizer: The 39th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: マコーミック会議場(Chicago, USA)
• [Presentation] Resveratrol is harmful to naive PC12 cells but beneficial to differentiated ones
  • Author(s): Hayakawa N.
  • Organizer: The 35th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 名古屋国際会議場（名古屋市中区）
• [Presentation] PC12 cells are influenced differently by resveratrol depending on their differentiation
  • Author(s): Hayakawa N.
  • Organizer: The 42nd Annual Meeting of the Society for Neuroscience
  • Place of Presentation: ERNEST N. MORIAL CONVENTION CENTER (New Orleans)
• [Presentation] レスベラトロールは未分化と分化PC12細胞で逆の作用を示す
  • Author(s): 早川直哉
  • Organizer: 第51回日本栄養・食糧学会・近畿支部大会
  • Place of Presentation: 甲子園大学（宝塚市）
• [Presentation] レスベラトロールの細胞生存及び細胞死の調節機構
  • Author(s): 早川直哉
  • Organizer: 第88回日本解剖学会・近畿支部学術集会
  • Place of Presentation: 神戸大学（神戸市）
• [Presentation] レスベラトロールによるミトコンドリア/オートファジー機能制御と細胞寿命との関係
  • Author(s): 早川直哉
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: サンポートホール高松・かがわ国際会議場（高松市）